Skip to main content

Advertisement

SpringerLink
Log in

Continuous dopaminergic stimulation and novel formulations of dopamine agonists

  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

There is now accumulating evidence that the combination of progressive pathology of Parkinson’s disease, the change in drug pharmacodynamics, and the pulsatile manner in which short-acting dopaminergic agents stimulate striatal dopamine receptors are the key contributing factors to the priming of the basal ganglia for induction of motor complications. Long-acting drugs provide a more physiological dopaminergic stimulation. Dopamine agonists have been extensively used as monotherapy and add-on therapy to levodopa to treat Parkinson’s disease in the early stage and with motor complications. Today, the new long-acting formulation offers the advantages of an easy use and a more continuous delivery of drug. In this paper the role of new formulations of dopamine agonists in the treatment of parkinsonian patients at different stages of the disease is reviewed.

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

Similar content being viewed by others

References

  1. Olanow CW, Watts RL, Koller WC (2001) An algorithm (decision tree) for the management of Parkinson’s disease: treatment guidelines. Neurology 56(Suppl 5):S1–S86

    PubMed  CAS  Google Scholar 

  2. Agid Y, Olanow C, Mizuno Y (2002) Levodopa: why the controversy? Lancet 360:575

    Article  PubMed  CAS  Google Scholar 

  3. Miyasaki JM, Martin W, Suchowersky O, Weiner WJ, Lang AE (2002) Practice parameter: initiation of treatment for Parkinson’s disease: an evidence-based review. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 58:11–17

    Google Scholar 

  4. Rascol O, Goetz C, Koller W, Poewe W, Sampaio C (2002) Treatment interventions for Parkinson’s disease: an evidence-based assessment. Lancet 359:1589–1598

    Article  PubMed  Google Scholar 

  5. Korczyn AD, Nussbaum M (2002) Emerging therapies in the pharmacological treatment of Parkinson’s disease. Drugs 62:775–786

    Article  PubMed  CAS  Google Scholar 

  6. Marsden CD, Parkes JD (1977) Success and problems of long-term levodopa therapy in Parkinson’s disease. Lancet 1:345–349

    Article  PubMed  CAS  Google Scholar 

  7. Marsden CD (1994) Parkinson’s disease. J Neurol Neurosurg Psychiatry 57:672–681

    Article  PubMed  CAS  Google Scholar 

  8. Luquin MR, Scipioni O, Vaamonde J, Gershanik O, Obeso JA (1992) Levodopa-induced dyskinesias in Parkinson’s disease: clinical and pharmacological classification. Mov Disord 7:117–124

    Article  PubMed  CAS  Google Scholar 

  9. Marconi R, Lefebvre-Caparros D, Bonnet AM, Vidailhet M, Dubois B, Agid Y (1994) Levodopa-induced dyskinesias in Parkinson’s disease: phenomenology and pathophysiology. Mov Disord 9:2–12

    Article  PubMed  CAS  Google Scholar 

  10. Stocchi F (2009) The hypothesis of the genesis of motor complications and continuous dopaminergic stimulation in the treatment of Parkinson’s disease. Parkinsonism Relat Disord 15(Suppl 1):S9–S15 (Review)

    Google Scholar 

  11. Stacy M, Bowron A, Guttman M, Hauser R, Hughes K, Larsen JP et al (2005) Identification of motor and non motor wearing-off in Parkinson’s disease: Comparison of a patient questionnaire versus a clinician assessment. Mov Disord 20:726–733

    Article  PubMed  Google Scholar 

  12. Olanow CW, Obeso JA, Stocchi F (2006) Continuous dopamine-receptor treatment of Parkinson’s disease: scientific rationale and clinical implications. Lancet Neurol 5:677–687

    Article  PubMed  CAS  Google Scholar 

  13. Grace AA (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41:1–24

    Article  PubMed  CAS  Google Scholar 

  14. Schultz W (1998) Predictive reward signal of dopamine neurons. J Neurophysiol 80:1–27

    PubMed  CAS  Google Scholar 

  15. Abercrombie ED, Bonatz AE, Zigmond MJ (1990) Effects of l-DOPA on extracellular dopamine in striatum of normal and 6-hydroxydopamine-treated rats. Brain Res 525:36–44

    Article  PubMed  CAS  Google Scholar 

  16. Venton BJ, Zhang H, Garris PA, Phillips PE, Sulzer D, Wightman RM (2004) Real-time decoding of dopamine concentrating changes in the caudate-putamen during tonic and phasic firing. J Neurochem 89:1284–1295

    Article  Google Scholar 

  17. Calabresi P (1993) Electrophysiology of dopamine–denervated striatal neurons; implications for Parkinson’s disease. Brain 116:433–452

