CNS Drugs

, Volume 12, Issue 6, pp 485–497 | Cite as


A Review of its Efficacy in the Treatment of Parkinson’s Disease
Adis Drug Evaluation



The dopamine agonist cabergoline has been most widely studied as an adjuvant to levodopa/carbidopa therapy in patients with advanced Parkinson’s disease experiencing response fluctuations (‘wearing-off’ and ‘on-off’ phenomena) to long term levodopa therapy. Significant improvements in Unified Parkinson’s Disease Rating Scale (UPDRS) scores for motor function and activities of daily living were observed with cabergoline in a placebo-controlled study in this patient group. In addition, cabergoline significantly reduced ‘off’ time compared with placebo after 12 and 24 weeks’ therapy. The requirement for levodopa to control symptoms of Parkinson’s disease is reduced in patients given adjuvant cabergoline; however, the duration of this effect remains unclear. To date, adjuvant cabergoline has been shown to control the symptoms of advanced Parkinson’s disease for periods of up to 3 years in noncomparative studies.

Data indicate that cabergoline is at least as effective as bromocriptine in this patient group. Limited data indicate that it is more effective than pergolide in controlling certain disabilities associated with long term levodopa therapy (specifically nocturnal disabilities and motor function during the ‘off’ period).

In patients with early Parkinson’s disease, de novo therapy with cabergoline was associated with a significantly lower risk of developing motor complications after 5 years than de novo levodopa/carbidopa therapy in a single trial. The incidence of motor complications (≥1) in patients randomised to receive cabergoline (± levodopa/carbidopa as required) was 22.3 versus 33.7% in patients given only levodopa/carbidopa (p < 0.05). After 5 years, 64% of cabergoline recipients required additional levodopa/carbidopa; however, the dosage was significantly lower than that given to patients receiving only levodopa/carbidopa. UPDRS motor function scores were better in the levodopa/carbidopa group.

The tolerability profile of cabergoline appears typical of a dopamine agonist. CNS disturbances (including visual hallucinations, confusion, dizziness/light-headedness, increased libido, increased dyskinesias, insomnia and somnolence) and gastric upset are the most common events, but are rarely severe. Clinical trials indicate that the tolerability of cabergoline is similar to that of bromocriptine, but may be better than pergolide.

