Drugs & Aging

, Volume 13, Issue 5, pp 381–389 | Cite as

Clinical Pharmacology of Dopamine Agonists in Parkinson’s Disease

  • Klaus W. LangeEmail author
Review Article Clinical Pharmacology


Oral levodopa is the most effective symptomatic treatment for Parkinson’s disease. Dopamine agonists are useful adjuvants to levodopa in the pharmacotherapy of parkinsonian patients. Monotherapy with dopamine agonists in early Parkinson’s disease has been advocated in order to delay the occurrence of complications associated with long term administration of levodopa. The use of dopamine agonists alone provides an adequate antiparkinsonian effect in only a minority of patients. In early stages of Parkinson’s disease, dopamine agonists can produce a clinical response comparable with levodopa but, thereafter, their efficacy wanes. Early initiation of combination therapy with levodopa and dopamine agonists appears to reduce the severity and delay the appearance of the complications associated with long term administration of levodopa.

Currently, dopamine agonists are most commonly used in combination with levodopa in patients in advanced stages of the disease who experience fluctuations of their motor symptoms. Despite their different pharmacodynamic and pharmacokinetic profiles, the ergot derivatives bromocriptine, lisuride and pergolide appear to be very similar in terms of their clinical efficacy. Continuous dopaminergic stimulation by parenteral infusion of water-soluble dopamine agonists such as apomorphine and lisuride can overcome motor fluctuations in advanced Parkinson’s disease. Other dopamine agonists such as cabergoline, pramipexole and ropinirole are currently being studied. Further studies with these compounds will be required to determine their efficacy and adverse effects in comparison with the currently available orally active ergot agonists. It has been suggested that oxidative stress resulting from dopamine metabolism may be reduced by the administration of dopamine agonists. These drugs may therefore slow the rate of progression of Parkinson’s disease. At present, however, there is no convincing clinical data to support a neuroprotective effect of dopamine agonists.


Levodopa Bromocriptine Dopamine Agonist Apomorphine Pramipexole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Birkmayer W, Riederer P. Parkinson’s disease. New York: Springer, 1983Google Scholar
  2. 2.
    Hughes AJ, Daniel SE, Kilford L, et al. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992; 55: 181–4PubMedCrossRefGoogle Scholar
  3. 3.
    Marsden CD, Parkes JD. ‘On-off’ effects in patients with Parkinson’s disease on chronic levodopa therapy. Lancet 1976; I: 292–6CrossRefGoogle Scholar
  4. 4.
    Lesser RP, Fahn S, Snider SR, et al. Analysis of the clinical problems in parkinsonism and the complications of long-term levodopa therapy. Neurology 1979; 29: 1253–60PubMedCrossRefGoogle Scholar
  5. 5.
    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: 151–201PubMedCrossRefGoogle Scholar
  6. 6.
    Calne DB. Treatment of Parkinson’s disease. N Engl J Med 1993; 329: 1021–7PubMedCrossRefGoogle Scholar
  7. 7.
    Kebabian JW, Calne DB. Multiple receptors for dopamine. Nature 1979; 277: 93–6PubMedCrossRefGoogle Scholar
  8. 8.
    Strange PG. Dopamine receptors in the basal ganglia: relevance to Parkinson’s disease. Mov Disord 1994; 8: 263–70CrossRefGoogle Scholar
  9. 9.
    Schwartz R, Fuxe K, Agnati LF. Effect of bromocriptine on 3H spiroperidol binding sites in rat striatum: evidence for actions of dopamine receptors not linked to adenylate cyclase. Life Sci 1978; 23: 465–70CrossRefGoogle Scholar
  10. 10.
    Markstein R. Neurochemical effects of some ergot derivatives: a basis for their antiparkinsonian actions. J Neural Transm 1981; 51: 39–59PubMedCrossRefGoogle Scholar
  11. 11.
    Goetz CG. Dopaminergic agonists in the treatment of Parkinson’s disease. Neurology 1990; 40Suppl. 1: 50–4PubMedGoogle Scholar
  12. 12.
    Robertson GS, Robertson HA. Synergistic effects of D1 and D2 dopamine agonists on turning behaviour in rats. Brain Res 1986; 384: 387–90PubMedCrossRefGoogle Scholar
  13. 13.
