Skip to main content
SpringerLink
Log in

Clinical Pharmacokinetic and Pharmacodynamic Properties of Drugs Used in the Treatment of Parkinson’s Disease

  • Review Article
  • Special Populations
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Current research in Parkinson’s disease (PD) focuses on symptomatic therapy and neuroprotective interventions. Drugs that have been used for symptomatic therapy are levodopa, usually combined with a peripheral decarboxylase inhibitor, synthetic dopamine receptor agonists, centrally-acting antimuscarinic drugs, amantadine, monoamine oxidase-B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors. Drugs for which there is at least some evidence for neuroprotective effect are certain dopamine agonists, amantadine and MAO-B inhibitors (selegiline).

Levodopa remains the most effective drug for the treatment of PD. Several factors contribute to the complex clinical pharmacokinetics of levodopa: erratic absorption, short half-life, peripheral O-methylation and facilitated transport across the blood-brain barrier. In patients with response fluctuations to levodopa, the concentration-effect curve becomes steeper and shifts to the right compared with patients with stable response. Pharmacokinetic-pharmacodynamic modelling can affect decisions regarding therapeutic strategies.

The dopamine agonists include ergot derivatives (bromocriptine, pergolide, lisuride and cabergoline), non-ergoline derivatives (pramipexole, ropinirole and piribedil) and apomorphine. Most dopamine agonists have their specific pharmacological profile. They are used in monotherapy and as an adjunct to levodopa in early and advanced PD.

Few pharmacokinetic and pharmacodynamic data are available regarding centrally acting antimuscarinic drugs. They are characterised by rapid absorption after oral intake, large volume of distribution and low clearance relative to hepatic blood flow, with extensive metabolism.

The mechanism of action of amantadine remains elusive. It is well absorbed and widely distributed. Since elimination is primarily by renal clearance, accumulation of the drug can occur in patients with renal dysfunction and dosage reduction must be envisaged.

The COMT inhibitors entacapone and tolcapone dose-dependently inhibit the formation of the major metabolite of levodopa, 3-O-methyldopa, and improve the bioavailability and reduce the clearance of levodopa without significantly affecting its absorption. They are useful adjuncts to levodopa in patients with end-of-dose fluctuations.

The MAO-B inhibitor selegiline may have a dual effect: reducing the catabolism of dopamine and limiting the formation of neurotoxic free radicals. The pharmacokinetics of selegiline are highly variable; it has low bioavailability and large volume of distribution. The oral clearance is many-fold higher than the hepatic blood flow and the drug is extensively metabolised into several metabolites, some of them being active.

Despite the introduction of several new drugs to the antiparkinsonian armamentarium, no single best treatment exists for an individual patient with PD. Particularly in the advanced stage of the disease, treatment should be individually tailored.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Table I
Fig. 4
Table II
Table III
Table IV
Table V
Table VI

Similar content being viewed by others

Notes

  1. Use of tradenames is for product identification only and does not imply endorsement.

References

  1. Weill E. De l’apomorphine dans certains troubles nerveux. Lyon Med 1884; 48: 411–9

    Google Scholar 

  2. Ehringer H, Hornykiewicz O. Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen der extrapyramidalen Systems. Klin Wochenschrift 1960; 38: 1236–9

    Article  CAS  Google Scholar 

  3. Cotzias GC, Van Woert MH, Schiffer LM. Aromatic amino acids and modification of parkinsonism. N Engl J Med 1967; 276: 374–9

    Article  PubMed  CAS  Google Scholar 

  4. Bartholini G, Burkard WF, Pletscher A, et al. Increase in cerebral catecholamines caused by 3,4-dihydroxyphenylalanine after inhibition of peripheral decarboxylase. Nature 1967; 215: 852–3

    Article  PubMed  CAS  Google Scholar 

  5. Deleu D, Hanssens Y. Current and emerging strategies in the management of Parkinson’s disease: a critical reappraisal. Saudi Med J 1997; 18: 115–26

    Google Scholar 

  6. Olanow CW, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease: treatment guidelines. American Academy of Neurology. Neurology 1998; 50 Suppl. 3:S1–57

    Article  PubMed  CAS  Google Scholar 

  7. Rabey JM, Vered Y, Shabtai H, et al. Improvement of parkinsonian features correlate with high plasma levodopa values after broad bean (Vicia faba) consumption. J Neurol Neurosurg Psychiatry 1992; 55: 725–7

    Article  PubMed  CAS  Google Scholar 

  8. Cedarbaum JM, Williamson R, Kutt H. Simultaneous determination of levodopa, its metabolites and carbidopa in clinical samples. J Chromatogr 1987; 415: 393–9

    Article  PubMed  CAS  Google Scholar 

  9. Deleu D, Sarre S, Ebinger G, et al. Simultaneous monitoring of levodopa, dopamine and their metabolites in skeletal muscle and subcutaneous tissue in different pharmacological conditions using microdialysis. J Pharm Biomed Anal 1993; 11: 577–85

    Article  PubMed  CAS  Google Scholar 

  10. Michotte Y, Deleu D, Ebinger G. The use of capillary gas chromatography/mass spectrometry for the determination of acidic dopamine metabolites in human brain. Biomed Mass Spect 1985; 12: 704–6

    Article  CAS  Google Scholar 

  11. Rondelli I, Acerbi D, Mariotti F, et al. Simultaneous determination of levodopa methyl ester, levodopa, 3-O-methyldopa and dopamine in plasma by high-performance liquid chromatography with electrochemical detection. J Chromatogr B Biomed Appl 1994; 653: 17–23

    Article  PubMed  CAS  Google Scholar 

  12. Rahman MK, Nagatsu T, Kato T. Aromatic L-amino acid decarboxylase activity in central and peripheral tissues and serum of rats with L-DOPA and L-5-hydroxytryptophan as substrates. Biochem Pharmacol 1981; 30: 645–9

    Article  PubMed  CAS  Google Scholar 

  13. Lovenberg W, Victor SJ. Regulation of tryptophan and tyrosine hydroxylase. Life Sci 1974; 14: 2337–53

    Article  PubMed  CAS  Google Scholar 

  14. Axelrod J. Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines. Pharmacol Rev 1966; 18: 95–113

    PubMed  CAS  Google Scholar 

  15. Nissinen E, Tuominen R, Perhoniemi V, et al. Catechol-O-methytransferase and aromatic L-amino acid decarboxylase activities in human gastrointestinal tissues. Life Sci 1991; 49: 721–5

    Article  Google Scholar 

  16. Abell CW. Monoamine oxidase A and B from human liver and brain. Methods Enzymol 1987; 142: 638–50

    Article  PubMed  CAS  Google Scholar 

  17. Benedetti MS, Dostert P. Commentary: monoamine oxidase, brain aging and degenerative disease. Biochem Pharmacol 1989; 38: 55–61

    Google Scholar 

  18. Saura J, Kettler R, Da Prada M, et al. Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19-6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain. J Neurosci 1992; 12: 1977–99

    PubMed  CAS  Google Scholar 

  19. Kaakkola S. Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson’s disease. Drugs 2000; 59: 1233–50

    Article  PubMed  CAS  Google Scholar 

  20. Cedarbaum JM, Kutt H, McDowell FH. Clinical significance of the relationship between O-methyldopa levels and levodopa intake. Neurology 1988; 21: 533–6

    Article  Google Scholar 

  21. Alexander GM, Schwartzman RJ, Grothusen JR, et al. Effect of plasma levels of large neutral amino acids and degree of parkinsonism on the blood-to-brain transport of levodopa in naïve and MPTP parkinsonian monkeys. Neurology 1994; 44: 1491–9

    Article  PubMed  CAS  Google Scholar 

  22. Sandler M, Johnson RD, Ruthven CR, et al. Transamination is a major pathway of L-dopa metabolism following peripheral decarboxylase inhibition. Nature 1974; 247: 364–6

    Article  PubMed  CAS  Google Scholar 

  23. Olanow CW, Gauger LL, Cedarbaum JM. Temporal relationship between plasma and cerebrospinal fluid pharmacokinetics and clinical effect in Parkinson’s disease. Ann Neurol 1991; 29: 556–9

    Article  PubMed  CAS  Google Scholar 

  24. Goodall MC, Alton H. Metabolism of 3,4-dihydroxyphenylalanine (L-dopa) in human subjects. Biochem Pharmacol 1972; 21: 2401–8

    Article  PubMed  CAS  Google Scholar 

  25. Da Prada M, Kettler R, Zurcher G, et al. Inhibition of decarboxylase and levels of dopa and 3-O-methyldopa: a comparative study of benserazide versus carbidopa in rodents and of Madopar standard versus Madopar HBS in volunteers. Eur Neurol 1987; 27 Suppl. 1: 9–20

    Article  PubMed  Google Scholar 

  26. Kaakkola S, Mannisto PT, Nissinen E, et al. The effect of an increased ratio of carbidopa to levodopa on the pharmacokinetics of levodopa. Acta Neurol Scand 1985; 72: 385–91

    Article  PubMed  CAS  Google Scholar 

  27. Cedarbaum JM. Clinical pharmacokinetics of anti-parkinsonian drugs. Clin Pharmacokinet 1987; 13: 141–78

    Article  PubMed  CAS  Google Scholar 

  28. Aoki FY, Sitar DS. Clinical pharmacokinetics of amantadme hydrochloride. Clin Pharmacokinet 1988; 14: 35–51

    Article  PubMed  CAS  Google Scholar 

  29. Horadam VW, Sharp JG, Smilack JD, et al. Pharmacokinetics of amantadme hydrochloride in subjects with normal and impaired renal function. Ann Int Med 1981; 94: 454–8

