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Ropinirole and Pramipexole, the New Agonists

Published online by Cambridge University Press:  02 December 2014

Douglas E. Hobson ,
Emmanuelle Pourcher  and
W.R. Wayne Martin
Douglas E. Hobson
Affiliation:
The University of Manitoba, Winnipeg, Manitoba
Emmanuelle Pourcher
Affiliation:
Laval University, Quebec City, Quebec
W.R. Wayne Martin
Affiliation:
University of Alberta, Edmonton, Alberta
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Abstract

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Ropinirole and pramipexole are non-ergoline dopamine agonists which are relatively specific for the D2 family of dopamine receptors. They have side-effect profiles linked to peripheral and central dopaminergic stimulation, amenable to tolerance through a slow titration or the addition of domperidone in sensitive patients. They do not have the uncommon but problematic ergot-related side effects of bromocriptine and pergolide. Ropinirole and pramipexole have both been shown to be efficacious when used as monotherapy in early Parkinson's disease (PD), and have been suggested as being less likely than levodopa to lead to the early development of motor fluctuations and dyskinesias in this clinical setting. They have also been shown to be useful as adjunctive therapy to levodopa in advanced PD and to have a levodopa-sparing effect in these patients. Dose equivalents amongst the available dopamine agonists is difficult to know with certainty but has been estimated as follows: 30 mg of bromocriptine, 15 mg of ropinirole, 4.5 mg of pramipexole, and 3.0 mg of pergolide

Résumé

RÉSUMÉ

Le ropinirole et le pramipexole sont des agonistes dopaminergiques non dérivés de l'ergot, qui sont relativement spécifiques pour les récepteurs dopaminergiques de la famille D2. Ils ont des profils d'effets secondaires reliés à la stimulation dopamin-ergique périphérique et centrale, et une augmentation progressive de la posologie ou l'addition de dompéridone chez les patients sensibles favorise la tolérance. Ils n'ont pas les effets secondaires rares et problématiques, reliés à l'er-got, de la bromocriptine et du pergolide. Il a été démontré que le ropinirole et le pramipexole sont tous deux efficaces en monothérapie dans la maladie de Parkinson (MP) au début, et il semble qu'ils aient moins tendance que la lévodopa à provoquer l'apparition précoce de fluctuations motrices et de dyskinésies dans ce contexte clinique. On a également démontré qu'ils sont utiles comme traitement adjuvant à la lévodopa dans la MP en phase avancée et qu'ils ont un effet d'épargne de la lévodopa chez ces patients. Il est difficile de déterminer avec certitude les doses équivalentes des agonistes dopaminergiques disponibles, mais elles ont été estimées comme suit: bromocriptine 30 mg, ropinirole 15 mg, pramipexole 4.5 mg et pergolide 3.0 mg.

Information

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 26 , Issue S2 , August 1999 , pp. S27 - S33
Copyright
Copyright © The Canadian Journal of Neurological 1999