    Article  PubMed  Google Scholar 

  18. Centonze D, Gubellini P, Picconi B, Calabresi P, Giacomini P, Bernardi G (1999) Unilateral dopamine denervation blocks corticostriatal LTP. J Neurophysiol 82:3575–3579

    PubMed  CAS  Google Scholar 

  19. Picconi B, Centonze D, Hakansson K, Bernardi G, Greengard P, Fisone G et al (2003) Loss of bidirectional striatal synaptic plasticity in l-DOPA-induced dyskinesia. Nat Neurosci 6:501–506

    PubMed  CAS  Google Scholar 

  20. Rodriguez M, Gonzalez J, Sabate M, Obeso J, Pereda E (2003) Firing regulation in dopaminergic cells: effect of the partial degeneration of nigrostriatal system in surviving neurons. Eur J Neurosci 18:53–60

    Article  PubMed  Google Scholar 

  21. Stephens B, Mueller AJ, Shering AF, Hood SH, Taggart P, Arbuthnott GW et al (2005) Evidence of a breakdown of corticostriatal connections in Parkinson’s disease. Neuroscience 132:741–754

    Article  PubMed  CAS  Google Scholar 

  22. Zaja-Milatovic S, Milatovic D, Schantz AM, Zhang J, Montine KS, Samii A et al (2005) Dendritic degeneration in neostriatal medium spiny neurons in Parkinson disease. Neurology 64:545–547

    PubMed  CAS  Google Scholar 

  23. Tremblay L, Filion M, Bedard PJ (1989) Responses of pallidal neurons to striatal stimulation in monkeys with MPTP-induced Parkinsonism. Brain Res 498:17–33

    Article  PubMed  CAS  Google Scholar 

  24. Filion M, Tremblay L, Bedard PJ (1988) Abnormal influences of passive limb movement on the activity of globus pallidus neurons in parkinsonian monkeys. Brain Res 444:165–176

    Article  PubMed  CAS  Google Scholar 

  25. De la Fuente-Fernandez R, Sossi V, Huang Z, Furtado S, Lu JQ, Calne DB et al (2004) Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: implications for dyskinesias. Brain 127:2747–2754

    Article  Google Scholar 

  26. Ballard PA, Tetrud JW, Langston JW (1985) Permanent human Parkinsonism due to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP): seven cases. Neurology 35:949–956

    PubMed  CAS  Google Scholar 

  27. Bédard PJ, Di Paolo T, Falardeau P, Boucher R (1986) Chronic treatment with l-dopa, but not bromocriptine induces dyskinesia in MPTP-parkinsonian monkeys. Correlation with [3H]spiperone binding. Brain Res 379:294–299

    Article  PubMed  Google Scholar 

  28. Pearce RK, Banerji T, Jenner P, Marsden CD (1998) De novo administration of ropinirole and bromocriptine induces less dyskinesia than l-dopa in the MPTP-treated marmoset. Mov Disord 13:234–241

    Article  PubMed  CAS  Google Scholar 

  29. Jenner P (2000) Factors influencing the onset and persistence of dyskinesia in MPTP-treated primates. Ann Neurol 47:S90–S99

    PubMed  CAS  Google Scholar 

  30. Blanchet PJ, Calon F, Martel JC, Bédard PJ, Di Paolo T, Walters RR et al (1995) Continuous administration decreases and pulsatile administration increases behavioral sensitivity to a novel dopamine D2 agonist (U-91356A) in MPTP-exposed monkeys. J Pharmacol Exp Ther 272:854–859

    PubMed  CAS  Google Scholar 

  31. Bibbiani F, Costantini LC, Patel R, Chase TN (2005) Continuous dopaminergic stimulation reduces risk of motor complications in parkinsonian primates. Exp Neurol 192:73–78

    Article  PubMed  CAS  Google Scholar 

  32. Morissette M, Goulet M, Soghomonian JJ, Blanchet PJ, Calon F, Bédard PJ et al (1997) Preproenkephalin mRNA expression in the caudate-putamen of MPTP monkeys after chronic treatment with the D2 agonist U91356A in continuous or intermittent mode of administration: comparison with l-DOPA therapy. Brain Res Mol Brain Res 49:55–62

    Article  PubMed  CAS  Google Scholar 

  33. Aubert I, Guigoni C, Hakansson K, Li Q, Dovero S, Barthe N et al (2005) Increased D1 dopamine receptor signaling in levodopa-induced dyskinesia. Ann Neurol 57:17–26

    Article  PubMed  CAS  Google Scholar 

  34. Calon F, Grondin R, Morissette M, Goulet M, Blanchet PJ, Di Paolo T et al (2000) Molecular basis of levodopa-induced dyskinesias. Ann Neurol 47:70–78

    Google Scholar 

  35. Cenci MA, Tranberg A, Andersson M, Hilbertson A (1999) Changes in the regional and compartmental distribution of FosB- and JunB-like immunoreactivity induced in the dopamine-denervated rat striatum by acute or chronic l-dopa treatment. Neuroscience 94:515–527