    PubMed  CAS  Google Scholar 

  30. Nutt JG, Woodward WR, Anderson JL. The effect of carbidopa on the pharmacokinetics of intravenously administered levodopa: the mechanism of action in the treatment of parkinsonism. Ann Neurol 1985; 18: 537–43

    Article  PubMed  CAS  Google Scholar 

  31. Wade DN, Mearrick PT, Morris JL. Active transport of L-dopa in the intestine. Nature 1973; 242: 463–5

    Article  PubMed  CAS  Google Scholar 

  32. Robertson DRC, Renwick AG, Wood ND, et al. The influence of levodopa on gastric emptying in man. Br J Clin Pharmacol 1990; 29: 47–53

    Article  PubMed  CAS  Google Scholar 

  33. Contin M, Riva R, Martinelli P, et al. Effect of age on the pharmacokinetics of oral levodopa in patients with Parkinson’s disease. Eur J Clin Pharmacol 1991; 41: 463–6

    Article  PubMed  CAS  Google Scholar 

  34. Evans MA, Triggs EJ, Broe GA, et al. Systemic activity of orally administered L-dopa in the elderly Parkinson patient. Eur J Clin Pharmacol 1980; 17: 215–21

    Article  PubMed  CAS  Google Scholar 

  35. Baruzzi A, Contin M, Riva R, et al. Influence of meal ingestion time on pharmacokinetics of orally administered levodopa in Parkinsonian patients. Clin Neuropharmacol 1987; 10: 527–37

    Article  PubMed  CAS  Google Scholar 

  36. Pfeiffer RF. Antiparkinsonian agents: drug interactions of clinical significance. Drug Safety 1996; 14: 343–54

    Article  PubMed  CAS  Google Scholar 

  37. Astarloa R, Mena MA, Sanchez V, et al. Clinical and pharmacokinetic effects of a diet rich in insoluble fiber on Parkinson’s disease. Clin Neuropharmacol 1992; 15: 375–80

    Article  PubMed  CAS  Google Scholar 

  38. Neira WD, Sanchez V, Mena MA, et al. The effects of cisapride on L-dopa levels and clinical response in Parkinson’s disease. Mov Disord 1995; 10: 66–70

    Article  PubMed  CAS  Google Scholar 

  39. Reuter I, Harder S, Engelhardt M, et al. The effect of exercise on pharmacokinetics and pharmacodynamics of levodopa. Mov Disord 2000; 15: 862–8

    Article  PubMed  CAS  Google Scholar 

  40. Gancher ST, Nutt JG, Woodward WR. Peripheral pharmacokinetics of levodopa in untreated, stable and fluctuating Parkinsonian patients. Neurology 1987; 37: 940–4

    Article  PubMed  CAS  Google Scholar 

  41. Fabbrini G, Juncos J, Mouradian MM, et al. Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson’s disease. Ann Neurol 1987; 21: 370–6

    Article  PubMed  CAS  Google Scholar 

  42. Chase TN, Mouradian MM, Fabbrini G, et al. Pathogenetic studies of motor fluctuations in Parkinson’s disease. J Neural Transm Suppl 1988; 27: 3–10

    PubMed  CAS  Google Scholar 

  43. Pincus JH, Barry KM. Plasma levels of amino acids correlate with motor fluctuations in parkinsonism. Arch Neurol 1987; 44: 1006–9

    Article  PubMed  CAS  Google Scholar 

  44. Frankel JP, Kempster PA, Bovingdon M, et al. The effects of oral protein on the absorption of intraduodenal levodopa and motor performance. J Neurol Neurosurg Psychiatry 1989; 52: 1063–7

    Article  PubMed  CAS  Google Scholar 

  45. Nutt JG, Woodward WR, Carter JH, et al. Influence of fluctuations of plasma large neutral amino acids with normal diets on the clinical response to levodopa. J Neurol Neurosurg Psychiatry 1989; 52: 481–7

    Article  PubMed  CAS  Google Scholar 

  46. Karstaedt PJ, Pincus JH. Protein redistribution diet remains effective in patients with fluctuating parkinsonism. Arch Neurol 1992; 49: 149–51

    Article  PubMed  CAS  Google Scholar 

  47. Hammerstad JP, Woodward WR, Gliessman P, et al. L-dopa Pharmacokinetics in plasma and cisternal and lumbar cerebrospinal fluid of monkeys. Ann Neurol 1990; 27: 495–9

    Article  PubMed  CAS  Google Scholar 

  48. Cedarbaum JM, Olanow TI. Dopamine sulfate in ventricular cerebrospinal fluid and motor function in Parkinson’s disease. Neurology 1991; 41: 1567–70

    Article  PubMed  CAS  Google Scholar 

  49. Tyce GM, Ahlskog JE, Carmichael SW, et al. Catecholamines in CSF, plasma and, tissue after autologous transplantation of adrenal medulla to the brain in patients with Parkinson’s disease. J Lab Clin Med 1989; 114: 185–92

    PubMed  CAS  Google Scholar 

  50. Tohgi H, Abe T, Kikuchi T, et al. The significance of 3-O-methyldopa concentrations in the cerebrospinal fluid in the pathogenesis of wearing-off phenomenon in Parkinson’s disease. Neurosci Lett 1991; 132: 19–22

    Article  PubMed  CAS  Google Scholar 

  51. Tohgi H, Abe T, Takahashi S, et al. Alterations in the concentration of serotonergic and dopaminergic substances in the cerebrospinal fluid of patients with Parkinson’s disease, and their changes after L-dopa administration. Neurosci Lett 1993; 159: 135–8

    Article  PubMed  CAS  Google Scholar 

  52. Deleu D, Sarre S, Ebinger G, et al. The effect of carbidopa and entacapone pretreatment on the L-dopa pharmacokinetics and metabolism of blood plasma and skeletal muscle in beagle dog: an in vivo microdialysis study. J Pharmacol Exp Ther 1995; 273: 1323–31

    PubMed  CAS  Google Scholar 

  53. Nutt JG, Holford NHG. The response to levodopa in Parkinson’s disease: imposing pharmacological law and order. Ann Neurol 1996; 39: 561–73

    Article  PubMed  CAS  Google Scholar 

  54. Frankel JP, Pirtosek Z, Kempster PA, et al. Diurnal differences in response to oral levodopa. J Neurol Neurosurg Psychiatry 1990; 53: 948–50

    Article  PubMed  CAS  Google Scholar 

  55. Contin M, Riva R, Martinelli P, et al. Longitudinal monitoring of the levodopa concentration-effect relationship in Parkinson’s disease. Neurology 1994; 44: 1287–92

    Article  PubMed  CAS  Google Scholar 

  56. Durso R, Isaac K, Perry L, et al. Age influences magnitude but not duration of response to levodopa. J Neurol Neurosurg Psychiatry 1993; 56: 65–8

    Article  PubMed  CAS  Google Scholar 

  57. Harder S, Baas H, Rietbrock S. Concentration-effect relationship of levodopa in patients with Parkinson’s disease. Clin Pharmacokinet 1995; 29: 243–56

    Article  PubMed  CAS  Google Scholar 

  58. Contin M, Riva R, Martinelli P, et al. Relationship between levodopa concentration, dyskinesias, and motor effect in parkinsonian patients: a 3-year follow-up study. Clin Neuropharmacol 1997; 20: 409–18

    Article  PubMed  CAS  Google Scholar 

  59. Triggs EJ, Charles BG, Contin M, et al. Population pharmacokinetics and pharmacodynamics of oral levodopa in parkinsonian patients. Eur J Clin Pharmacol 1996; 51: 59–67

    Article  PubMed  CAS  Google Scholar 

  60. Contin M, Riva R, Martinelli P, et al. A levodopa kinetic-dynamic study of the rate of progression in Parkinson’s disease. Neurology 1998; 51: 1075–80

    Article  PubMed  CAS  Google Scholar 

  61. Gancher ST, Nutt JG, Woodward W. Response to brief levodopa infusions in parkinsonian patients with and without motor fluctuations. Neurology 1988; 38: 712–6

    Article  PubMed  CAS  Google Scholar 

  62. Zappia M, Colao R, Montesanti R, et al. Long-duration response to levodopa influences the pharmacodynamics of short duration response in Parkinson’s disease. Ann Neurol 1997; 42: 245–8

    Article  PubMed  CAS  Google Scholar 

  63. Zappia M, Bosco D, Piastino M, et al. Pharmacodynamics of the long-duration response to levodopa in PD. Neurology 1999; 53: 557–60

    Article  PubMed  CAS  Google Scholar 

  64. Barbato L, Stocchi F, Monge A, et al. The long-duration action of levodopa may be due to a postsynaptic effect. Clin Neuropharmacol 1997; 20: 394–401

    Article  PubMed  CAS  Google Scholar 

  65. Paalzow GHM, Paalzow LK. L-dopa: how it may exacerbate parkinsonian symptoms. Trends Pharmacol Sci 1986; 9: 15–9

    Article  Google Scholar 

  66. Mouradian MM, Heuser IJ, Baronti F, et al. Pathogenesis of dyskinesias in Parkinson’s disease. Ann Neurol 1989; 25: 523–6

    Article  PubMed  CAS  Google Scholar 

  67. Grahnén A, Eckernäs SA, Collin C, et al. Comparative multiple-dose pharmacokinetics of controlled-release levodopa products. Eur Neurol 1992; 32: 343–8

    Article  PubMed  Google Scholar 

  68. Poewe WH, Lees AJ, Stern GM. Clinical and pharmacokinetic observations with Madopar HBS in hospitalized patients with Parkinson’s disease and motor fluctuations. Eur Neurol 1987; 27 Suppl. 1: 93–7