    Löschmann P-A, Smith LA, Lange KW, et al. Motor activity following the administration of selective D-1 and D-2 dopaminergic drugs to MPTP-treated common marmosets. Psychopharmacology 1992; 109: 49–56PubMedCrossRefGoogle Scholar
  14. 14.
    Grondin R, Bedard PJ, Britton DR, et al. Potential therapeutic use of the selective dopamine D1 receptor agonist, A-86929: an acute study in parkinsonian levodopa-primed monkeys. Neurology 1997; 49: 421–6PubMedCrossRefGoogle Scholar
  15. 15.
    Montastruc JL, Rascol O, Rascol A. A randomized controlled study of bromocriptine versus levodopa in previously untreated parkinsonian patients: a three-year follow-up. J Neurol Neurosurg Psychiatry 1989; 52: 773–5PubMedCrossRefGoogle Scholar
  16. 16.
    Rinne UK. Lisuride, a dopamine agonist in the treatment of early Parkinson’s disease. Neurology 1989; 39: 336–9PubMedCrossRefGoogle Scholar
  17. 17.
    Horstink MWIM, Zijlmans JCM, Pasman JW, et al. Severity of Parkinson’s disease is a risk factor for peak-dose dyskinesia. J Neurol Neurosurg Psychiatry 1990; 53: 224–6PubMedCrossRefGoogle Scholar
  18. 18.
    Horstink MWIM, Zijlmans JCM, Pasman JW, et al. Which risk factors predict the levodopa response in fluctuating Parkinson’s disease. Ann Neurol 1990; 27: 537–43PubMedCrossRefGoogle Scholar
  19. 19.
    Roos RAC, Vredevoogd CB, Vandervelde EA. Response fluctuations in Parkinson’s disease. Neurology 1990; 40: 1344–6PubMedCrossRefGoogle Scholar
  20. 20.
    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: 21–7PubMedCrossRefGoogle Scholar
  21. 21.
    Jankovic J. Long-term use of dopamine agonists in Parkinson’s disease. Clin Neuropharmacol 1985; 8: 131–40PubMedCrossRefGoogle Scholar
  22. 22.
    Riopelle RJ. Bromocriptine and the clinical spectrum of Parkinson’s disease. Can J Neurol Sci 1987; 14: 455–9PubMedGoogle Scholar
  23. 23.
    Lees AJ, Stern GM. Sustained bromocriptine therapy in previously untreated patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 1981; 44: 1020–3PubMedCrossRefGoogle Scholar
  24. 24.
    Grimes JD, Delgado MR. Bromocriptine: problems with low-dose Je novo therapy in Parkinson’s disease. Clin Neuropharmacol 1985; 8: 73–7PubMedCrossRefGoogle Scholar
  25. 25.
    Rinne UK. Combined bromocriptine-levodopa therapy early in Parkinson’s disease. Neurology 1985; 35: 1196–8PubMedCrossRefGoogle Scholar
  26. 26.
    Quinn N, Illas A, Lhermitte F, et al. Bromocriptine and domperidone in the treatment of Parkinson’s disease. Neurology 1981; 31: 662–7PubMedCrossRefGoogle Scholar
  27. 27.
    Lieberman AN, Goldstein M, Leibowitz M, et al. Long-term treatment with pergolide: decreased efficacy with time. Neurology 1984; 34: 223–6PubMedCrossRefGoogle Scholar
  28. 28.
    Goetz CG, Tanner CM, Glantz RH, et al. Chronic agonist therapy for Parkinson’s disease: a five-year study of bromocriptine and pergolide. Neurology 1985; 35: 749–51PubMedCrossRefGoogle Scholar
  29. 29.
    Goetz CG, Shannon KM, Tanner CM, et al. Agonist substitution in advanced Parkinson’s disease. Neurology 1989; 39: 1121–2PubMedCrossRefGoogle Scholar
  30. 30.
    Factor SA, Sanchez-Ramos JR, Weiner WJ. Parkinson’s disease: an open label trial of pergolide in patients failing bromocriptine therapy. J Neurol Neurosurg Psychiatry 1988: 51: 529–33PubMedCrossRefGoogle Scholar
  31. 31.