    Article  PubMed  CAS  Google Scholar 

  36. Calon F, Birdi S, Rajput AH, Hornykiewicz O, Bedard PJ, Di Paolo T (2002) Increase of preproenkephalin mRNA levels in the putamen of Parkinson disease patients with levodopa-induced dyskinesias. J Neuropathol Exp Neurol 61:186–196

    PubMed  CAS  Google Scholar 

  37. Boraud T, Bezard E, Bioulac B, Gross CE (2001) Dopamine agonist-induced dyskinesias are correlated to both firing pattern and frequency alterations of pallidal neurones in the MPTP-treated monkey. Brain 124:546–557

    Article  PubMed  CAS  Google Scholar 

  38. Brown P, Oliviero A, Mazzone P, Insola A, Tonali P, Di Lazzaro V (2001) Dopamine dependency of oscillations between subthalamic nucleus and pallidum in Parkinson’s disease. J Neurosci 21:1033–1038

    PubMed  CAS  Google Scholar 

  39. Juncos JL, Engber TM, Raisman R, Susel Z, Thibaut F, Ploska A et al (1989) Continuous and intermittent levodopa differentially affect basal ganglia function. Ann Neurol 25:473–478

    Article  PubMed  CAS  Google Scholar 

  40. Engber TM, Susel Z, Juncos JL, Chase TN (1989) Continuous and intermittent levodopa differentially affect rotation induced by D-1 and D-2 dopamine agonists. Eur J Pharmacol 168:291–298

    Article  PubMed  CAS  Google Scholar 

  41. Engber TM, Susel Z, Kuo S, Gerfen CR, Chase TN (1991) Levodopa replacement therapy alters enzyme activities in striatum and neuropeptide content in striatal output regions of 6-hydroxydopamine lesioned rats. Brain Res 552:113–118

    Article  PubMed  CAS  Google Scholar 

  42. Rascol O, Brooks DJ, Korczyn AD, De Deyn PP, Clarke CE, Lang AE (2000) A 5 year study of the incidence of dyskinesia in patients with early parkinson’s disease who were treated with ropinirole or levodopa. N Engl J Med 342:1484–1491

    Article  PubMed  CAS  Google Scholar 

  43. Parkinson Study Group (2000) Pramipexole versus levodopa as initial treatment for Parkinson disease. JAMA 284:231–238

    Article  Google Scholar 

  44. Whone AL, Watts RL, Stoessl AJ, Davis M, Reske S, Nahmias C et al (2003) Slower progression of Parkinson’s disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol 54:93–101

    Article  PubMed  CAS  Google Scholar 

  45. Parkinson Study Group (2002) Dopamine transporter brain imaging to assess the effects of pramipexole versus levodopa on Parkinson disease progression. JAMA 287:1653–1661

    Article  Google Scholar 

  46. Nutt JG, Obeso JA, Stocchi F (2000) Continuous dopamine receptor stimulation in advanced Parkinson’s disease. Trends Neurosci 23:109–115

    Article  Google Scholar 

  47. Stocchi F, Ruggieri S, Vacca L, Olanow CW (2002) Prospective randomized trial of lisuride infusion versus oral levodopa in PD patients. Brain 125:2058–2066

    Article  PubMed  Google Scholar 

  48. Olanow CW, Fahn S, Muenter M et al (1994) A multi-center, double-blind, placebo-controlled trial of pergolide as an adjunct to Sinemet in Parkinson’s disease. Mov Disord 9:40–47

    Article  PubMed  CAS  Google Scholar 

  49. Lieberman A, Olanow CW, Sethi K et al (1998) A multi-center double blind placebo-controlled trial of ropinirole as an adjunct to l-dopa in the treatment of Parkinson’s disease patients with motor fluctuations. Neurology 51:1057–1062

    PubMed  CAS  Google Scholar 

  50. Pinter MM, Pogarell O, Oertel WH (1999) 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 66:436–441

    Article  PubMed  CAS  Google Scholar 

  51. Clarke CE, Deane KH (2001) Cabergoline for levodopa-induced complications in Parkinson’s disease. Cochrane Database Syst Rev 1:CD001518

    PubMed  Google Scholar 

  52. Talati R, Baker WL, Patel AA, Reinhart K, Coleman CI (2009) Adding a dopamine agonist to preexisting levodopa therapy versus levodopa therapy alone in advanced Parkinson’s disease: a meta analysis. Int J Clin Pract 63:613–623

    Article  PubMed  CAS  Google Scholar 

  53. Stocchi F, Hersh BP, Scott BL, Nausieda PA, Giorgi L (2008) Ease-PD Monotherapy Study Investigators. Ropinirole 24-h prolonged release and ropinirole immediate release in early Parkinson’s disease: a randomized, double-blind, non-inferiority crossover study. Curr Med Res Opin 24:2883–2895