    PubMed  Google Scholar 

  69. Cedarbaum JM. The promise and limitations of controlled-release oral levodopa administration. Clin Neuropharmacol 1989; 12: 147–66

    Article  PubMed  CAS  Google Scholar 

  70. Deleu D, Jacques M, Michotte Y, et al. Controlled-release levodopa/carbidopa (CR-4) in parkinsonian patients with response fluctuations on standard levodopa treatment: clinical and pharmacokinetic observations. Neurology 1989; 39 Suppl. 2: 88–92

    PubMed  CAS  Google Scholar 

  71. Lewitt PA. Clinical studies with and pharmacokinetic considerations of sustained-release levodopa. Neurology 1992; 42 Suppl. 1: 29–32

    Article  PubMed  CAS  Google Scholar 

  72. Dupont E, Andersen A, Boas J, et al. Sustained-release Madopar HBS compared with standard Madopar in the long-term treatment of de novo parkinsonian patients. Acta Neurol Scand 1996; 93: 14–20

    Article  PubMed  CAS  Google Scholar 

  73. Koller WC, Hutton JT, Tolosa E, et al. Immediate-release and controlled-release carbidiopa/levodopa in PD: a 5-year randomized multicenter study. Neurology 1999; 53: 1012–9

    Article  PubMed  CAS  Google Scholar 

  74. Gasser UE, Crevoisier C, Ouwerkerk M, et al. Comparative single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following a new dual-release and a conventional slow-relase formulation of levodopa and benserazide in healthy subjects. Eur J Pharm Biopharm 1998; 46: 223–8

    Article  PubMed  CAS  Google Scholar 

  75. Nutt JG, Carter JH, Woodward W, et al. Does tolerance develop to levodopa? Comparison of 2- and 21 -H levodopa infusions. MovDisord 1993; 8: 139–43

    Article  CAS  Google Scholar 

  76. Juncos JL, Mouradian MM, Fabbrini G, et al. Levodopa infusion therapy. In: Koller WC, Paulson G, editors. Therapy of Parkinson’s disease. New York: Marcel-Dekker, 1990: 185–201

    Google Scholar 

  77. Deleu D, Ebinger G, Michotte Y Clinical and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson’s disease with a fluctuating response to levodopa. Eur J Clin Pharmacol 1991; 41: 453–8

    Article  PubMed  CAS  Google Scholar 

  78. Kurth MC, Tetrud JW, Tanner CM, et al. Double-blind, placebocontrolled, crossover study of duodenal infusion of levodopa/carbidopa in Parkinson’s disease patients with ‘on-off’ fluctuations. Neurology 1993; 43: 1698–703

    Article  PubMed  CAS  Google Scholar 

  79. Kaye CM, Nicholls B. Clinical pharmacokinetics of ropinirole. Clin Pharmacokinet 2000; 39: 243–54

    Article  PubMed  CAS  Google Scholar 

  80. Heinonen EH, Myllyla V. Safety of selegiline (deprenyl) in the treatment of Parkinson’s disease. Drug Saf 1998; 19(1): 11–22

    Article  PubMed  CAS  Google Scholar 

  81. Melamed E, Offen D, Shirvan A, et al. Levodopa toxicity and apoptosis. Ann Neurol 1998; 44 Suppl. 1: S149–54

    PubMed  CAS  Google Scholar 

  82. Agid Y Levodopa: is toxicity a myth? Neurology 1998; 50: 858–63

    Article  PubMed  CAS  Google Scholar 

  83. Cedarbaum JM, Gandy SE, McDowell FH. ‘Early’ initiation of levodopa treatment does not promote the development of motor response fluctuations, dyskinesias, or dementia in Parkinson’s disease. Neurology 1991; 41: 622–9

    Article  PubMed  CAS  Google Scholar 

  84. Markham CH, Diamond SG. Long-term follow-up of early dopa treatment in Parkinson’s disease. Ann Neurol 1986; 19: 365–72

    Article  PubMed  CAS  Google Scholar 

  85. Stocchi F, Ruggieri S, Carta A, et al. Intravenous boluses and continuous infusions of L-dopa methyl ester in fluctuating patients with Parkinson’s disease. Mov Disord 1992; 7: 249–56

    Article  PubMed  CAS  Google Scholar 

  86. Steiger MJ, Stocchi F, Carta A, et al. The clinical efficacy of oral levodopa methyl ester solution in reversing afternoon ‘off’ periods in Parkinson’s disease. Clin Neuropharmacol 1991; 14: 241–4

    Article  PubMed  CAS  Google Scholar 

  87. Djaldetti R, Melamed E. Levodopa ethylester: a novel rescue therapy for response fluctuations in Parkinson’s disease. Ann Neurol 1996; 39: 400–4

    Article  PubMed  CAS  Google Scholar 

  88. Vallone D, Picetti R, Borrelli E. Structure and function of dopamine receptors. Neurosci Biobehav Rev 2000; 24: 125–32

    Article  PubMed  CAS  Google Scholar 

  89. Robertson GS, Robertson HA. Synergistic effects of D1 and D2 dopamine agonists on turning behaviour in rats. Brain Res 1986; 384: 387–90

    Article  PubMed  CAS  Google Scholar 

  90. Bedard PJ, Blanchet PJ, Levesque D, et al. Pathophysiology of L-dopa-induced dyskinesias. MovDisord 1999; 14 Suppl. 1: 4–8

    Google Scholar 

  91. Lange KW. Clinical pharmacology of dopamine agonists in Parkinson’s disease. Drugs Aging 1998; 13: 381–9

    Article  PubMed  CAS  Google Scholar 

  92. Lange KW, Rausch WD, Gsell W, et al. Neuroprotection by dopamine agonists. J Neural Transm Suppl. 1994; 43: 183–201

    PubMed  CAS  Google Scholar 

  93. Iida M, Miyazaki I, Tanaka K, et al. Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist. Brain Res 1999; 838: 51–9

    Article  PubMed  CAS  Google Scholar 

  94. Zou L, Jankovic J, Rowe DB, et al. Neuroprotection by pramipexole against dopamine- and levodopa-induced cytotoxicity. Life Sci 1999; 64: 1275–85

    Article  PubMed  CAS  Google Scholar 

  95. Grünblatt E, Mandel S, Berkuzki T, et al. Apomorphine protects against MPTP-induced neurotoxicity in mice. Mov Disord 1999; 14: 612–8

    Article  PubMed  Google Scholar 

  96. Gancher ST, Woodward WR, Boucher B, et al. Peripheral pharmacokinetics of apomorphine in humans. Ann Neurol 1989; 26: 232–8

    Article  PubMed  CAS  Google Scholar 

  97. Gancher ST, Nutt JG, Woodward WR. Absorption of apomorphine by various routes in parkinsonism. Mov Disord 1991; 6: 212–6

    Article  PubMed  CAS  Google Scholar 

  98. Friis ML, Gron U, Larsen NE, et al. Pharmacokinetics of bromocriptine during continuous oral treatment of Parkinson’s disease. Eur J Clin Pharmacol 1979; 15: 275–80

    Article  PubMed  CAS  Google Scholar 

  99. Andreotti AC, Pianezzola E, Persiani S, et al. Pharmacokinetics, pharmacodynamics, and tolerability of cabergoline, a prolactin-lowering drug, after administration of increasing oral doses (0.5, 1.0, and 1.5 milligrams) in healthy male volunteers. J Clin Endocrinol Metab 1995; 80: 841–5

    Article  PubMed  CAS  Google Scholar 

  100. Burns RS, Gopinathan G, Humpel M, et al. Disposition of oral lisuride in Parkinson’s disease. Clin Pharmacol Ther 1984; 35: 548–56

    Article  PubMed  CAS  Google Scholar 

  101. Langtry HD, Clissold SP. Pergolide: a review of its pharmacological properties and therapeutic potential in Parkinson’s disease. Drugs 1990; 39: 491–506

    Article  PubMed  CAS  Google Scholar 

  102. Jenner P. Parkinson’s disease: pathological mechanisms and actions of piribedil. J Neurol 1992; 239 Suppl. 1: S2–8

    PubMed  Google Scholar 

  103. Bennett Jr JP, Piercey MF. Pramipexole: a new dopamine agonist for the treatment of Parkinson’s disease. J Neurol Sci 1999; 163: 25–31

    Article  PubMed  CAS  Google Scholar 

  104. Bowsher RR, Apathy JM, Compton JA, et al. Sensitive, specific radioimmunoassay for quantifying pergolide in plasma. Clin Chem 1992; 38: 1975–80

    PubMed  CAS  Google Scholar 

  105. Haring N, Salarna Z, Jaeger H. Triple stage quadrupole mass spectrometric determination of bromocriptine in human plasma with negative ion chemical ionization. Arzneimittelfors 1988; 38: 1529–32

    CAS  Google Scholar 

  106. Phelan DG, Greig NH, Rapoport SI, et al. High-performance liquid Chromatographic assay of bromocriptine in rat plasma and brain. J Chromatogr 1990; 533: 264–70

    Article  PubMed  CAS  Google Scholar 

  107. Wolthers BG, Verhagen Kamerbeek WD, van Beusekom CM, et al. Quantitative determination of the dopamine agonist lisuride in plasma using high-performance liquid chromatography with fluorescence detection. J Chromatogr 1993; 622: 33–8

    Article  PubMed  CAS  Google Scholar 

  108. Beattie IG, Blake TJ. Application of thermospray liquid chroma-tography-mass spectrometry and liquid chromatography-tandem mass spectrometry for the identification of cynomolgus monkey and human metabolites of SK & F 101468, a dopamine D2 receptor agonist. J Chromatogr 1989; 474: 123–38