Conclusions: Cabergoline is useful for controlling symptoms in patients with advanced Parkinson’s disease experiencing response fluctuations to long term levodopa therapy. Importantly, it appears to be valuable as de novo therapy in patients with early disease in terms of reducing the risk of motor complications. Its long elimination half-life (63 to 68 hours) and long duration of action, which allow once daily administration, may prove advantageous in terms of attaining maximal symptom control.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Montastruc JL, Rascol O, Senard JM. Current status of dopamine agonists in Parkinson’s disease management. Drugs 1993 Sep; 46: 384–93PubMedCrossRefGoogle Scholar
  2. 2.
    Obeso JA, Grandas F, Vaamonde J, et al. Motor complications associated with chronic levodopa therapy in Parkinson’s disease. Neurology 1989; 39 Suppl. 2: 11–9Google Scholar
  3. 3.
    Yahr MD. Parkinson’s disease: new approaches to diagnosis and treatment. Acta Neurol Scand 1993; 146: 22–5Google Scholar
  4. 4.
    Schelosky L, Poewe W. Current strategies in the drug treatment of advanced Parkinson’s disease — new modes of dopamine substitution. Acta Neurol Scand 1993; 87 Suppl. 146: 46–9Google Scholar
  5. 5.
    Schuh LA, Bennett JP. Suppression of dyskinesias in Parkinson’s disease: continuous intravenous levodopa shifts the dose-response for production of dyskinesias but not relief of parkisonism in patients with advanced Parkinson’s disease. Neurology 1993; 43: 1545–50PubMedCrossRefGoogle Scholar
  6. 6.
    Stocchi F. Dopamine agonists in Parkinson’s disease: what is theirrole in early treatment? CNS Drugs 1998 Sep; 10: 159–70CrossRefGoogle Scholar
  7. 7.
    Poewe W. Adjuncts to levodopa therapy: dopamine agonists. Neurology 1998 Jun; 50 Suppl. 6: 23–6CrossRefGoogle Scholar
  8. 8.
    Ogawa N. Early introduction of dopamine agonists in the long-term treatment of Parkinson’s disease. Neurology 1998 Aug; 51 Suppl. 2: 13–20CrossRefGoogle Scholar
  9. 9.
    Durif F. Treating and preventing levodopa-induced dyskinesias: current and future strategies. Drugs Aging 1999 May; 14:337–45PubMedCrossRefGoogle Scholar
  10. 10.
    Farmitalia Carlo Erba. Milan, Italy. (Data on file)Google Scholar
  11. 11.
    Strolin Benedetti M, Dostert P, Barone D, et al. In vivo interaction of cabergoline with rat brain dopamine receptors labelled with [3H]N-n-propylnorapomorphine. Eur J Pharmacol 1990 Oct 23; 187:399–408CrossRefGoogle Scholar
  12. 12.
    Di Salle E, Ornati G, Briatico G. FCE 21336, a new ergoline derivative with a potent and long-acting lowering effect on prolactin secretion in rats. J Endocrinol Invest 1982; 5: 45Google Scholar
  13. 13.
    Di Salle E, Ornati G, Giuduci D, et al. Prolactin lowering effect of a new ergoline derivative, FCE 21336, in the rat: a comparison with bromocriptine. Acta Endocrinol 1983; 103: 265Google Scholar
  14. 14.
    Fariello RG, Carfagna N, Buonamici M, et al. Cabergoline: a long-acting D-2 agonist with antiparkinsonian properties -preclinical studies [abstract]. Ann Neurol 1991 Aug; 30: 258Google Scholar
  15. 15.
    Pontiroli AE, Viberti GC, Mangili R, et al. Selective and extremely long inhibition of prolactin release in man by 1-ethyl-3-(3′-dimethylaminopropyl)-3-(6′allylergoline-8′-β-carboyl) urea-diphospate (FCE 21336). Br J Clin Pharmacol 1987; 1987: 433–8CrossRefGoogle Scholar
  16. 16.
    McArthur RA, Brughera M, Cervini MA, et al. The effects of the D2 agonist cabergoline on MPTP-induced parkinsonism in monkeys. In: Beninger RJ, Palomo T, Archer T, editors. Dopamine disease states: strategies for studying brain disorders. Madrid: CYM, 1996: 67–81Google Scholar
  17. 17.
    Arai N, Isaji M, Miyata H, et al. Differential effects of three dopamine receptor agonists in MPTP-treated monkeys. J Neural Transm Park Dis Dement Sect 1995; 10(1): 55–62PubMedCrossRefGoogle Scholar
  18. 18.
    Fradriksson A, Bassen M, Caccia C, et al. Effects of dopamine agoinists upon locomotor function in denervated mice and rats: comparison with cabergoline. In: Beninger RJ, Palomo T, Archer T, editors. Dopamine disease states: strategies for studying brain disorders. Madrid: CYM, 1996: 181–210Google Scholar
  19. 19.
    Pianezzola E, Bellotti V, Lacroix R, et al. Determination of cabergoline in plasma and urine by high-performance liquid chromatography with electrochemical detection. J Chromatogr Biomed Appl 1992 Feb 7; 574: 170–4CrossRefGoogle Scholar
