Summary
Ergot derivatives such as bromocriptine, lergotrile, pergolide, and mesulergine relieve tremor and elicit abnormal involuntary movements in monkeys with ventromedial tegmental lesions. These ergots are of therapeutic value in patients with advanced Parkinson’s disease, especially in those whose condition is complicated by diurnal oscillations in performance and/or who no longer respond to treatment with levodopa alone. Some nonergot dopamine agonists (e.g., LY 141865, EMD 23–448, AY 27–110) stimulate, at low doses, presynaptic, as well as supersensitive postsynaptic, dopamine receptors. Results obtained from studies in animal models suggest that these compounds might be effective antiparkinsonian agents.
In separate study, we have investigated the properties of solubilized striatal D-2 dopamine receptors. Evidence has been obtained that the D-2 dopamine receptor is a glycoprotein, and that the ganglioside, GM-1, interacts with the lectin, WGA, at a similar site as the dopamine receptor.
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References
Agnati, L.F., Fuxe, K., Calza, L., Benfenati, F., Cavicchioli, L., Toffano, G., and Goldstein, M.: Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting. Acta Physiol Scand. (1983), 119: 347–363, 1983.
Ahmed, F.R., and Bagli, J.: Troponoid. V. Crystallographic studies on AY-27110—a dopamine agonist of the troponylpiperazine series. Can. J. Chem. 60, 2687–2691 (1982).
Calne, D.B., Teychenne, P.F., Calveria, L.E., etal.: Bromocriptine in Parkin-sonism. Br. Med. J. 4, 442–444 (1974).
Corrodi, H., Fuxe, K., Hokfelt, T., Lidbrink, P., and Ungerstedt, U.: Effect of ergot drugs on central catecholamine neurons: Evidence for a stimulation of central dopamine neurons. J. Pharm. Pharmacol. 25, 409–411 (1973).
Enz, A.: Biphasic influence of a 8α-amino ergoline, CU 32-085, on striatal dopamine synthesis and turnover in vivo in the rat. Life Sci. 29, 2221–223A (1981).
Fuxe, K., Corrodi, H., Hokfelt, T., Lidbrink, P., and Ungerstedt, U.: Ergocornine and 2-Br-a-ergocryptine. Evidence for prolonged dopamine recept6or stimu-lation. Med. Bio. 52, 121 (1974).
Goldstein, M., Battista, A.F., Nakatani, S., and Anagnoste, B.: The effects of centrally acting drugs on tremor in monkeys with mesencephalic lesions. Proc. Natl. Acad. Sci. USA 63, 1113 (1969).
Goldstein, M., Lew, J.Y., Nakamura, S., Battista, A.F., Lieberman, A., and Fuxe, K.: Dopaminephilic properties of ergot alkaloids. Fed. Proc. 37, 78–82 (1978).
Goldstein, M., Lew, J.Y., Engel, J., etal.: The dopaminephillic properties of ergoline derivatives. In Fuxe, K., and Calne, D.B. (Eds.), Dopaminergic Ergot Derivatives and Motor Function, pp. 253–260. Oxford: Pergamon, 1979.
Goldstein, M., Engel, J., Lieberman, A., Regev, I., Bystritsky, A., and Mino, S.: Therapeutic potentials of centrally acting dopamine and α2-adrenoreceptor agonists. J. Neural Transmission, Suppl. 18, 257–263 (1983a).
Goldstein, M., Lew, J., Bystritsky, A., Lieberman, A., Engel, J., and Liljequist, S.: Multiple dopamine receptors: Interaction with a2-adrenoreceptors. In Agnoli, A., Crepaldi, G., Spano, P.F. and Trabucchi, M., Aging Brain and Ergot Alkaloids, pp. 241–247. Aging, Vol. 23. New York: Raven, 1983.
Lemberger, L., Crabtree, R., Clemens, J., etal.: The inhibitory effect of an ergoline derivative (Lergotrile, Compound 83636) on prolactin secretion in man. J. Clin. Endocrinol. Metab. 39, 579–584 (1974).
Lew, J.Y., and Goldstein, M.: Dopamine receptor binding for agonists and antagonists in thermal exposed membranes. Eur. J. Pharmacol. 55, 429–430 (1979).
Lew, J.Y., Fong, J.C., and Goldstein, M.: Solubilization of the neuroleptic binding receptor from rat striatum. Eur. J. Pharmacology 72, 403–405 (1981).
Lew, J.Y., and Goldstein, M.: The solubilization and characterization of striatal dopamine receptors. J. Neurochem. 42: 1298–1305 (1984).
Lieberman, A., Miyamoto, T., Battista, A.F., and Goldstein, N.: Studies on the antiparkinsonian efficacy of lergotrile. Neurology 25, 459–462 (1975).
Lieberman, A., Kupersmith, M., Estey, E., and Goldstein, M.: Treatment of Parkinson’s disease with bromocriptine. New Eng. J. Med. 295, 1400–1404 (1976).
Lieberman, A., Goldstein, M., Leibowitz, M., Neophytides, A., Kupersmith, M., Pact, V., and Kleinberg, D.: Treatment of advanced Parkinson disease with pergolide. Neurology 31, 675–681 (1981).
Lieberman, A., Goldstein, M., Gopinthan, G., Leibowitz, M., Neophytides, A.,
Walker, R., Hiesiger, E., and Nelson, J.: Further studies with pergolide in Parkinson disease. Neurology 32, 1181–1184 (1982).
Miyamoto, T., Battista, A., Goldstein, M., and Fuxe, K.: Long-lasting antitremor activity induced by 2-Br-a-ergocryptine in monkeys. J. Pharm. Pharmacol. 26, 452 (1974).
Poirier, L.J., and Sourkes, T.L.: Influence of the substantia nigra on the catecholamine content of the striatum. Brain 88, 181 (1965).
Rabey, M.J., Passeltiner, P., Markey, K., Asano, T., and Goldstein, M.: Stimulation of pre- and postsynaptic dopamine receptors by an ergoline and by a partial ergoline. Brain Res. 225, 347–356 (1981).
Schwarcz, R., Creese, I., Coyle, J.T., and Snyder, S.H.: Dopamine receptors localized on cerebral cortical afferents to rat corpus striatum. Nature(Lond.) 271, 766–768 (1978).
Seyfried, C.A., Fuxe, K., Wolf, H.-P., and Agnati, L.F.: Demonstration of a new type of dopamine receptor agonist: an indolyl-3-butylamine. Actions at intact versus supersensitive dopamine receptors in the rat forebrain. Acta Physiol. Scand. 116, 465–468 (1982).
Yoshino, K., Matyjek, E.H., and Goldstein, M.: The effect of the indol-alkyl-piperdine derivative EMD 23-448 on pre- and postsynaptic central dopamine receptors. Abstract #538, Fed.Proc. 42, 384 (1983).
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Goldstein, M., Lew, J.Y., Lieberman, A., Fuxe, K. (1985). Dopamine Receptors: Antiparkinsonian Activity and Molecular Mechanisms. In: Gaitz, C.M., Samorajski, T. (eds) Aging 2000: Our Health Care Destiny. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-5058-6_12
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DOI: https://doi.org/10.1007/978-1-4612-5058-6_12
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