    Article  PubMed  CAS  Google Scholar 

  109. Lau YY, Hanson GD, Ichhpurani N. Determination of pramipexole (U-98,528) in human plasma and urine by high-performance liquid chromatography with electrochemical and ultraviolet detection. J Chromatogr B Biomed Appl 1996; 683: 217–23

    Article  PubMed  CAS  Google Scholar 

  110. Pianezzola E, Bellotti V, La Croix R, et al. Determination of cabergoline in plasma and urine by high-performance liquid chromatography with electrochemical detection. J Chromatogr 1992; 574: 170–4

    Article  PubMed  CAS  Google Scholar 

  111. Sarati S, Guiso G, Spinelli R, et al. Determination of piribedil and its basic metabolites in plasma by high-performance liquid chromatography. J Chromatogr 1991; 563: 323–32

    Article  PubMed  CAS  Google Scholar 

  112. Friis ML, Paulson OB, Hertz MM. Transfer of bromocriptine across the blood-brain barrier in man. Acta Neurol Scand 1979; 59: 88–95

    Article  PubMed  CAS  Google Scholar 

  113. Lieberman AN, Goldstein M. Bromocriptine in Parkinson’s disease. Pharmacol Rev 1985; 37: 217–27

    PubMed  CAS  Google Scholar 

  114. Parkinson’s Disease Research Group in the United Kingdom. Comparisons of therapeutic effects of levodopa, levodopa and selegiline, and bromocriptine in patients with early, mild Parkinsons disease: three year interim report. BMJ 1993; 307: 469–72

    Article  Google Scholar 

  115. Hely MA, Morris JG, Reid WG, et al. The Sydney Multicentre Study of Parkinson’s disease: a randomised, prospective five year study comparing low dose bromocriptine with low dose levodopa-carbidopa. J Neurol Neurosurg Psychiatry 1994; 57: 903–10

    Article  PubMed  CAS  Google Scholar 

  116. Montastruc JL, Rascol O, Senard JM, et al. A randomised controlled study comparing bromocriptine to which levodopa was later added, with levodopa alone in previously untreated patients with Parkinson’s disease: a five year follow up. J Neurol Neurosurg Psychiatry 1994; 57: 1034–8

    Article  PubMed  CAS  Google Scholar 

  117. Weiner WJ, Factor SA, Sanchez-Ramos JR, et al. Early combination therapy (bromocriptine and levodopa) does not prevent motor fluctuations in Parkinson’s disease. Neurology 1993; 43: 21–7

    Article  PubMed  CAS  Google Scholar 

  118. Parkes D. Drug therapy: bromocriptine. N Engl J Med 1979; 301: 873–8

    Article  PubMed  CAS  Google Scholar 

  119. Hely MA, Morris JG, Lawrence S, et al. Retroperitoneal fibrosis, skin and pleuropulmonary changes associated with bromocriptine therapy. Aust N Z J Med 1991; 21: 82–4

    Article  PubMed  CAS  Google Scholar 

  120. Ayres J, Maisey MN. Alcohol increases bromocriptine’s side effects [letter]. N Engl J Med 1980; 302: 806

    Article  PubMed  CAS  Google Scholar 

  121. Wynalda MA, Wienkers LC. Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos 1997; 25: 1211–4

    PubMed  CAS  Google Scholar 

  122. Rubin A, Lemberger L, Dhahir P. Physiologic disposition of pergolide. Clin Pharmacol Ther 1981; 30: 258–65

    Article  PubMed  CAS  Google Scholar 

  123. Barone P, Bravi D, Bermejo-Pareja F, et al. Pergolide monotherapy in the treatment of early PD: a randomized, controlled study. Pergolide Monotherapy Study Group. Neurology 1999; 53: 573–9

    Article  PubMed  CAS  Google Scholar 

  124. Kulisevsky J, Lopez-Villegas D, Garcia-Sanchez C, et al. A six-month study of pergolide and levodopa in de novo Parkinson’s disease patients. Clin Neuropharmacol 1998; 21: 358–62

    PubMed  CAS  Google Scholar 

  125. Wolters EC, Tissingh G, Bergmans PL, et al. Dopamine agonists in Parkinson’s disease. Neurology 1995; 45 Suppl. 3: S28–34

    Article  PubMed  CAS  Google Scholar 

  126. Rinne UK. Lisuride, a dopamine agonists in the treatment of early Parkinson’s disease. Neurology 1983; 39: 336–9

    Article  Google Scholar 

  127. Shannon KM, Bennett JP Jr, Friedman JH. Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson’s disease. The Pramipexole Study Group. Neurology 1997; 49: 724–8

    Article  PubMed  CAS  Google Scholar 

  128. Rascol O, Brooks DJ, Korczyn AD, et al. A five-year study of the incidence of dyskinesia in patients with early Parkinson’s disease who were treated with ropinirole or levodopa. 056 Study Group. N Engl J Med 2000; 342: 1484–91

    Article  PubMed  CAS  Google Scholar 

  129. Rinne UK, Bracco F, Chouza C, et al. Early treatment of Parkinson’s disease with cabergoline delays the onset of motor complications: results of a double-blind levodopa controlled trial. The PKDS009 Study Group. Drugs 1998; 55 Suppl. 1: 23–30

    Article  PubMed  CAS  Google Scholar 

  130. Ziegler M, Lacomblez L, Rascol O, et al. Efficacy of piribedil in adjunction to L-dopa in a six-month randomized placebo controlled study in early Parkinson’s disease [abstract]. Neurology 2000; 45 Suppl. 3: A280

    Google Scholar 

  131. Guttman M. Double-blind comparison of pramipexole and bromocriptine treatment with placebo in advanced Parkinson’s disease. International Pramipexole-Bromocriptine Study Group. Neurology 1997; 49: 1060–5

    Article  PubMed  CAS  Google Scholar 

  132. Olanow CW, Fahn S, Muenter M, et al. A multicenter doubleblind placebo-controlled trial of pergolide as an adjunct to Sinemet in Parkinson’s disease. Mov Disord 1994; 9: 40–7

    Article  PubMed  CAS  Google Scholar 

  133. Lieberman AN, Goldstein M, Leibowitz M, et al. Lisuride combined with levodopa in advanced Parkinson disease. Neurology 1981; 31: 1466–9

    Article  PubMed  CAS  Google Scholar 

  134. Lieberman A, Ranhosky A, Korts D. Clinical evaluation of pramipexole in advanced Parkinson’s disease: results of a double-blind, placebo-controlled, parallel-group study. Neurology 1997; 49: 162–8

    Article  PubMed  CAS  Google Scholar 

  135. Lieberman A, Olanow CW, Sethi K, et al. A multicenter trial of ropinirole as adjunct treatment for Parkinson’s disease. Ropinirole Study Group. Neurology 1998; 51: 1057–62

    Article  PubMed  CAS  Google Scholar 

  136. Hutton JT, Koller WC, Ahlskog JE, et al. Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson’s disease. Neurology 1996; 46: 1062–5

    Article  PubMed  CAS  Google Scholar 

  137. Jankovic J. Long-term study of pergolide in Parkinson’s disease. Neurology 1985; 35: 296–9

    Article  PubMed  CAS  Google Scholar 

  138. Tanner CM, Goetz CG, Glantz RH, et al. Pergolide mesylate: four years experience in Parkinson’s disease. Adv Neurol 1987; 45: 547–9

    PubMed  CAS  Google Scholar 

  139. Lieberman AN, Neophytides A, Leibowitz M, et al. Comparative efficacy of pergolide and bromocriptine in patients with advanced Parkinson’s disease. Adv Neurol 1983; 37: 95–108

    PubMed  CAS  Google Scholar 

  140. Le Witt PA, Ward CD, Larsen TA, et al. Comparison of pergolide and bromocriptine therapy in parkinsonism. Neurology 1983; 33: 1009–14

    Article  Google Scholar 

  141. Goetz CG, Tanner CM, Glantz RH, et al. Chronic agonist therapy for Parkinson’s disease: a 5-year study of bromocriptine and pergolide. Neurology 1985; 35: 749–51

    Article  PubMed  CAS  Google Scholar 

  142. Goetz CG, Shannon KM, Tanner CM, et al. Agonist substitution in advanced Parkinson’s disease. Neurology 1989; 39: 1121–2

    Article  PubMed  CAS  Google Scholar 

  143. Clarke CE, Speller JM. Pergolide versus bromocriptine for levodopa-induced motor complications in Parkinson’s disease. The Cochrane Database of Systematic Reviews. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; Issue 2. Oxford: Update Software, 2000, CD000236

    Google Scholar 

  144. Kurlan R, Miller C, Knapp R, et al. Double-blind assessment of potential pergolide-induced cardiotoxicity. Neurology 1986; 36: 993–5

    Article  PubMed  CAS  Google Scholar 

  145. Kando JC, Keck Jr PE, Wood PA. Pergolide-induced hypotension [letter]. DICP 1990; 24: 543

    PubMed  CAS  Google Scholar 

  146. Wachtel H. Antiparkinsonian dopamine agonists: a review of the pharmacokinetics and neuropharmacology in animals and humans. J Neural Transm Park Dis Dement Sect 1991; 3: 151–201

    Article  PubMed  CAS  Google Scholar 

  147. Obeso JA, Luquin MR, Martinez-Lage JM. Lisuride infusion pump: a device for the treatment of motor fluctuations in Parkinson’s disease. Lancet 1986; 1: 467–70

    Article  PubMed  CAS  Google Scholar 

  148. Nomoto M, Iwata S, Irifune M, et al. Dermal application of lisuride on parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset and on cases with Parkinson’s disease. Nihon Shinkei Seishin Yakurigaku Zasshi 1998; 18: 81–7

