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D-1 and D-2 Agonists in Parkinson's Disease

Published online by Cambridge University Press:  05 January 2016

Abraham N. Lieberman ,
Menek Goldstein ,
Govindan Gopinathan  and
Andreas Neophytides
Abraham N. Lieberman*
Affiliation:
New York University School of Medicine and New York Infirmary - Beekman Downtown Medical Center, New York
Menek Goldstein
Affiliation:
New York University School of Medicine and New York Infirmary - Beekman Downtown Medical Center, New York
Govindan Gopinathan
Affiliation:
New York University School of Medicine and New York Infirmary - Beekman Downtown Medical Center, New York
Andreas Neophytides
Affiliation:
New York University School of Medicine and New York Infirmary - Beekman Downtown Medical Center, New York
*
650 First Avenue, New York, New York, U.S.A. 10016
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Abstract:

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We have evaluated 5 DA agonists-bromocriptine, lergotrile, lisuride, pergolide, and mesulergine in studies encompassing 278 patients with advanced PD. In most of our patients the DA agonist was added to levodopa. Most of our patients were no longer satisfactorily responding to levodopa. Previous attempts at managing these patients by changing the dose of levodopa (increasing or decreasing it), the treatment schedule, or the ratio of levodopa to carbidopa or by temporarily discontinuing levodopa [drug holiday] were unsuccessful. The majority of our patients had diurnal fluctuations in performance, either “wearing off” or “on-off” phenomena. The addition of a DA agonist resulted in a decrease in parkinsonian disability in most patients and a decrease in the severity of the diurnal fluctuations in performance. Improvement in many patients was maintained for at least 2 years. Adverse effects included mental changes, dyskinesias, orthostatic hypotension, and nausea. All of the adverse effects were reversible when the agonist was decreased or discontinued. As a group the agonists behaved similarly but individual patients often responded better to one agonist than another. The main role of agonists is in combination with levodopa in the treatment of patients with early PD who have not yet developed dyskinesias or diurnal fluctuations in performance.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 14 , Issue S3 , August 1987 , pp. 466 - 473
Copyright
Copyright © Canadian Neurological Sciences Federation 1987