    LeWitt PA, Ward CD, Larsen TA, et al. Comparison of pergolide and bromocriptine therapy in parkinsonism. Neurology 1983; 33: 1009–14PubMedCrossRefGoogle Scholar
  32. 32.
    Hardie RJ, Lees AJ, Stern GM. On-off fluctuations in Parkinson’s disease: a clinical and neuropharmacological study. Brain 1984; 107: 487–506PubMedCrossRefGoogle Scholar
  33. 33.
    Sage JI, Trooskin S, Sonsalla PK, et al. Long-term duodenal infusion of levodopa for motor fluctuations in parkinsonism. Ann Neurol 1988; 24: 87–9PubMedCrossRefGoogle Scholar
  34. 34.
    Obeso JA, Luquin MR, Martinez-Lage JM. Lisuride infusion pump: a device for the treatment of motor fluctuations. Lancet 1986; I: 467–70CrossRefGoogle Scholar
  35. 35.
    Stibe CMH, Lees AJ, Stern GM. Subcutaneous infusion of apomorphine and lisuride in the treatment of parkinsonian on-off fluctuations [letter]. Lancet 1987; I: 871CrossRefGoogle Scholar
  36. 36.
    Frankel JP, Lees AJ, Kempster PA, et al. Subcutaneous apomorphine in the treatment of Parkinson’s disease. J Neurol Neurosurg Psychiatry 1990; 53: 96–101PubMedCrossRefGoogle Scholar
  37. 37.
    Coleman RJ, Lange KW, Quinn NP, et al. The antiparkinsonian actions and pharmacokinetics of transdermal (+)-4-propyl-9-hydroxynaphthoxazine (+PHNO): preliminary results. Mov Disord 1990; 4: 129–38CrossRefGoogle Scholar
  38. 38.
    Lange KW, Youdim MBH, Riederer P. Neurotoxicity and neuroprotection in Parkinson’s disease. J Neural Transm 1992; Suppl. 38: 27–44Google Scholar
  39. 39.
    Sofic E, Lange KW, Jellinger K, et al. Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease. Neurosci Lett 1992; 142: 128–30PubMedCrossRefGoogle Scholar
  40. 40.
    Saggu H, Cooksey J, Dexter D, et al. A selective increase in particulate Superoxide dismutase activity in parkinsonian substantia nigra. J Neurochem 1989; 53: 692–7PubMedCrossRefGoogle Scholar
  41. 41.
    Lange KW, Löschmann P-A, Sofic E, et al. The competitive NMDA antagonist CPP protects substantia nigra neurones from MPTP-induced degeneration in primates. Naunyn-Schmiedebergs Arch Pharmacol 1993; 348: 586–92PubMedCrossRefGoogle Scholar
  42. 42.
    Lange KW, Riederer P. Glutamatergic drugs in Parkinson’s disease. Life Sci 1994; 54: 2067–75CrossRefGoogle Scholar
  43. 43.
    Lange KW, Rausch W-D, Gsell W, et al. Neuroprotection by dopamine agonists. J Neural Transm 1994; Suppl. 43: 183–201Google Scholar
  44. 44.
    Lange KW, Kornhuber J, Riederer P. Dopamine/glutamate interactions in Parkinson’s disease. Neurosci Biobehav Rev 1997; 21: 393–400PubMedCrossRefGoogle Scholar
  45. 45.
    Felten DF, Felten SY, Fuller RW, et al. Chronic dietary pergolide preserves nigrostriatal neuronal integrity in aged Fischer-344 rats. Neurobiol Aging 1992; 13: 339–51PubMedCrossRefGoogle Scholar
  46. 46.
    Clow A, Hussain T, Glover V, et al. Pergolide can induce soluble Superoxide dismutase in rat striata. J Neural Transm Gen Sect 1992; 90: 27–31PubMedCrossRefGoogle Scholar
  47. 47.
    Ubeda A, Montesinos C, Paya M, et al. Iron-reducing and free-radical scavenging properties of apomorphine and some related benzylisoquinolines. Free Radic Biol Med 1993; 15: 159–67PubMedCrossRefGoogle Scholar
  48. 48.