    PubMed  CAS  Google Scholar 

  149. Humpel M, Nieuweboer B, Hasan SH, et al. Radioimmunoassay of plasma lisuride in man following intravenous and oral administration of lisuride hydrogen maleate: effect on plasma prolactin level. Eur J Clin Pharmacol 1981; 20: 47–51

    Article  PubMed  CAS  Google Scholar 

  150. Rinne UK. Combination therapy with lisuride and L-dopa in the early stages of Parkinson’s disease decreases and delays the development of motor fluctuations: long-term study over 10 years in comparison with L-dopa monotherapy. Nervenarzt 1999; 70 Suppl. 1: S19–25

    Article  PubMed  Google Scholar 

  151. Obeso JA, Luquin MR, Martinez Lage JM. Intravenous lisuride corrects oscillations of motor performance in Parkinson’s disease. Ann Neurol 1986; 19: 31–5

    Article  PubMed  CAS  Google Scholar 

  152. Laihinen A, Rinne UK, Suchy I. Comparison of lisuride and bromocriptine in the treatment of advanced Parkinson’s disease. Acta Neurol Scand 1992; 86: 593–5

    Article  PubMed  CAS  Google Scholar 

  153. Lieberman AN, Gopinathan G, Neophytides A, et al. Pergolide and lisuride in advanced Parkinson’s disease. Adv Neurol 1984; 40: 503–7

    PubMed  CAS  Google Scholar 

  154. Vaamonde J, Luquin MR, Obeso JA. Subcutaneous lisuride infusion in Parkinson’s disease: response to chronic administration in 34 patients. Brain 1991; 114: 601–17

    Article  PubMed  Google Scholar 

  155. Capria A, Attanasio A, Quatrana M, et al. Cardiovascular effects of lisuride continuous intravenous infusion in fluctuating Parkinson’s disease. Clin Neuropharmacol 1989; 12: 331–8

    Article  PubMed  CAS  Google Scholar 

  156. Lees AJ. Dopamine agonists in Parkinson’s disease: a look at apomorphine. Fundam Clin Pharmacol 1993; 7: 121–8

    Article  PubMed  CAS  Google Scholar 

  157. Cotzias GC, Lawrence WH, Papavasiliou PS, et al. Apomorphine and parkinsonism. Trans Amer Neurol Assoc 1972; 97: 156–9

    Google Scholar 

  158. Hardie RJ, Lees AJ, Stern GM. On-off fluctuations in Parkinson’s disease: a clinical and neuropharmacological study. Brain 1984; 107: 487–506

    Article  PubMed  Google Scholar 

  159. Kapoor R, Turjanski N, Frankel J, et al. Intranasal apomorphine: a new treatment in Parkinson’s disease [letter]. J Neurol Neurosurg Psychiatry 1990; 53: 1015

    Article  PubMed  CAS  Google Scholar 

  160. Lees AJ, Montastruc JL, Turjanski N, et al. Sublingual apomorphine and Parkinson’s disease [letter]. J Neurol Neurosurg Psychiatry 1989; 52: 1440

    Article  PubMed  CAS  Google Scholar 

  161. Frankel JP, Lees AJ, Kempster PA, et al. Subcutaneous apomorphine in the treatment of Parkinson’s disease. J Neurol Neurosurg Psychiatry 1990; 53: 96–101

    Article  PubMed  CAS  Google Scholar 

  162. Poewe W, Kleedorfer B, Gerstenbrand F, et al. Subcutaneous apomorphine in Parkinson’s disease [letter]. Lancet 1988; I: 943

    Article  Google Scholar 

  163. Hughes AJ, Bishop S, Kleedorfer B, et al. Subcutaneous apomorphine in Parkinson’s disease: response to chronic administration for up to five years. Mov Disord 1993; 8: 165–70

    Article  PubMed  CAS  Google Scholar 

  164. Ellis CM, Lemmens G, Parkes JD. Use of apomorphine in parkinsonian patients with neuropsychiatric complications to oral treatment. Parkinsonism Rel Disord 1997; 3: 103–7

    Article  CAS  Google Scholar 

  165. Ostergaard L, Werdelin L, Odin P, et al. Pen injected apomorphine against off phenomena in late Parkinson’s disease: a double blind, placebo controlled study. J Neurol Neurosurg Psychiatry 1995; 58: 681–7

    Article  PubMed  CAS  Google Scholar 

  166. Sampapio C, Branco MC, Rosa MM. A pharmacokinetic interaction between subcutaneous apomorphine and levodopa/carbidopa (Sinemet). Clin Drug Invest 1995; 9: 363–5

    Article  Google Scholar 

  167. Coudore F, Durif F, Duroux E, et al. Effect of tolcapone on plasma and striatal apomorphine disposition in rats. Neuroreport 1997; 8: 877–80

    Article  PubMed  CAS  Google Scholar 

  168. Piercey MF. Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson’s disease. Clin Neuropharmacol 1998; 21: 141–51

    PubMed  CAS  Google Scholar 

  169. Albani C, Popescu R, Lacher R, et al. Single dose response to pramipexole in patients with Parkinson’s disease [abstract]. Mov Disord 1992;7:P271

    Google Scholar 

  170. Dooley M, Markham A. Pramipexole: a review of its use in the management of early and advanced Parkinson’s disease. Drugs Aging 1998; 12: 495–514

    Article  PubMed  CAS  Google Scholar 

  171. Parkinson Study Group. Safety and efficacy of pramipexole in early Parkinson’s disease: a randomized dose-ranging study. JAMA 1997; 278: 125–30

    Article  Google Scholar 

  172. Parkinson Study Group. Pramipexole vs levodopa as initial treatment for Parkinson’s disease: a randomized controlled trial. JAMA 2000; 284: 1931–8

    Article  Google Scholar 

  173. Pinter MM, Pogarell O, Oertel WH. Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson’s disease: a double blind, placebo controlled, randomised, multicentre study. J Neurol Neurosurg Psychiatry 1999; 66: 436–41

    Article  PubMed  CAS  Google Scholar 

  174. Frucht S, Rogers JD, Greene PE, et al. Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole. Neurology 1999; 52: 1908–10

    Article  PubMed  CAS  Google Scholar 

  175. Eden RJ, Costali B, Domeney AM, et al. Preclinical pharmacology of ropinirole (SK & F 101468-A) a novel dopamine D2 agonist. Pharmacol Biochem Behav 1991; 38: 147–54

    Article  PubMed  CAS  Google Scholar 

  176. Matheson AJ, Spencer CM. Ropinirole: a review of its use in the management of Parkinson’s disease. Drugs 2000; 60: 115–137

    Article  PubMed  CAS  Google Scholar 

  177. Adler CH, Sethi KD, Hauser RA, et al. Ropinirole for the treatment of early Parkinson’s disease. The Ropinirole Study Group. Neurology 1997; 49: 393–9

    Article  PubMed  CAS  Google Scholar 

  178. Korczyn AD, Brunt ER, Larsen JP, et al. A 3-year randomized trial of ropinirole and bromocriptine in early Parkinson’s disease. The 053 Study Group. Neurology 1999; 53: 364–70

    Article  PubMed  CAS  Google Scholar 

  179. Fariello RG. Pharmacodynamic and pharmacokinetic features of cabergoline: rationale for use in Parkinson’s disease. Drugs 1998; 55 Suppl. 1: 10–6

    Article  PubMed  CAS  Google Scholar 

  180. Marsden CD. Clinical experience with cabergoline in patients with advanced Parkinson’s disease treated with levodopa. Drugs 1998; 55 Suppl. 1: 17–22

    Article  PubMed  CAS  Google Scholar 

  181. Del Dotto P, Colzi A, Musatti E, et al. Clinical and pharmacokinetic evaluation of L-dopa and cabergoline cotreatment in Parkinson’s disease. Clin Neuropharmacol 1997; 20: 455–65

    Article  PubMed  Google Scholar 

  182. Jenner P, Smith L, Jackson M, et al. Piribedil induces low levels of dyskinesia in MPTP-treated common marmosets [abstract]. Neurology 2000; 45 Suppl. 3: A53

    Google Scholar 

  183. Jenner P, Taylor AR, Campbell DB. Preliminary investigation of the metabolism of piribedil (ET 495); a new central dopaminergic agonist and potential anti-parkinson agent. J Pharm Pharmacol 1973; 25: 749–50

    Article  PubMed  CAS  Google Scholar 

  184. Mentenopoulos G, Katsarou Z, Bostantjopoulou S, et al. Piribedil therapy in Parkinson’s disease: use of the drug in the retard form. Clin Neuropharmacol 1989; 12: 23–8

    Article  PubMed  CAS  Google Scholar 

  185. Rondot P, Ziegler M. Activity and acceptability of piribedil in Parkinson’s disease: a multicentre study. J Neurol 1992; 239 Suppl. 1: S28–34

    Article  PubMed  Google Scholar 

  186. Dewey SL, Volkow ND, Logan J, et al. Age-related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET). J Neurosci Res 1990; 27: 569–75

    Article  PubMed  CAS  Google Scholar 

  187. Krueger BK. Kinetics and block of dopamine uptake in synaptosomes from rat caudate nucleus. J Neurochem 1990; 55: 260–7

    Article  PubMed  CAS  Google Scholar 

  188. McDonough Jr JH Shih TM. A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs. Pharmacol Biochem Behav 1995; 51: 249–53

    Article  PubMed  CAS  Google Scholar 

  189. Kornhuber J, Parsons CG, Hartmann S, et al. Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies. J Neural Transm Gen Sect 1995; 102: 237–46