References

REFERENCES

1.Marsden, CD, Parkes, JD.Success and problems of long-term levodopa therapy in Parkinson’s disease. Lancet 1977; 1: 345–349.CrossRefGoogle ScholarPubMed
2.Bemheimer, J, Birkmayer, W.Hornykiewicz, O.Brain Dopamine in syndromes of Parkinson and Huntington. J Neurol Sci 1973; 20: 415–455.CrossRefGoogle Scholar
3.Ungerstedt, U.Post-synaptic supersensitivity after 6-hyrdoxy-dopamine induced degeneration of the nigrostriatal dopamine system. Acta Physiol Scand 1971 ; 367(Suppl): 69–93.CrossRefGoogle Scholar
4.Agid, Y, Javoy, F, Glowinski, J.Hyperactivity of the remaining neurones after partial destruction of the nigrostriatal dopaminergic system in the rat. Nature 1973; 245: 150–151.Google ScholarPubMed
5.Melamed, E, Hefti, F, Wurtman, RJ.Diminished decarboxylation of L-dopa in rat striatum after intrastriatal injections of kainic acid. Neuropharmacology 1980; 19: 409–411.CrossRefGoogle ScholarPubMed
6.Marsden, CD, Parkes, JD, Quinn, N.Fluctuations of disability in Parkinson's disease - clinical aspects, in Marsden, CD, Fahn, S (eds.) Movement Disorders. London, Butterworth, 1982, pp 106–128.Google Scholar
7.Muenter, MD.Sharpless, NS.Tyce, GM.Patterns of Dystonia (“1.D.I” and “D.I.D”) in response to L-dopa therapy for Parkinson's disease. Mayo Clinic Proc 1977; 52: 165–174.Google Scholar
8.DeJong, GJ, Meerwaldt, JD.Response variations in the treatment of Parkinson’s disease. Neurology 1984:34: 1507–1509.CrossRefGoogle Scholar
9.Spencer, SE, Wooten, GF., Altered Pharmacokinetics of L-dopa metabolism in rat striatum deprived of dopaminergic innervation. Neurology 1984; 34: 1105–1108.CrossRefGoogle ScholarPubMed
10.Quinn, N.Parkes, JD, Marsden, CD.Control of on/off phenomenon by continuous intravenous infusion of levodopa. Neurology 1984; 34: 1131–1136.CrossRefGoogle Scholar
11.Lieberman, AN, Goldstein, M, Gopinathan, G.Combined use of benserazide and carbidopa in Parkinson’s disease. Neurology 1984; 34: 227–229.Google ScholarPubMed
12.Nutt, JG, Woodward, WR, Hammerstad, JP, et al. The “on-off” phenomenon in Parkinson's disease. Relation to levodopa absorption and transport. New Eng J Med 1984; 310: 483–488.CrossRefGoogle Scholar
13.Nutt, JG, Woodward, WR.Levodopa pharmacokinetics and pharmoacodynamics in fluctuating parkinsonian patients. Neurology 1986; 36: 739–744.CrossRefGoogle Scholar
14.Dougan, D, Wade, D, Mearrick, P.Effects of L-dopa metabolites at a dopamine receptor suggest a basis for “on-off” effect in Parkinson’s disease. Nature 1975; 254: 70–72.CrossRefGoogle Scholar
15.Lesser, RP, Fahn, S, Snider, SP, et al. Analysis of the clinical problems in parkinsonism and the complications of long-term levodopa therapy. Neurology 1979; 29: 1253–1260.CrossRefGoogle ScholarPubMed
16.Direnfeld, LK, Feldman, RC, Alexander, MP.Is L-dopa drug holi-day useful. Neurology 1980; 30: 785–788.CrossRefGoogle ScholarPubMed
17.Rinne, UK.Combined bromocriptine-levodopa therapy early in Parkinson’s disease. Neurology 1985; 35: 1196–1198.CrossRefGoogle ScholarPubMed
18.Kebabian, JW, Petzold, GL, Greengard, P.Dopamine sensitive ade- nylate cyclase in caudate nucleus of rat brain and its similarity to the dopamine receptor. Proc Natl Acad Sci USA 1972; 69: 2145–2149.CrossRefGoogle Scholar
19.Schwarcz, R, Fuxe, K, Agnati LF. Effects 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: 465–470.CrossRefGoogle Scholar
20.Schwarcz, R, Creese, I, Coyle, JT.Dopamine receptors localized on cerebral cortical afferents to rat striatum. Nature 1978; 271: 766–768.CrossRefGoogle Scholar
21.Trugman, JM, Geary, WA, Wooten, GF.Localization of D2 dopa-mine receptors to intrinsic striatal neurons by quantitative autoradiography. Nature 1986; 323: 267–269.CrossRefGoogle Scholar
22.Rabey, JM, Passeltiner, P, Markey, K.Stimulation of pre and post- synaptic dopamine receptors by an ergoline and by a partial ergoline. Brain Research 1981; 225: 347–356.CrossRefGoogle Scholar
23.Goldstein, M, Lew, JY, Engel, J.Dopaminephillic properties of ergot derivatives. In: Fuxe, K, Calne, DB, eds.Dopaminergic ergot derivatives and motor function. Oxford: Pergamon Press, 1979: 253–260.CrossRefGoogle Scholar
24.Reisine, TD, Fields, JZ, Yamamura, HJ.Neurotransmitter receptor alterations in Parkinson’s disease. Life Sci 1977; 21: 335–344.CrossRefGoogle ScholarPubMed
25.Rinne, UK, Koskinen, V, Lonnberg, P.Neurotransmitter receptors in the parkinsonian brain. Parkinson Disease edited by Rinne UK, Klinger, M, and Stamm, G.Elsevier North Holland BioMedical Press 1980; 93–107.Google Scholar
26.Goldstein, M, Lieberman, AN, Lew, JY. Interaction of pergolide with central dopaminergic receptors. Proc Natl Acad Sci 1980; 77: 3725–3728.CrossRefGoogle ScholarPubMed
27.Lew, JY, Meller, E, Goldstein, M.Photoaffinity labeling and purifica- tion of solubilized D2 dopamine receptors. EuropJ Pharm 1985; 113: 145–146.CrossRefGoogle Scholar
