Dopamine Receptors: Antiparkinsonian Activity and Molecular Mechanisms

  • Menek Goldstein
  • Jow Y. Lew
  • Abraham Lieberman
  • Kjell Fuxe
Conference paper

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.

Keywords

Dopamine Catecholamine Levodopa Parkin Dopa 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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.Google Scholar
  2. 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).CrossRefGoogle Scholar
  3. Calne, D.B., Teychenne, P.F., Calveria, L.E., etal.: Bromocriptine in Parkin-sonism. Br. Med. J. 4, 442–444 (1974).PubMedCrossRefGoogle Scholar
  4. 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).PubMedCrossRefGoogle Scholar
  5. 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).Google Scholar
  6. 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).Google Scholar
  7. 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).PubMedCrossRefGoogle Scholar
  8. 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).Google Scholar
  9. 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.Google Scholar
  10. 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).Google Scholar
  11. 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.Google Scholar
  12. 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).PubMedCrossRefGoogle Scholar
  13. Lew, J.Y., and Goldstein, M.: Dopamine receptor binding for agonists and antagonists in thermal exposed membranes. Eur. J. Pharmacol. 55, 429–430 (1979).PubMedCrossRefGoogle Scholar
  14. 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).CrossRefGoogle Scholar
  15. Lew, J.Y., and Goldstein, M.: The solubilization and characterization of striatal dopamine receptors. J. Neurochem. 42: 1298–1305 (1984).PubMedCrossRefGoogle Scholar
  16. Lieberman, A., Miyamoto, T., Battista, A.F., and Goldstein, N.: Studies on the antiparkinsonian efficacy of lergotrile. Neurology 25, 459–462 (1975).PubMedGoogle Scholar
  17. Lieberman, A., Kupersmith, M., Estey, E., and Goldstein, M.: Treatment of Parkinson’s disease with bromocriptine. New Eng. J. Med. 295, 1400–1404 (1976).PubMedCrossRefGoogle Scholar
  18. 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).PubMedGoogle Scholar
  19. Lieberman, A., Goldstein, M., Gopinthan, G., Leibowitz, M., Neophytides, A.,Google Scholar
  20. Walker, R., Hiesiger, E., and Nelson, J.: Further studies with pergolide in Parkinson disease. Neurology 32, 1181–1184 (1982).PubMedGoogle Scholar
  21. 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).PubMedCrossRefGoogle Scholar
  22. Poirier, L.J., and Sourkes, T.L.: Influence of the substantia nigra on the catecholamine content of the striatum. Brain 88, 181 (1965).PubMedCrossRefGoogle Scholar
  23. 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).PubMedCrossRefGoogle Scholar
  24. 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).Google Scholar
  25. 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).PubMedCrossRefGoogle Scholar
  26. 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).Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1985

Authors and Affiliations

  • Menek Goldstein
  • Jow Y. Lew
  • Abraham Lieberman
  • Kjell Fuxe

There are no affiliations available

Personalised recommendations