    Article  PubMed  CAS  Google Scholar 

  190. He H, McKay G, Midha KK. Development of a sensitive and specific radioimmunoassay for benztropine. J Pharm Sci 1993; 82: 1027–32

    Article  PubMed  CAS  Google Scholar 

  191. Hollmann M, Brode E, Greger G, et al. Biperiden effects and plasma levels in volunteers. Eur J Clin Pharmacol 1984; 27: 619–21

    Article  PubMed  CAS  Google Scholar 

  192. Grimaldi R, Perucca E, Ruberto G, et al. Pharmacokinetic and pharmacodynamic studies following the intravenous and oral administration of the antiparkinsonian drug biperiden to normal subjects. Eur J Clin Pharmacol 1986; 29: 735–7

    Article  PubMed  CAS  Google Scholar 

  193. Rutigliano G, Labout JJ. The bioavailability of orphenadrine hydrochloride after intramuscular and oral administration. J Int Med Res 1982; 10: 447–50

    PubMed  CAS  Google Scholar 

  194. Whiteman PD, Fowle AS, Hamilton MJ, et al. Pharmacokinetics and pharmacodynamics of procyclidine in man. Eur J Clin Pharmacol 1985; 28: 73–8

    Article  PubMed  CAS  Google Scholar 

  195. Burke RE, Fahn S. Pharmacokinetics of trihexyphenidyl after short-term and long-term administration to dystonic patients. Ann Neurol 1985; 18: 35–40

    Article  PubMed  CAS  Google Scholar 

  196. He H, McKay G, Wirshing B, et al. Development and application of a specific and sensitive radioimmunoassay for trihexyphenidyl to a pharmacokinetic study in humans. J Pharm Sci 1995; 84: 561–7

    Article  PubMed  CAS  Google Scholar 

  197. Keränen T, Gordin A, Karlsson M, et al. Inhibition of soluble catechol-O-methyltransferase and single-dose pharmacokinetics after oral and intravenous administration of entacapone. Eur J Clin Pharmacol 1994; 46: 151–7

    Article  PubMed  Google Scholar 

  198. Myllylä VV, Sotaniemi KA, Illi A, et al. Effect of entacapone, a COMT inhibitor, on the pharmacokinetics of levodopa and on cardiovascular responses in patients with Parkinson’s disease. Eur J Clin Pharmacol 1993; 45: 419–23

    Article  PubMed  Google Scholar 

  199. Ruottinen HM, Rinne UK. A double-blind pharmacokinetic and clinical dose-response study of entacapone as an adjuvant to levodopa therapy in advanced Parkinson’s disease. Clin Neuropharmacol 1996; 19: 283–96

    Article  PubMed  CAS  Google Scholar 

  200. Jorga K, Fotteler B, Banken L, et al. Population pharmacokinetics of tolcapone in parkinsonian patients in dose finding studies. Br J Clin Pharmacol 2000; 49: 39–48

    Article  PubMed  CAS  Google Scholar 

  201. Dingemanse J, Jorga K, Zürcher G, et al. Multiple-dose clinical pharmacology of the catechol-O-methyl-transferase inhibitor tolcapone in elderly subjects. Eur J Clin Pharmacol 1996; 50: 47–55

    Article  PubMed  CAS  Google Scholar 

  202. Mahmood I. Clinical pharmacokinetics and pharmacodynamics of selegiline: an update. Clin Pharmacokinet 1997; 33: 91–102

    Article  PubMed  CAS  Google Scholar 

  203. Owen JA, Sribney M, Lawson JS, et al. Capillary gas chromatography of trihexyphenidyl, procyclidine and cycrimine in biological fluids. J Chromatogr 1989; 494: 135–42

    Article  PubMed  CAS  Google Scholar 

  204. Capka V, Xu Y, Chen YH. Stereoselective determination of trihexyphenidyl in human serum by LC-ESI-MS. J Pharm Biomed Anal 1999; 21: 507–17

    Article  PubMed  CAS  Google Scholar 

  205. Nation RL, Triggs EJ, Vine J. Metabolism and urinary excretion of benzhexol in humans. Xenobiotica 1978; 8: 165–9

    Article  PubMed  CAS  Google Scholar 

  206. Doshay LJ, Constable K. Five year follow-up of treatment with trihexyphenidyl (Artane®). JAMA 1954; 154: 1334–6

    Article  CAS  Google Scholar 

  207. Takahashi S, Tohgi H, Yonezawa H, et al. The effect of trihexyphenidyl, an anticholinergic agent, on regional cerebral blood flow and oxygen metabolism in patients with Parkinson’s disease. J Neurol Sci 1999; 167: 56–61

    Article  PubMed  CAS  Google Scholar 

  208. Guthrie SK, Manzey L, Scott D, et al. Comparison of central and peripheral pharmacologic effects of biperiden and trihexyphenidyl in human volunteers. J Clin Psychopharmacol 2000; 20: 77–83

    Article  PubMed  CAS  Google Scholar 

  209. Itoh K, Ikarashi Y, Way EL, et al. Intrastriatal dialysis evidence for a direct inhibitory effect of benztropine on dopamine reuptake. Neurosci Lett 1991; 125: 22–4

    Article  PubMed  CAS  Google Scholar 

  210. Selinger K, Lebel G, Hill HM, et al. High-performance liquid Chromatographic method for the analysis of benztropine in human plasma. J Chromatogr 1989; 491: 248–52

    Article  PubMed  CAS  Google Scholar 

  211. He H, McKay G, Midha KK. Phase I and II metabolites of benztropine in rat urine and bile. Xenobiotica 1995; 25: 857–72

    Article  PubMed  CAS  Google Scholar 

  212. Sureda FX, Gabriel C, Pallas M, et al. In vitro and in vivo protective effect of orphenadrine on glutamate neurotoxicity. Neuropharmacology 1999; 38: 671–7

    Article  PubMed  CAS  Google Scholar 

  213. Contin M, Riva R, Albani F, et al. Simple and rapid GLC method for the determination of orphenadrine in human plasma. Biomed Chromatogr 1987; 2: 193–4

    Article  PubMed  CAS  Google Scholar 

  214. Maurer H, Pfleger K. Screening procedure for the detection of alkanolamine antihistamines and their metabolites in urine using computerized gas chromatography-mass spectrometry. J Chromatogr 1988; 428: 43–60

    Article  PubMed  CAS  Google Scholar 

  215. Hattori H, Yamamoto S, Iwata M, et al. Determination of diphenylmethane antihistaminic drugs and their analogues in body fluids by gas chromatography with surface ionization detection. J Chromatogr 1992; 581: 213–8

    Article  PubMed  CAS  Google Scholar 

  216. Guo Z, Raeissi S, White RB, et al. Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos 1997; 25: 390–3

    PubMed  Google Scholar 

  217. Ellison T. Metabolic studies of 3H-orphenadrine citrate in the rat, dog and rhesus monkey. Arch Int Pharmacodyn Ther 1972; 195: 213–30

    PubMed  CAS  Google Scholar 

  218. Dean K, Land D, Bye A. Analysis of procyclidine in human plasma and urine by gas-liquid chromatography. J Chromatogr 1980; 221: 408–13

    Article  PubMed  CAS  Google Scholar 

  219. Holeman JA, Danielson ND. Microbore liquid chromatography of tertiary amine anticholinergic Pharmaceuticals with tris(2,2’-bipyridine)ruthenium(III) chemiluminescence detection. J Chromatogr Sci 1995; 33: 297–302

    PubMed  CAS  Google Scholar 

  220. Rogiers V, Paeme G, Sonck W, et al. Metabolism of procyclidine in isolated rat hepatocytes. Xenobiotica 1987; 17: 849–57

    Article  PubMed  CAS  Google Scholar 

  221. Le Bris T, Brode E. Capillary gas Chromatographic determination of biperiden in human plasma. Arzneimittelforschung 1985; 35: 149–51

    PubMed  Google Scholar 

  222. Stell L, Fleckenstein P, Riemann D, et al. A simple but highly sensitive radioreceptor assay for the determination of scopolamine and biperiden in human plasma. Res Commun Chem Pathol Pharmacol 1989; 64: 59–68

    Google Scholar 

  223. Hollmann M, Muller-Peltzer H, Greger G, et al. Pharmacokinetic-dynamic study on different oral biperiden formulations in volunteers. Pharmacopsychiatry 1987; 20: 72–7

    Article  PubMed  CAS  Google Scholar 

  224. Sudo Y, Suhara T, Suzuki K, et al. Muscarinic receptor occupancy by biperiden in living human brain. Life Sci 1999; 64: 99–104

    Article  Google Scholar 

  225. Villares JC, Carlini EA. Sebum secretion in idiopathic Parkinson’s disease: effect of anticholinergic and dopaminergic drugs. Acta Neurol Scand 1989; 80: 57–63

    Article  PubMed  CAS  Google Scholar 

  226. Schrag A, Schelosky L, Scholz U, et al. Reduction of Parkinsonian signs in patients with Parkinson’s disease by dopaminergic versus anticholinergic single-dose challenges. Mov Disord 1999; 14: 252–5

    Article  PubMed  CAS  Google Scholar 

  227. Roberts J, Waller DG, von Renwick AG, et al. The effects of co-administration of benzhexol on the peripheral pharmacokinetics of oral levodopa in young volunteers. Br J Clin Pharmacol 1996; 41: 331–7

    Article  PubMed  CAS  Google Scholar 

  228. Contin M, Riva R, Martinelli P, et al. Combined levodopa-anticholinergic therapy in the treatment of Parkinson’s disease: effect on levodopa bioavailability. Clin Neuropharmacol 1991; 14: 148–55