  20. 20.
    Persiani S, Pianezzola E, Broutin F, et al. Radioimmunoassay for the synthetic ergoline derivative cabergoline in biological fluids. J Immunoassay 1992; 13(3): 457–76PubMedCrossRefGoogle Scholar
  21. 21.
    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: 841–5PubMedCrossRefGoogle Scholar
  22. 22.
    Lera G, Vaamonde J, Rodriguez M, et al. Cabergoline in Parkinson’s disease: long-term follow-up. Neurology 1993 Dec; 43: 2587–90PubMedCrossRefGoogle Scholar
  23. 23.
    Persiani S, Rocchetti M, Pacciarini MA, et al. The effect of food on cabergoline pharmacokinetics and tolerability in healthy volunteers. Biopharm Drug Dispos 1996; 17: 443–55PubMedCrossRefGoogle Scholar
  24. 24.
    Strolin Benedetti M, Dostert P, Dordain G, et al. Cabergoline: metabolism, disposition and lack of pharmacokinetic interaction with selegiline [abstract]. 1st International Meeting Old and New Dopamine Agonists in Parkinson’s Disease: 1993 Dec 12–14; Pisa, ItalyGoogle Scholar
  25. 25.
    Battaglia R, Strolin Benedetti M, Mantegani S, et al. Disposition and urinary metabolic pattern of cabergoline, a potent dopa-minergic agonist, in rat, monkey and man. Xenobiotica 1993 Dec; 23: 1377–89PubMedCrossRefGoogle Scholar
  26. 26.
    Cocchiara G, Strolin Benedetti M. Excretion balance and urinary metabolic pattern of 3H cabergoline in man. Drug Metabol Drug Interact 1992; 10: 199–211PubMedCrossRefGoogle Scholar
  27. 27.
    Marsden CD, Parkes JD, Quinn N. Fluctuations in disability in Parkinson’s disease: clinical aspects. In: Marsden CD, Fahn S, editors. Movement disorders. London: Butterworths, 1982: 96–122Google Scholar
  28. 28.
    Fahn S, Elton RL, Members of the UPDRS Development Committee. Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB, et al., editors. Recent developments in Parkinson’s disease. Vol. 2. Florham Park (NJ): MacMillan Healthcare Information, 1987: 153–63Google Scholar
  29. 29.
    Jori MC, Franceschi M, Giusti MC, et al. Clinical experience with cabergoline, a new ergoline derivative, in the treatment of Parkinson’s disease. Adv Neurol 1990; 53: 539–43PubMedGoogle Scholar
  30. 30.
    Ahlskog JE, Muenter MD, Maraganore DM, et al. Fluctuating Parkinson’s disease: treatment with the long-acting dopamine agonist cabergoline. Arch Neurol 1994 Dec; 51: 1236–41PubMedCrossRefGoogle Scholar
  31. 31.
    Hutton JT, Morris JL, Brewer MA. Controlled study of the antiparkinsonian activity and tolerability of cabergoline. Neurology 1993 Mar; 43: 613–6PubMedCrossRefGoogle Scholar
  32. 32.
    Lieberman A, Imke S, Muenter M, et al. Multicenter study of cabergoline, a long-acting dopamine receptor agonist, in Parkinson’s disease patients with fluctuating responses to levodopa/carbidopa. Neurology 1993 Oct; 43: 1981–4PubMedCrossRefGoogle Scholar
  33. 33.
    Yanagisawa N, Kowa H, Mizuno Y, et al. Early phase II study of CG-101 (cabergoline) in Parkinson’s disease [in Japanese]. Rinsho Iyaku 1996; 12(10): 2063–91Google Scholar
  34. 34.
    Yanagisawa N, Kowa H, Mizuno Y, et al. Clinical evaluation of CG-101 (cabergoline) in patients with Parkinson’s disease: results of late phase II study [in Japanese]. Rinsho Iyaku 1996; 12(17): 3665–718Google Scholar
  35. 35.
    Ahlskog JE, Wright KF, Muenter MD, et al. Adjunctive cabergoline therapy of Parkinson’s disease: comparison with placebo and assessment of dose responses and duration of effect. Clin Neuropharmacol 1996 Jun; 19: 202–12PubMedCrossRefGoogle Scholar
  36. 36.
    Hutton JT, Koller WC, Ahlskog JE, et al. Multicenter, placebocontrolled trial of cabergoline taken once daily in the treatment of Parkinson’s disease. Neurology 1996 Apr; 46: 1062–5PubMedCrossRefGoogle Scholar
  37. 37.
    Steiger MJ, El Debas T, Anderson T, et al. Double-blind study of the activity and tolerability of cabergoline versus placebo in parkinsonians with motor fluctuations. J Neurology 1996 Jan; 243: 68–72CrossRefGoogle Scholar
  38. 38.
    Yanagisawa N, Kowa H, Mizuno Y, et al. Long-term clinical study of CG-101 (cabergoline) in Parkinson’s disease [in Japanese]. Rinsho Iyaku 1996; 12(17): 3799–823Google Scholar
  39. 39.
    Inzelberg R, Nisipeanu P, Rabey MJ, et al. Long-term tolerability and efficacy of cabergoline, a new long-acting dopamine agonist, in Parkinson’s disease. Mov Disord 1995 Sep; 10: 604–7PubMedCrossRefGoogle Scholar