References

1. Ehiinger, H, Hornykiewicz, O. Verteilung von Noradrenalin und Dopamin (3-hydroxytyramin) im Gerhirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyraminalen Systems. Klin Wschr. 1960; 38: 1236.Google Scholar
2. Barbeau, A, Sourkes, TL, Murphy, GR: Les catecholamines dans la maladie de Parkinson. In: De Ajuriaguerra, J (ed): Monoamines et Systeme Nerveux Central. Paris: Masson: 1962: 247–262.Google Scholar
3. Cotzias, GC, Van Woert, MH, Schiffer, LM. Aromatic amino acids and modification of Parkinsonism. N Engl J Med 1967; 276: 374–379.Google Scholar
4. Uitti, RJ, Ahlskog, JE, Maragamore, DM, et al. Levodopa therapy and survival in idiopathic Parkinson’s disease: Olmstead County Project. Neurology 1993; 43: 1918–1926.Google Scholar
5. Fahn, S. Adverse effects of levodopa in Parkinson’s Disease. In: Calne, DB, ed. Drugs for the Treatment of Parkinson’s Disease (Handbook of Experimental Pharmacology). Berlin, Heidelberg: Springer Verlag 1989; 88: 443–438.Google Scholar
6. Juncos, JL, Engber, TM, Raisman, R, et al. Continuous and intermittant levodopa differentially affect basal ganglia function. Ann Neurol 1989; 25: 473–478.Google Scholar
7. Nutt, JG. Levodopa-induced dyskinesia. Neurology 1990; 40: 340–345.Google Scholar
8. Olanow, CW. Oxidation reactions in Parkinson’s disease. Neurology 1990; 40 (Suppl 3): 32–37.Google Scholar
9. Fahn, S, Cohen, G. The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 1992; 32: 804–812.CrossRefGoogle Scholar
10. Micel, PP, Hefti, F. Toxicity of 6-hydroxydopamine and dopamine for dopaminergic neurons in culture. J Neurosci Res 1990; 26: 428–435.Google Scholar
11. Mena, MA, Pardo, B, Casarejos, MJ, Fahn, S, Garcia de Yebenes, J. Neurotoxicity of levodopa on catecholamine-rich neurons. Mov Disord 1992; 7: 23–31.Google Scholar
12. Agid, Y. Levodopa: is toxicity a myth? Neurology 1998; 50: 858–863.Google Scholar
13. Olanow, CW. Single-blind double crossover-controlled study of carbidopa/levodopa vs. BCT in untreated Parkinson patients. Arch Neurol 1988; 45: 206.Google Scholar
14. Mizuno, Y, Kondo, T, Narabayashi, H. Pergolide in the treatment of Parkinson’s disease. Neurology 1995; 45(Suppl3): S13-S21.Google Scholar
15. Quinn, N. Drug treatment of Parkinson’s disease. Br Med J 1995; 310: 575–579.Google Scholar
16. Eisle, T, Hall, RP, Kalavar, KA, et al. Erythromelalgia-like eruption in Parkinsonian patients treated with bromocriptine. Neurology 1982; 32: 577–583.Google Scholar
17. Todman, DH, Oliver, WA, Edward, R.L. Pleuropulmonary fibrosis due to bromocriptine treatment for Parkinson’s disease. Clin Exp Neurol 1990; 27: 79–82.Google Scholar
18. Jimenez-Jiminez, FJ, Lopez-Alvarez, J, Sanchez-Chapado, M, et al. Retroperitoneal fibrosis in a patient with Parkinson’s disease treated with pergolide. Clin Neuropharmacol 1995; 18: 277–279.Google Scholar
19. Eden, RJ, Costall, B, Domeney, AM, et al. Preclinical pharmacology of ropinirole (SKF101468-A), a novel dopamine D2 agonist. Pharmacol Biochem Behaviour 1991; 38: 147–154.Google Scholar
20. Bowen, WP, Coldwell, MC, Hicks, FR, Riley, GJ, Fears, R. Ropinirole, a novel dopaminergic agent for the treatment of Parkinson’s disease, with selectivity for cloned D2 receptors. Br J Pharmacol 1993; 110 (Suppl): 93p.Google Scholar
21. Tulloch, I. Pharmacologic profile of ropinirole: a nonergoline dopamine agonist. Neurology 1997; 49 (Suppl 1): S58-S62.Google Scholar
22. Sautel, F, Griffon, N, Levesque, D, et al. A functional test identifies dopamine agonists selective for D3 versus D2 receptors. Neuroreport 1995; 6: 329–332.CrossRefGoogle ScholarPubMed
23. Mierau, J, Schingnitz, G. Biochemical and pharmacological studies on prampipexole, a potent and selective dopamine D2 receptor agonist. Eur J Pharmacol 1992; 215: 161–170.Google Scholar
24. Mierau, J, Schneider, FJ, Ennsinger, HA, et al. Pramipexole binding and activation of cloned and expressed dopamine D2,D3, and D4 receptors. Eur J Pharmacol 1995; 29: 290.Google Scholar
25. Willner, P, Lappas, S, Cheeta, S, et al. Reversal of stress-induced anhedonia by the dopamine receptor agonist, pramipexole. Psychopharmacol 1994; 115: 454–462.Google Scholar
26. Gerfen, CR. Dopamine function in the striatum: implications for dopamine receptor agonist treatment of Parkinson’s disease. In: Olanow, CW, Obeso, JA, eds. Beyond the Decade of the Brain: Dopamine Agonists in Early Parkinson’s Disease 1997; 2: 55–74.Google Scholar
27. Boothman, BR, Spokes, EG, Pharmacokinetic data for ropinirole. Lancet 1990; 336: 814.CrossRefGoogle ScholarPubMed
28. Brefel, C. et al. Effect of food on the pharmacokinetics of ropinirole in parkinsonian patients. Br J Clin Pharmacol. 1998; 45: 412–415.Google Scholar