    Article  PubMed  CAS  Google Scholar 

  229. Schwab RS, England AC, Poskanzer DC, et al. Amantadme in the treatment of Parkinson’s disease. JAMA 1969; 208: 1168–70

    Article  PubMed  CAS  Google Scholar 

  230. Kulisevsky J, Tolosa E. Amantadme in Parkinson’s disease. In: Koller WC, Paulson GW, editors. Therapy of Parkinson’s disease. New York: Marcel-Dekker, 1990: 143–60

    Google Scholar 

  231. Stoof JC, Booij J, Drukarch B, et al. The anti-parkinsonian drug amantadme inhibits the N-methyl-D-aspartic acid-evoked release of acetylcholine from rat neostriatum in a non-competitive way. Eur J Pharmacol 1992; 213: 439–43

    Article  PubMed  CAS  Google Scholar 

  232. Deep P, Dagher A, Sadikot A, et al. Stimulation of dopa decarboxylase activity in striatum of healthy human brain secondary to NMDA receptor antagonism with a low dose of amantadme. Synapse 1999; 34: 313–8

    Article  PubMed  CAS  Google Scholar 

  233. Zhou FX, Krull IS, Feibush B. Direct determination of adamantanamine in plasma and urine with automated solid phase derivatization. J Chromatogr 1993; 619: 93–101

    Article  PubMed  CAS  Google Scholar 

  234. Shannon KM, Goetz CG, Carroll VS, et al. Amantadme and motor fluctuations in chronic Parkinson’s disease. Clin Neuropharmacol 1987; 10: 522–6

    Article  PubMed  CAS  Google Scholar 

  235. Parkes JD, Baxter RC, Curzon G, et al. Treatment of Parkinson’s disease with amantadme and levodopa: a one-year study. Lancet 1971; I: 1083–6

    Article  Google Scholar 

  236. Greulich W, Fenger E. Amantadme in Parkinson’s disease: pro and contra. J Neural Transm Suppl. 1995; 46: 415–21

    PubMed  CAS  Google Scholar 

  237. Dallos V, Heathfield K, Stone P, et al. The comparative value of amantadme and levodopa. Postgrad Med J 1972; 48: 354–8

    Article  PubMed  CAS  Google Scholar 

  238. Mawdsley C, Williams IR, Pullar IA, et al. Treatment of Parkinsonism with amantadme and levodopa. Clin Pharmacol Ther 1972; 13: 575–83

    PubMed  CAS  Google Scholar 

  239. Luginger E, Wenning GK, Bosch S, et al. Beneficiai effects of amantadme on L-dopa-induced dyskinesias in Parkinson’s disease. Mov Disord 2000; 15: 873–8

    Article  PubMed  CAS  Google Scholar 

  240. Verhagen Metman L, Del Dotto P, LePoole K, et al. Amantadme for levodopa-induced dyskinesias: a 1-year follow-up study. Arch Neurol 1999; 56: 1383–6

    Article  Google Scholar 

  241. Shulman LM, Minagar A, Sharma K, et al. Amantadine-induced peripheral neuropathy. Neurology 1999; 53: 1862–5

    Article  PubMed  CAS  Google Scholar 

  242. Nissinen E, Lindén IB, Schultz E, et al. Biochemical and pharmacological properties of a peripherally acting catechol-O-methyltransferase inhibitor entacapone. Naunyn Schmiedebergs Arch Pharmacol 1992; 346: 262–6

    Article  PubMed  CAS  Google Scholar 

  243. Storch A, Blessing H, Bareiss M, et al. Catechol-O-methyltransferase inhibition attenuates levodopa toxicity in mesencephalic dopamine neurons. Mol Pharmacol 2000; 57: 589–94

    PubMed  CAS  Google Scholar 

  244. Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson’s disease patients. Ann Neurol 1997; 42: 747–55

    Article  Google Scholar 

  245. Rinne UK, Larsen JP, Siden A, et al. Entacapone enhances the response to levodopa in parkinsonian patients with motor fluctuations. Nomecomt Study Group. Neurology 1998; 51: 1309–14

    Article  PubMed  CAS  Google Scholar 

  246. Baas H, Beiske AG, Ghika J, et al. Catechol-O-methyltransferase inhibition with tolcapone reduces the ’wearing off phenomenon and levodopa requirements in fluctuating parkinsonian patients. J Neurol Neurosurg Psychiatry 1997; 63: 421–8

    Article  PubMed  CAS  Google Scholar 

  247. Rajput AH, Martin W, Saint-Hilaire MH, et al. Tolcapone improves motor function in parkinsonian patients with the ‘wearing-off’ phenomenon: a double-blind, placebo-controlled, multicenter trial. Neurology 1997; 49: 1066–71

    Article  PubMed  CAS  Google Scholar 

  248. Karlsson M, Wikberg T. Liquid Chromatographic determination of a new catechol-O-methyltransferase inhibitor, entacapone, and its Z-isomer in human plasma and urine. J Pharm Biomed Anal 1992; 10: 593–600

    Article  PubMed  CAS  Google Scholar 

  249. Timm U, Erdin R. Determination of the catechol-O-methyltransferase inhibitor Ro 40-7592 in human plasma by high-performance liquid chromatography with coulometric detection. J Chromatogr 1992; 593: 63–8

    Article  PubMed  CAS  Google Scholar 

  250. Lehtonen P, Lehtinen S, Malkki-Laine L, et al. Micellar electrokinetic capillary chromatography method for direct determination of glucuronides of entacapone and its (Z)-isomer in human urine. J Chromatogr A 1999; 836: 173–88

    Article  PubMed  CAS  Google Scholar 

  251. De Santi C, Giulianotti PC, Pietrabissa A, et al. Catechol-O-methyltransferase: variation in enzyme activity and inhibition by entacapone and tolcapone. Eur J Clin Pharmacol 1998; 54: 215–9

    Article  PubMed  Google Scholar 

  252. Sawle GV, Burn DJ, Morrish PK, et al. The effect of entacapone (OR-611) on brain [18F]-6-L-fluorodopa metabolism: implications for levodopa therapy of Parkinson’s disease. Neurology 1994; 44: 1292–7

    Article  PubMed  CAS  Google Scholar 

  253. Wikberg T, Vuorela A, Ottoila P, et al. Identification of major metabolites of the catechol-O-methyltransferase inhibitor entacapone in rats and humans. Drug Metab Dispos 1993; 21: 81–92

    PubMed  CAS  Google Scholar 

  254. Keränen T, Gordin A, Harjola VP, et al. The effect of catechol-O-methyl transferase inhibition by entacapone on the pharmacokinetics and metabolism of levodopa in healthy volunteers. Clin Neuropharmacol 1993; 16: 145–56

    Article  PubMed  Google Scholar 

  255. Nutt JG, Woodward WR, Beckner RM, et al. Effectof peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Neurology 1994; 44: 913–9

    Article  PubMed  CAS  Google Scholar 

  256. Piccini P, Brooks D, Korpela K, et al. Entacapone enhances the pharmacokinetic and clinical response of levodopa when administered with Sinemet depot [abstract]. Eur J Neurol 1998; 5 Suppl. 3: S 165

    Google Scholar 

  257. Trocóniz IF, Naukkarinen TH, Ruottinen HM, et al. Population pharmacodynamic modeling of levodopa in patients with Parkinson’s disease receiving entacapone. Clin Pharmacol Ther 1998; 64: 106–16

    Article  PubMed  Google Scholar 

  258. Günther I, Psylla M, Reddy GN, et al. Positron emission tomography in drug evaluation: influence of three different catechol-O-methyltransferase inhibitors on metabolism of [NCA] 6-[18F]fluoro-L-dopa in rhesus monkey. Nucl Med Biol 1995; 22: 921–7

    Article  PubMed  Google Scholar 

  259. Russ H, Muller T, Woitalla D, et al. Detection of tolcapone in the cerebrospinal fluid of parkinsonian subjects. Naunyn Schmiedebergs Arch Pharmacol 1999; 360: 719–20

    Article  PubMed  CAS  Google Scholar 

  260. Jorga KM, Kroodsma JM, Fotteler B, et al. Effect of liver impairment on the pharmacokinetics of tolcapone and its metabolites. Clin Pharmacol Ther 1998; 63: 646–54

    Article  PubMed  CAS  Google Scholar 

  261. Jorga K, Fotteler B, Sedek G, et al. The effect of tolcapone on levodopa pharmacokinetics is independent of levodopa/carbidopa formulation. J Neurol 1998; 245: 223–30

    Article  PubMed  CAS  Google Scholar 

  262. Tohgi H, Abe T, Yamazaki K, et al. Effects of the catechol-O-methyltransferase inhibitor tolcapone in Parkinson’s disease: correlations between concentrations of dopaminergic substances in the plasma and cerebrospinal fluid and clinical improvement. Neurosci Lett 1995; 192: 165–8

    Article  PubMed  CAS  Google Scholar 

  263. Dingemanse J, Jorga K, Zürcher G, et al. Pharmacokinetic-pharmacodynamic interaction between the COMT inhibitor tolcapone and single-dose levodopa. Br J Clin Pharmacol 1995; 40: 253–62

    Article  PubMed  CAS  Google Scholar 

  264. Waters CH, Kurth M, Bailey P, et al. Tolcapone in stable Parkinson’s disease: efficacy and safety of long-term treatment. The Tolcapone Stable Study Group. Neurology 1997; 49: 665–71

    Article  PubMed  CAS  Google Scholar 

  265. Adler CH, Singer C, O’Brien C, et al. Randomized, placebocontrolled study of tolcapone in patients with fluctuating Parkinson disease treated with levodopa-carbidopa. Tolcapone Fluctuator Study Group III. Arch Neurol 1998; 55: 1089–95