    Article  PubMed  CAS  Google Scholar 

  54. Rascol O, Barone P, Hauser RA et al (2010) Pramipexole Switch Study Group Efficacy, safety, and tolerability of overnight switching from immediate- to once daily extended-release pramipexole in early Parkinson’s disease. Mov Disord 25:2326–2332

    Article  PubMed  Google Scholar 

  55. Hauser RA, Schapira AH, Rascol O et al (2010) Randomized, double-blind, multicenter evaluation of pramipexole extended release once daily in early Parkinson’s disease. Mov Disord 25:2542–2549

    Article  PubMed  Google Scholar 

  56. Jankovic J, Watts RL, Martin W, Boroojerdi B (2007) Transdermal rotigotine: double-blind, placebo-controlled trial in Parkinson disease. Arch Neurol 64:676–682

    Article  PubMed  Google Scholar 

  57. Giladi N, Boroojerdi B, Korczyn AD, Burn DJ, Clarke CE, Schapira AH, SP513 investigators (2007) Rotigotine transdermal patch in early Parkinson’s disease: a randomized, double-blind, controlled study versus placebo and ropinirole. Mov Disord 22:2398–2404

    Article  PubMed  Google Scholar 

  58. Watts RL, Lyons KE, Pahwa R et al (2010) Onset of dyskinesia with adjunct ropinirole prolonged-release or additional levodopa in early Parkinson’s disease. Mov Disord 25:858–866

    Article  PubMed  Google Scholar 

  59. Pahwa R, Stacy MA, Factor SA et al (2007) EASE-PD. Ropinirole 24-h prolonged release: randomized, controlled study in advanced Parkinson disease. Neurology 68:1108–1115

    Article  PubMed  CAS  Google Scholar 

  60. Stocchi F, Giorgi L, Hunter B, Schapira AH. PREPARED: comparison of prolonged and immediate release ropinirole in advanced Parkinson’s disease. Mov Disord (in press)

  61. LeWitt PA, Lyons KE, Pahwa R, SP 650 Study Group (2007) Advanced Parkinson disease treated with rotigotine transdermal system: PREFER Study. Neurology 68:1262–1267

    Article  PubMed  CAS  Google Scholar 

  62. Poewe WH, Rascol O, Quinn N et al (2007) Efficacy of pramipexole and transdermal rotigotine in advanced Parkinson’s disease: a double-blind, double-dummy, randomised controlled trial. Lancet Neurol 6:513–520

    Article  PubMed  CAS  Google Scholar 

  63. Trenkwalder C, Kies B, Rudzinska M et al (2011) Rotigotine effects on early morning motor function and sleep in Parkinson’s disease: A double-blind, randomized, placebo-controlled study (RECOVER). Mov Disord 1:90–99

    Article  Google Scholar 

  64. Stocchi F (2005) Pathological gambling in Parkinson’s disease. Lancet Neurol 4:590–592

    Article  PubMed  Google Scholar 

  65. Driver-Dunckley E, Samanta J, Stacy M (2003) Pathological gambling associated with dopamine agonist therapy in Parkinson’s disease. Neurology 61:422–423

    PubMed  CAS  Google Scholar 

  66. Nirenberg MJ, Waters C (2006) Compulsive eating and weight gain related to dopamine agonist use. Mov Disord 21:524–529

    Article  PubMed  Google Scholar 

  67. Brodsky MA, Godbold J, Roth T, Olanow CW (2003) Sleepiness in Parkinson’s disease: a controlled study. Mov Disord 18:668–672

    Article  PubMed  Google Scholar 

  68. Zanettini R, Antonini A, Gatto G et al (2007) Valvular heart disease and the use of dopamine agonists for Parkinson’s disease. N Engl J Med 35:639–646

    Google Scholar 

Download references

Conflict of interest

F. Stocchi has received honoraria and consulting fees from GlaxoSmithKline, Boehringer Ingelheim, Orion Novartis, Teva-Lundbeck, Newron, Merck-Serono and Pfizer.

Author information

Authors and Affiliations

  1. Institute of Neurology, Institute for Research and Medical Care IRCCS “San Raffaele”, Via della Pisana 235, 00163, Rome, Italy

    Fabrizio Stocchi

Authors
  1. Fabrizio Stocchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabrizio Stocchi.

Additional information

This article is part of a supplement sponsored by GlaxoSmithKline.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stocchi, F. Continuous dopaminergic stimulation and novel formulations of dopamine agonists. J Neurol 258 (Suppl 2), 316–322 (2011). https://doi.org/10.1007/s00415-011-6024-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-011-6024-y

Keywords

Search

Navigation