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The Place of the Dopaminergic Agonists in the Treatment of Parkinson’s Disease: the View from the Trenches

Published online by Cambridge University Press:  18 September 2015

David B. King*
Affiliation:
Division of Neurology, Department of Medicine, University of Dalhousie, Halifax
*
Suite 100, Sommerset Place, 1030 South Park Street, Halifax, Nova Scotia, Canada B3H 2S3
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Abstract:

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The use of the dopamine receptor agonists in Parkinson’s disease has a compelling logic. These agents are supposed to act independently of the dying cells of the substantia nigra directly on the cells of the striatum. Early clinical trials in advanced disease were only mildly impressive. Later they were found to be beneficial in early disease but their effectiveness waned. Their ultimate failure may reflect the fact that the majority of current agents do not stimulate D1 and D2 receptors in a physiologic ratio. The drugs may act presynaptically and with the eventual loss of the anatomic relationships between nigra and striatum the drugs fail. There is, however, a rationale to their current use. When used along with L-Dopa in early disease the development of late-stage fluctuations are reduced with the same anti-parkinsonian benefits. Merging this concept with the demonstrated effect of selegiline in slowing the course of the disease, the current practice of triple therapy with selegiline, L-Dopa and a dopamine receptor agonist emerges.

Type
Research Article
Copyright
Copyright © Canadian Neurological Sciences Federation 1992

References

1.Lieberman, AN, Zolfaghari, M, Bol, D, et al. The anti-parkinsonian efficacy of bromocriptine. Neurology 1976; 26: 405.CrossRefGoogle Scholar
2.Lieberman, AN, Gopinathan, G, Nelphytides, A, et al. Dopamine agonists in Parkinson’s disease. In: Stern, G, ed. Parkinson’s Disease. Baltimore: John Hopkins, 1990: 509535.Google ScholarPubMed
3.Rinne, UK.Combined bromocriptine – levadopa therapy early in Parkinson’s disease. Neurology 1985; 35: 11961198.CrossRefGoogle Scholar
4.Schran, HF, Bhuta, SI, Schwartz, HJ.The pharmacokinetics of bromocriptine in man. In: Goldstein, M, ed. Ergot Compounds and Brain Function: Neuroendocrine and Neuropsychiatric Aspects. New York: Raven Press, 1980: 125139.Google Scholar
5.Goldstein, M, Lew, JY, Sauter, A, et al. The affinities of ergot compounds for dopamine agonist and dopamine antagonist receptor sites. In: Goldstein, M, ed. Ergot Compounds and Brain Functions: Neuroendocrine and Neuropsychiatric Aspects. New York: Raven Press, 1980: 7582.Google ScholarPubMed
6.Horowski, R.Differences in the dopaminergic effects of the ergot derivatives bromocryptine, lisuride and D-LSD as compared with apomorphine. Eur J Pharmacol 1978; 51: 157166.CrossRefGoogle ScholarPubMed
7.Korf, J, van der Heyden, JAM, Westerink, BHC.Coordination of dopaminergic processes in the striatum and the role of presynaptic lateral inhibition. In: Cols, AR, Lohman, AHM, van den Bercken, JHL, eds. Psychobiology of Striatum. Amsterdam: Elsevier, 1977:5159.Google Scholar
8.Westerink, BHC.Regional dopamine metabolism in the rat brain. Thesis, University of Groningen, 1977.Google Scholar
9.Bjorklund, A, Lindvall, O.Dopamine-containing systems in the CNS. In: Bjorklund, A, Hokfelt, T, eds. Classical Transmitters in the CNS, Part 1. Handbook of Chemical Neuroanatomy 2, London: Elsevier, 1984: 55122.Google Scholar
10.Moore, RY, Bloom, FE.Central catecholamine neuron systems: anatomy and physiology of the dopamine systems. Ann Rev Neurosci 1978; 1: 129.CrossRefGoogle ScholarPubMed
11.Nauta, WJH, Domesick, VB.Afferent and efferent relationships of the basal ganglia. In: Evered, D, O’Connor, M, eds. Functions of the Basal Ganglia, CIBA Foundation Symposium 107. London: Pittman, 1984:323.Google Scholar
12.Szabo, J.Striatonigral and nigrostriatal connections. Appl Neurophysiol 1979; 42: 9.Google Scholar
13.Rinne, UK.Combination of a dopamine agonist, M.A.O-D inhibitor and levadopa – a new strategy in the treatment of early Parkinson’s disease. Acta Neurol Scand 1989; 126: 165169.CrossRefGoogle Scholar
14.Quinn, N, Parkes, JD, Marsden, CD.Control of on/off phenomenon by continuous intravenous infusion of levodopa. Neurology 1984; 34: 11311136.CrossRefGoogle Scholar
15.The Parkinson study group: effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1989; 321: 13641371.CrossRefGoogle Scholar
16.Cedarbaum, JM, Clark, M, Toy, LH, et al. Sustained release PHNO in the treatment of Parkinson’s disease: evidence for tolerance to a selective D2-receptor agonist administered as a long-acting formulation. Mov Disord 1990; 5: 298303.CrossRefGoogle ScholarPubMed
17.Close, SP, Elliott, DJ, Hayes, AG, et al. Effects of classical and novel agents in an MPTP-induced reversible model of Parkinson’s disease. Psychopharmacology 1990; 102(3): 195300.CrossRefGoogle Scholar
18.Marsden, CD, Coleman, RJ, Quinn, NP, et al. Nasogastric and intravenous infusions of PHNO in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1990; 53(2): 102105.Google Scholar
19.Olanow, CW, Werner, EG, Gauger, LL.CV 205–502: Safety, tolerance to and efficacy of increasing doses in patients with Parkinson’s disease in a double-blind placebo cross-over study. Clin Neuropharmacol 1989; 12(6): 490497.CrossRefGoogle Scholar
20.Temlett, JA, Quinn, NP, Jenner, PG, et al. Antiparkinsonian activity of CY 208–243, a partial D-l dopamine receptor agonist, in MPTP-treated marmosets and patients with Parkinson’s disease. Mov Disord 1989; 4: 261265.CrossRefGoogle Scholar
21.Pfeiffer, RF, Herrera, LH, Glaeske, CS, et al. CQP 201–403 in Parkinson’s disease: an open-label pilot study. Mov Disord 1989; 4: 278281.CrossRefGoogle ScholarPubMed