  40. 40.
    Chaudhuri KR, Bhattacharya K, Agapito C, et al. The use of cabergoline in nocturnal Parkinsonian disabilities causing sleep disruption. A comparative study with controlled-release levodopa. Eur Neurol 1999. In pressGoogle Scholar
  41. 41.
    Yanagisawa N, Kowa H, Mizuno Y, et al. The clinical evaluation of CG-101 (cabergoline) in Parkinson’s disease with combined use of L-DOPA: a multi-centere double-blind comparative study vs. bromocriptine mesilate [in Japanese]. Rinsho Iyaku 1996; 12(17): 3757–98Google Scholar
  42. 42.
    Inzelberg R, Nisipeanu P, Rabey JM, et al. Double-blind comparison of cabergoline and bromocriptine in Parkinson’s disease patients with motor fluctuations. Neurology 1996 Sep; 47: 785–8PubMedCrossRefGoogle Scholar
  43. 43.
    Destee A, Schneider E, Gershanik O, et al. Efficacy and tolerability of cabergoline compared to bromocriptine in patients suffering from levodopa associated motor complications (not on treatment with DA-agents) [abstract]. Mov Disord 1996; 11 Suppl. 1: 269Google Scholar
  44. 44.
    Chaudhuri KR, Gathani T, Agapito C, et al. Comparative study of the effect of pergolide and cabergoline on nocturnal disabilities in Parkinson’s disease: a single blind study [abstract no. P-TU-081]. Parkinsonism & Related Disorders 1999; 5: S69CrossRefGoogle Scholar
  45. 45.
    Ulm G, Schüler P, MODAC study group. Cabergoline versus pergolide: a video-blinded, randomized, multicenter crossover study. Aktuel Neurol 1999. In pressGoogle Scholar
  46. 46.
    Rinne UK, Bracco F, Chouza C, et al. Cabergoline in the treatment of early Parkinson’s disease: results of the first year of treatment in a double-blind comparison of cabergoline and levodopa. Neurology 1997 Feb; 48: 363–8PubMedCrossRefGoogle Scholar
  47. 47.
    Rinne UK, Bergamasco B, Mamoli A, et al. A five-year double-blind study with cabergoline versus levodopa [abstract]. 13th International Congress on Parkinson’s Disease: 1999 Jul 24–28; Vancouver, CanadaGoogle Scholar
  48. 48.
    Bhatt MH, Keenan SP, Fleetham JA. Pleuropulmonary disease associated with dopamine agonist therapy. Ann Neurol 1991 Oct; 30: 613–6PubMedCrossRefGoogle Scholar
  49. 49.
    Frans E, Dom R, Demedts M. Pleuropulmonary changes during treatment of Parkinson’s disease with a long-acting ergot derivative, cabergoline. Eur Respir J 1992 Feb; 5: 263–5PubMedGoogle Scholar
  50. 50.
    Ling LH, Ahlskog JE, Munger TM, et al. Constrictive pericarditis and pleuropulmonary disease linked to ergot dopamine agonist therapy for Parkinson’s disease. Mayo Clin Proc 1999; 74: 371–5PubMedCrossRefGoogle Scholar
  51. 51.
    Cavallini A, Micieli G, Martignoni E, et al. Cardiopressor effects of short-term treatment with cabergoline in 1-Dopa stable responder parkinsonian patients:relevance of postprandial hypotension. Clin Neuropharmacol 1991 Aug; 14: 343–51PubMedCrossRefGoogle Scholar
  52. 52.
    British National Formulary. Cabergoline. London: The Pharmaceutical Press, 1999 Sep: 231Google Scholar
  53. 53.
    Pharmacia & Upjohn. Cabaser Prescribing Information. Tokyo: Pharmacia & Upjohn, 1999Google Scholar
  54. 54.
    Olanow CW, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease: treatment guidelines. Neurology 1998; 50 Suppl. 3: S1–57PubMedCrossRefGoogle Scholar
  55. 55.
    Lees AJ, Stern GM. Sustained bromocriptine therapy in previously untreated patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 1981; 44: 1020–3PubMedCrossRefGoogle Scholar
  56. 56.
    Gimenez-Roldan S, Tolosa E, Burguera JA, et al. Early combination of bromocriptine and levodopa in Parkinson’s disease: a prospective randomised study of 2 parallel groups over a total follow-up period of 44 months including an initial 8 months double-blind stage. Clin Neuropharmacol 1997; 20: 67–76PubMedCrossRefGoogle Scholar
  57. 57.
    Montastruc JL, Rascol O, Sennard JM, et al. A randomised control study of bromocriptine versus levodopa in previously untreated parkinsonian patients: a 3-year follow-up. J Neurol Neurosurg Psychiatry 1989; 52: 773–5PubMedCrossRefGoogle Scholar
  58. 58.
    Ahlskog JE. Treatment approaches for early Parkinson’s disease. In: Factor SA, Weiner WJ, editors. Parkinson’s disease at the millenium. New York: Demos Vermande, 2000. In pressGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

Personalised recommendations