    Article  PubMed  CAS  Google Scholar 

  266. Kurth MC, Adler CH, Hilaire MS, et al. Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson’s disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Tolcapone Fluctuator Study Group I. Neurology 1997; 48: 81–7

    Article  PubMed  CAS  Google Scholar 

  267. Dupont E, Burgunder JM, Findley LJ, et al. Tolcapone added to levodopa in stable parkinsonian patients: a double-blind placebo-controlled study. Tolcapone in Parkinson’s Disease Study Group II (TIPS II). Mov Disord 1997; 12: 928–34

    Article  PubMed  CAS  Google Scholar 

  268. Tolcapone Study Group. Efficacy and tolerability of tolcapone compared with bromocriptine in levodopa-treated parkinsonian patients. Mov Disord 1999; 14: 38–44

    Article  Google Scholar 

  269. Hauser RA, Molho E, Shale H, et al. A pilot evaluation of the tolerability, safety, and efficacy of tolcapone alone and in combination with oral selegiline in untreated Parkinson’s disease patients. Tolcapone De Novo Study Group. Mov Disord 1998; 13: 643–7

    Article  PubMed  CAS  Google Scholar 

  270. Assai F, Spahr L, Hadengue A, et al. Tolcapone and fulminant hepatitis [letter]. Lancet 1998; 352: 958

    Google Scholar 

  271. Ellison RH. Dear health professional letter regarding appropriate use of Tasmar. Nutley, (NJ): Roche Laboratories Inc, November 16, 1998

    Google Scholar 

  272. Olanow CW, Tasmar Advisory Panel. Tolcapone and hepatotoxic effects. Arch Neurol 2000; 57: 263–7

    Article  PubMed  CAS  Google Scholar 

  273. Olanow CW. Hepatic safety of the COMT inhibitor entacapone [abstract]. Neurology 2000; 54 Suppl. 3: A279

    Google Scholar 

  274. Lyytinen J, Kaakkola S, Teräväinen H, et al. Comparison between the effects of L-dopa + entacapone and L-dopa + placebo on exercise capacity, haemodynamics and autonomic function in patients with Parkinson’s disease [abstract]. Mov Disord 1997; 12 Suppl. 1: 103

    Article  Google Scholar 

  275. Sundberg S, Scheinin M, Ojala-Karlsson P, et al. The effects of the COMT inhibitor entacapone on haemodynamics and peripheral catecholamine metabolism during exercise. Br J Clin Pharmacol 1993; 36: 451–6

    Article  PubMed  CAS  Google Scholar 

  276. Deleu D. COMT inhibition in Parkinson’s disease: rationale and clinical relevance. Acta Neurol Belg 2000; 100: 5–7

    PubMed  CAS  Google Scholar 

  277. Deleu D. Endogenous dopamine-derived neurotoxins and Parkinson’s disease. Acta Neurol Belg 1998; 98: 319–21

    PubMed  CAS  Google Scholar 

  278. Jorga KM, Nicholl DJ. COMT inhibition with tolcapone does not affect carbidopa pharmacokinetics in parkinsonian patients in levodopa/carbidopa (Sinemet). Br J Clin Pharmacol 1999; 48: 449–52

    Article  PubMed  CAS  Google Scholar 

  279. Jorga KM, Larsen JP, Beiske A, et al. The effect of tolcapone on the pharmacokinetics of benserazide. Eur J Neurol 1999; 6: 211–9

    Article  PubMed  CAS  Google Scholar 

  280. Olanow CW, Mytilineou C, Tatton W. Current status of selegiline as a neuroprotective agent in Parkinson’s disease. Mov Disord 1998; 13 Suppl. 1: 55–8

    PubMed  Google Scholar 

  281. Dingemanse J, Wood N, Jorga K, et al. Pharmacokinetics and pharmacodynamics of single and multiple doses of the MAO-B inhibitor lazabemide in healthy subjects. Br J Clin Pharmacol 1997; 43: 41–7

    Article  PubMed  CAS  Google Scholar 

  282. Tatton WG, Greenwood CE. Rescue of dying neurons: a new action for deprenyl in MPTP parkinsonism. J Neurosci Res 1991; 30: 666–72

    Article  PubMed  CAS  Google Scholar 

  283. La Croix R, Pianezzola E, Strolin Benedetti M. Sensitive high-performance liquid Chromatographic method for the determination of the three main metabolites of selegiline (L-deprenyl) in human plasma. J Chromatogr B Biomed Appl 1994; 656: 251–8

    Article  PubMed  Google Scholar 

  284. Salonen JS. Determination of the amine metabolites of selegiline in biological fluids by capillary gas chromatography. J Chromatogr 1990; 527: 163–8

    Article  PubMed  CAS  Google Scholar 

  285. Reimer ML, Mamer OA, Zavitsanos AP, et al. Determination of amphetamine, methamphetamine and desmethyldeprenyl in human plasma by gas Chromatography/negative ion chemical ionization mass spectrometry. Biol Mass Spectrom 1993; 22: 235–42

    Article  PubMed  CAS  Google Scholar 

  286. Laine K, Anttila M, Huupponen R, et al. Multiple-dose pharmacokinetics of selegiline and desmethylselegiline suggest saturable tissue binding. Clin Neuropharmacol 2000; 23: 22–7

    Article  PubMed  CAS  Google Scholar 

  287. Fowler JS, Volkow ND, Logan J, et al. Slow recovery of human brain MAO B after L-deprenyl (selegiline) withdrawal. Synapse 1994; 18: 86–93

    Article  PubMed  CAS  Google Scholar 

  288. The Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1989; 32: 1364–71

    Google Scholar 

  289. Brannan T, Yahr MD. Comparative study of selegiline plus L-dopa-carbidopa versus L-dopa-carbidopa alone in the treatment of Parkinson’s disease. Ann Neurol 1995; 37: 95–8

    Article  PubMed  CAS  Google Scholar 

  290. Lees AJ. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson’s disease. Parkinson’s Disease Research Group of the United Kingdom. BMJ 1995; 311: 1602–7

    Article  PubMed  CAS  Google Scholar 

  291. Olanow CW, Hauser RA, Gauger L, et al. The effect of deprenyl and levodopa on the progression of Parkinson’s disease. Ann Neurol 1995; 38: 771–7

    Article  PubMed  CAS  Google Scholar 

  292. The Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1993; 328: 176–83

    Article  Google Scholar 

  293. Palhagen S, Heinonen EH, Hagglund J, et al. Selegiline delays the onset of disability in de novo parkinsonian patients. Swedish Parkinson Study Group. Neurology 1998; 51: 520–5

    Article  PubMed  CAS  Google Scholar 

  294. Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP subjects not requiring levodopa. Ann Neurol 1996; 39: 29–36

    Article  Google Scholar 

  295. Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP patients requiring levodopa. Ann Neurol 1996; 39: 37–45

    Article  Google Scholar 

  296. Ward CD. Does selegiline delay the progression of Parkinson’s disease: a critical re-evaluation of the DATATOP study. J Neurol Neurosurg Psychiatry 1994; 57: 217–20

    Article  PubMed  CAS  Google Scholar 

  297. Rinne JO. Nigral degeneration in Parkinson’s disease in relation to clinical features. Acta Neurol Scand Suppl. 1991; 316: 87–90

    Article  Google Scholar 

  298. Olanow CW, Myllylä VV, Sotaniemi KA, et al. Effect of selegiline on mortality in patients with Parkinson’s disease: a metaanalysis. Neurology 1998; 51: 825–30

    Article  PubMed  CAS  Google Scholar 

  299. Donnan PT, Steinke DT, Stubbings C, et al. Selegiline and mortality in subjects with Parkinson’s disease: a longitudinal community study. Neurology 2000; 55: 1785–9

    Article  PubMed  CAS  Google Scholar 

  300. Chrisp P, Mammen GJ, Sorkin EM. Selegiline: a review of its pharmacology, symptomatic benefits and protective potential in Parkinson’s disease. Drugs Aging 1991; 1: 228–48

    Article  PubMed  CAS  Google Scholar 

  301. Pal S, Bhattacharya KF, Agapito C, et al. A study of excessive daytime sleepiness and its clinical significance in three groups of Parkinson’s disease patients taking pramipexole, cabergoline and levodopa mono and combination therapy. J Neural Transm 2001; 108: 71–7

    Article  PubMed  CAS  Google Scholar 

  302. Ferreira JJ, Galitzky M, Montastruc JL, et al. Sleep attacks and Parkinson’s disease treatment. Lancet 2000; 355: 1333–4

    Article  PubMed  CAS  Google Scholar 

  303. Etminan M, Samii A, Takkouche B, et al. Increased risk of somnolence with the new dopamine agonists in patients with Parkinson’s disease: a meta-analysis of randomised controlled trials. Drug Saf 2001; 24: 863–8

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

There are no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. College of Medicine, Sultan Qaboos University, PO Box 35, Al Khod, PC-123, Sultanate of Oman

    Dirk Deleu & Margaret G. Northway

  2. Pharmacy Department, Drug Information Services, Sultan Qaboos University Hospital, Al Khod, Oman

    Yolande Hanssens

Authors
  1. Dirk Deleu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Margaret G. Northway
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yolande Hanssens
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dirk Deleu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Deleu, D., Northway, M.G. & Hanssens, Y. Clinical Pharmacokinetic and Pharmacodynamic Properties of Drugs Used in the Treatment of Parkinson’s Disease. Clin Pharmacokinet 41, 261–309 (2002). https://doi.org/10.2165/00003088-200241040-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-200241040-00003

Keywords

Search

Navigation