    Yoshikawa T, Minamiyama Y, Naito Y, et al. Antioxidant properties of bromocriptine, a dopamine agonist. J Neurochem 1994; 62: 1034–8PubMedCrossRefGoogle Scholar
  49. 49.
    Runge I, Horowski R. Can we differentiate symptomatic and neuroprotective effects in Parkinsonism? The dopamine agonist lisuride delays the need for levodopa therapy to a similar extent as reported for deprenyl. J Neural Transm Park Dis Dem Sect 1991; 4: 273–83Google Scholar
  50. 50.
    Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1989; 321: 1364–7CrossRefGoogle Scholar
  51. 51.
    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: 771–7PubMedCrossRefGoogle Scholar
  52. 52.
    Lichter D, Kurlan R, Miller C, et al. Does pergolide slow the progression of Parkinson’s disease? A 7-year follow-up study [abstract]. Neurology 1988; 38Suppl. 1: 122Google Scholar
  53. 53.
    Zimmerman T, Sage JI. Comparison of combination pergolide and levodopa to levodopa alone after 63 months of treatment. Clin Neuropharmacol 1991; 14: 165–9PubMedCrossRefGoogle Scholar
  54. 54.
    Lieberman AN, Neophytides AV, Leibowitz M, et al. Comparative efficacy of pergolide and bromocriptine in patients with advanced Parkinson’s disease. Adv Neurol 1983; 37: 95–108PubMedGoogle Scholar
  55. 55.
    Mannen T, Mizuno Y, Iwata M, et al. A multi-center, double-blind study on slow-release bromocriptine in the treatment of Parkinson’s disease. Neurology 1991; 41: 1598–602PubMedCrossRefGoogle Scholar
  56. 56.
    Horowski R, Wachtel H. Direct dopaminergic action of lisuride hydrogen maleate, an ergot derivative, in mice. Eur J Pharmacol 1976; 36: 373–83PubMedCrossRefGoogle Scholar
  57. 57.
    Stocchi F, Bramante L, Monge A, et al. Apomorphine and lisuride infusion: a comparative chronic study. Adv Neurol 1993; 60: 653–5PubMedGoogle Scholar
  58. 58.
    Vaamonde J, Luquin MR, Obeso JA. Subcutaneous lisuride infusion in Parkinson’s disease: response to chronic administration in 34 patients. Brain 1991; 114: 601–14PubMedCrossRefGoogle Scholar
  59. 59.
    Neumeyer JL, Samarthji L, Balderassini RJ. Historical highlights of the chemistry, pharmacology and early clinical uses of apomorphine. In: Gesse GL, Corsini GU, editors. Apomorphine and other dopaminomimetics. Vol. 1. Pharmacology. New York: Raven Press, 1981Google Scholar
  60. 60.
    Stibe CM, Kempster PA, Lees AJ, et al. Subcutaneous apomorphine in parkinsonian on-off oscillations. Lancet 1988; I: 403–6CrossRefGoogle Scholar
  61. 61.
    Yahr MD, Clough CC, Bergmann KJ. Cholinergic and dopaminergic mechanisms in Parkinson’s disease after long-term levodopa administration. Lancet 1982; II: 709–10CrossRefGoogle Scholar
  62. 62.
    Gancher ST, Nutt JG, Woodward WR. Apomorphine infusional therapy in Parkinson’s disease: clinical utility and lack of tolerance. Mov Disord 1995; 10: 37–43PubMedCrossRefGoogle Scholar
  63. 63.
    Kapoor R, Turjanski N, Frankel J, et al. Intranasal apomorphine: a new treatment in Parkinson’s disease [letter]. J Neurol Neurosurg Psychiatry 1990; 53: 1015PubMedCrossRefGoogle Scholar
  64. 64.
    Lees AJ, Montastruc JL, Turjanski N, et al. Sublingual apomorphine and Parkinson’s disease [letter]. J Neurol Neurosurg Psychiatry 1989; 52: 1440PubMedCrossRefGoogle Scholar
  65. 65.
    Hughes AJ, Bishop S, Lees AJ, et al. Rectal apomorphine in Parkinson’s disease [letter]. Lancet 1991; 337: 118PubMedCrossRefGoogle Scholar
  66. 66.
    Gancher ST, Nutt JG, Woodward WR. Absorption of apomorphine by various routes in parkinsonism. Mov Disord 1991; 6: 212–6PubMedCrossRefGoogle Scholar
  67. 67.