28.Lew, JY, Goldstein, M.Solubilization and characterization of striatal dopamine receptors. J Neurochem 1984; 42: 1298–1305.CrossRefGoogle ScholarPubMed
29.Lieberman, A, Goldstein, M.Bromocriptine in Parkinson Disease. Pharm Reviews 1985; 37: 217–227.Google ScholarPubMed
30.Goldstein, M, Lieberman, A, Meller, E.A possible molecular mecha- nism for the anti-parkinsonian action of bromocriptine in combination with levodopa. Trends in Pharm Sci 1985; 6: 436–437.CrossRefGoogle Scholar
31.Meller, E, Hellmer, , Matyjek, E, et al. Receptor reserve at striatal dopamine autoreceptors: Implications for selectivity of dopamine agonists. EuropJ of Pharmacology 1986; 123: 311–314.Google Scholar
32.Trugman, JM, Wooten, GF.The effects of L-dopa on regional cerebral glucose utilization in rats with unilateral lesions of the substantia nigra. Brain Research 1986; 379: 264–274.CrossRefGoogle ScholarPubMed
33.Bennett, JP, Wooten, GF.Dopamine Denervation does not alter in vivo3H spiperone binding in rat striatum: Implications for external imaging of dopamine receptors in Parkinson’s disease. Ann Neurol 1986; 19: 378–383.CrossRefGoogle ScholarPubMed
34.Herrera, , Marschitz, M, Ungerstedt, U.Evidence that striatal effer- ents relate to different dopamine receptors. Brain Research 1984; 323: 269–278.CrossRefGoogle Scholar
35.Herrera, , Marschitz, M, Ungerstedt, U.Evidence that apomorphine and pergolide induce rotation in rats by different actions on D1, and D2 receptor sites. Europ J of Pharm 1984; 98: 165–176.CrossRefGoogle Scholar
36.Calne, DB, Williams, AC, Neophytides, A.Long-term treatment of parkinsonism with bromocriptine. Lancet 1978; 1: 735–738.CrossRefGoogle ScholarPubMed
37.Lieberman, A, Kupersmith, M, Estey, E.The treatment of Parkinson’s disease with bromocriptine. New Engl J Med 1976; 295: 1400–1404.CrossRefGoogle ScholarPubMed
38.Lieberman, A, Kupersmith, M, Gopinathan, G.Bromocriptine in Parkinson’s disease: Further studies. Neurology 1979; 29:363–369.CrossRefGoogle ScholarPubMed
39.Lieberman, AN, Dziatelowski, M, Kupersmith, M.The evaluationof Parkinson’s disease. Adv Biochem Psychopharmacol 1980; 23: 277–286.Google Scholar
40.Lieberman, A, Kupersmith, M, Neophytides, A.Long-term efficacy of bromocriptine in Parkinson's disease. Neurology 1980; 30: 518–523.CrossRefGoogle Scholar
41.Lieberman, A, Miyamoto, T, Battista, A, et al. Studies on the antiparkinsonian efficacy of lergotrile. Neurology 1975; 25:459–462.CrossRefGoogle ScholarPubMed
42.Lieberman, AN, Gopinathan, G, Estey, E.Lergotrile in Parkinson’s disease: Further studies. Neurology 1979; 29: 267–272.CrossRefGoogle ScholarPubMed
43.Lieberman, AN, Kupersmith, M, Gopinathan, G.Modification of the “on-off” effect by bromocriptine and lergotrile. In: Fuxe, K, Calne, DB, eds. Dopaminergic ergot derivatives and motor function. Oxford: Pergamon Press, 1979: 285–295.CrossRefGoogle Scholar
44.Lieberman, A, Goldstein, M, Neophytides, A.Lisuride in Parkinson’s disease: The efficacy of lisuride compared to levodopa. Neurology 1981; 31: 961–965.CrossRefGoogle ScholarPubMed
45.Lieberman, A, Goldstein, M, Gopinathan, G.Further studies with lisuride in Parkinson’s disease. Eur Neurol 1983; 22: 119–123.Google Scholar
46.Lieberman, A, Gopinathan, G, Neophytides, A.Bromocriptine and lisuride in Parkinson’s disease. Ann Neurol 1983; 13: 44–77.CrossRefGoogle Scholar
47.Lemberger, L, Crabtree, RE.Pharmacological effects in man of a potent long-acting dopamine receptor agonist. Science 1979; 205: 1151–1153.Google Scholar
48.Lieberman, A.Goldstein, M, Leibowitz, M.Treatment of advanced Parkinson’s disease with pergolide. Neurology 1981:31:675–682.CrossRefGoogle ScholarPubMed
49.Lieberman, AN, Goldstein, M, Gopinathan, G.Further studies with pergolide in Parkinson’s disease. Neurology 1982:32: 1181–1184.CrossRefGoogle ScholarPubMed
50.Lieberman, AN, Goldstein, M.Leibowitz, M.Long-term treatment with pergolide: Decreased efficacy with time. Neurology 1984: 34: 223–226.Google ScholarPubMed
51.Lieberman, AN, Neophytides, A, Leibowitz, M.Comparative effi- cacy of pergolide and bromocriptine in patients with advanced Parkinson’s disease. Adv Neurol 1983: 37: 95–108.Google Scholar
52.Lewitt, PA, Ward, MD, Larsen, TA. Comparison of pergolide and bromocriptine therapy in parkinsonism. Neurology 1983: 33: 1009–1014.Google Scholar
53.Lieberman, AN.Gopinathan, G, Neophytides A. Pergolide and lisuride in advanced Parkinson's disease. Adv Neurol 1983: 40: 503–507.Google Scholar
54.Gopinathan, G, Lieberman, AN, Pasternack, D.Mesulergine in Parkinson’s disease. Canad J Neurol Sci (submitted).Google Scholar
55.Hökfelt, T, Holets, VRStaines, W.Coexistence of neuronal messen- gers - An overview. Prog in Brain Research 1986: 68: 33–70.CrossRefGoogle Scholar