29. Bloomer, JC, Clark, SE, Cherney, RJ. In vitro identification of the P450 enzymes responsible for the metabolism of ropinirole. Drug Metab Dispos 1997; 25: 840–844.Google Scholar
30. Schilling, C, Haselbarth, V. SND 919 increasing dose or study in health volunteers after oral administration. Boehringer Ingelheim, Germany (unpublished report U89-0039/836.001), Nov. 1988.Google Scholar
31. Haselbarth, V, et. al. SND 919 CL 2 Y: Pharmocokinetics and bioavailability of SND 919 CL 2Y, comparison of the plasma levels after intravenous (infusion 100 mcg), oral (tablets, 300 mcg) and oral (solution, 300 mcg) administration in 12 healthy volunteers (3-fold cross-over). Germany (unpublished report U91-0026/836.005), Sept 28, 1990.Google Scholar
32. Kiorpes, AL. Two-week oral drug interaction study with SND 919, Eldepryl and Sinemet in rhesus monkeys. Internal report, Boehringer Ingelheim, U91-022,1990.Google Scholar
33. Bedard, PJ, Gomez-Mancilla, B, Blanchet, P, et al. Dopamine agonists as a first line therapy of parkinsonism in MPTP monkeys. In: Olanow, CW, Obeso, JA, eds. Beyond the Decade of the Brain: Dopamine Agonists in Early Parkinson’s Disease. 1997; 2: 101–110.Google Scholar
34. Rinne, UK Dopamine agonists as primary treatment in Parkinson’s disease. Adv Neurol 1986; 45: 519–523.Google Scholar
35. Tulloch, IF. Pharmacologic profile of ropinirole: a nonergoline dopamine agonist. Neurology 1997; 49(Suppl 1): S58-S62.Google Scholar
36. Olanow, CW. Attempts to obtain neuroprotection in Parkinson’s disease. Neurology 1997; 49 (Suppl 1): S26-S33.CrossRefGoogle ScholarPubMed
37. Pearce, RKB, Banerji, T, Jenner, P, Marsden, CD. De novo administration of ropinirole and bromocriptine induces less dyskinesia than L-dopa in the MPTP-treated marmoset. Mov Disord 1998; 13: 234–241.Google Scholar
38. Brooks, DJ, Turjanski, N, Burn, DJ. Ropinirole in the symptomatic treatment of Parkinson’s disease. J Neural Transm 1995;45(Suppl): 231–238.Google Scholar
39. Fahn, S, Elton, RL, Members of the UPDRS Development Committee. Unified Parkinson’s Disease Rating Scale. In: Fahn, S, Marsden, CD, Goldstein, M, Calne, DB eds. Recent Developments in Parkinson’s Disease. New York; Macmillan, 1987: 153–163.Google Scholar
40. Kreider, MS, Wilson-Lynch, K, Gardiner, DE, Wheadon, DE. A double blind, placebo controlled extension study to evaluate the 12-month efficacy and safety of ropinirole in early Parkinson’s disese. Neurology 1997; 48 (Suppl 2): A269.Google Scholar
41. Adler, CH, Sethi, KD, Hauser, RA, et al. Ropinirole for the treatment of early Parkinson’s Disease. Neurology 1997; 49: 393–399.CrossRefGoogle ScholarPubMed
42. Rascol, O, Brooks, D, Brunt, ER, et al. Ropinirole in the treatment of early Parkinson’s disease: a 6-month interim report of a 5 year levodopa-controlled study. Mov Disord 1998; 13: 39–45.Google Scholar
43. Korczyn, M, Brooks, DJ, Brunt, ER, et al. Ropinirole versus bromocriptine in the treatment of early Parkinson’s disease: a 6-month interim report of a 3-year study. Mov Disord 1998; 13: 46–51.Google Scholar
44. Hubble, JP, Koller, WC, Cutler, NR, et al. Pramipexole in patients with early Parkinson’s disease. Clin Neuropharmacol 1995; 18: 338–347.Google Scholar
45. Parkinson’s Study Group. Safety and efficacy of pramipexole in early Parkinson’s disease: a randomized dose ranging study. JAMA 1997; 278: 125–130.Google Scholar
46. Shannon, KM, Bennett, Jr, Freidman, JH, et al. Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson’s disease. Neurology 1997; 49: 724–728.CrossRefGoogle ScholarPubMed
47. 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: 234–245.CrossRefGoogle ScholarPubMed
48. Kreider, M, Knox, S, Gardiner, D, et al. A multicenter double blind study of ropinirole as an adjunct to L-dopa in Parkinson’s disease. Neurology 1996; 46(Suppl 2): 475.Google Scholar
49. Ropinirole 043 study group. A double blind comparative study of ropinirole versus bromocriptine in the treatment of parkinsonian patients not optimally controlled on L-dopa. Mov Disord 1996; 11(Suppl 1): 188.Google Scholar
50. Mohlo, ES, Factor, SA, Weiner, WJ, et al. The use of pramipexole, a novel dopamine (DA) agonist, in advancd Parkinson’s disease. J Neural Transm 1995; (S)45: 225–230.Google Scholar
51. 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: 162–168.CrossRefGoogle ScholarPubMed
52. Guttman, M, and the International Pramipexole-Bromocriptine Study Group. Double blind comparison of bromocriptine treatment with placebo in advanced Parkinson’s disease. Neurology 1997; 49: 1060–1065.Google Scholar
53. Hauser, R, Zesiewicz, T. Parkinson’s Disease: Questions and Answers 2nd ed. (ed.). Merit Publishing International. 1997: 66.Google Scholar