    Dewey Jr RB, Maraganore DM, Ahlskog JE, et al. Intranasal apomorphine rescue therapy for parkinsonian ‘off’ periods. Clin Neuropharmacol 1996; 19: 193–201PubMedCrossRefGoogle Scholar
  68. 68.
    Van Laar T, Neef C, Danhof M, et al. A new sublingual formulation of apomorphine in the treatment of patients with Parkinson’s disease. Mov Disord 1996; 11: 633–8PubMedCrossRefGoogle Scholar
  69. 69.
    Lera G, Vaamonde J, Muruzabal J, et al. Cabergoline: a long-acting dopamine agonist in Parkinson’s disease. Ann Neurol 1990; 28: 593–4PubMedCrossRefGoogle Scholar
  70. 70.
    Lieberman A, Imke S, Muenter M, et al. Multicenter study of cabergoline, a long-acting dopamine agonist, in Parkinson’s disease patients with fluctuating responses to levodopa/carbidopa. Neurology 1993; 43: 1981–4PubMedCrossRefGoogle Scholar
  71. 71.
    Hutton JT, Morris JL, Brewer MA, et al. Controlled study of the antiparkinsonian activity and tolerability of cabergoline. Neurology 1993; 43: 613–6PubMedCrossRefGoogle Scholar
  72. 72.
    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: 1062–5PubMedCrossRefGoogle Scholar
  73. 73.
    Lera G, Vaamonde J, Rodriguez M, et al. Cabergoline in Parkinson’s disease: long-term follow-up. Neurology 1993; 43: 2587–90PubMedCrossRefGoogle Scholar
  74. 74.
    Hubble JP, Koller WC, Cutler NR, et al. Pramipexole in patients with early Parkinson’s disease. Clin Neuropharmacol 1995; 18: 338–47PubMedCrossRefGoogle Scholar
  75. 75.
    Rascol O, Lees AJ, Senard JM, et al. Ropinirole in the treatment of levodopa-induced motor fluctuations in patients with Parkinson’s disease. Clin Neuropharmacol 1996; 19: 234–45PubMedCrossRefGoogle Scholar
  76. 76.
    Wachtel H, Dorow R. Dual action on central dopamine function of transdihydrolisuride, a 9,10-dihydrogenated analogue of the ergot dopamine agonist lisuride. Life Sci 1983; 32: 421–32PubMedCrossRefGoogle Scholar
  77. 77.
    Lange KW, Löschmann P-A, Wachtel H, et al. Terguride stimulates locomotor activity at 2 months but not 10 months following MPTP treatment of common marmosets. Eur J Pharmacol 1992; 212: 247–52PubMedCrossRefGoogle Scholar
  78. 78.
    Corsini GU, Bonuccelli U, Rainer E, et al. Therapeutic efficacy of a partial dopamine agonist in drug-free parkinsonian patients. J Neural Transm 1985; 64: 105–11PubMedCrossRefGoogle Scholar
  79. 79.
    Bröcke T, Danielczyk W, Simányi M, et al. Terguride: partial dopamine agonist in the treatment of Parkinson’s disease. Adv Neurol 1986; 45: 573–6Google Scholar
  80. 80.
    Critchley P, Parkes D. Transdihydrolisuride in parkinsonism. Clin Neuropharmacol 1987; 10: 57–64PubMedCrossRefGoogle Scholar
  81. 81.
    Baronti F, Mouradian MM, Conant KE, et al. Partial dopamine agonist therapy of levodopa-induced dyskinesias. Neurology 1992; 42: 1241–3PubMedCrossRefGoogle Scholar
  82. 82.
    Ruggieri S, Stocchi F, Baronti F, et al. Antagonist effect of terguride in Parkinson’s disease. Clin Neuropharmacol 1991; 14: 450–6PubMedCrossRefGoogle Scholar
  83. 83.
    Dodel RC, Eggert KM, Singer MS, et al. Costs of drug treatment in Parkinson’s disease. Mov Disord 1998; 13: 249–54PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  1. 1.Department of Neuropsychology and Behavioural NeurobiologyUniversity of RegensburgRegensburgGermany

Personalised recommendations