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Therapeutic Potentials of Centrally Acting Dopamine and α2-Adrenoreceptor Agonists

  • M. Goldstein
  • J. Engel
  • A. Lieberman
  • I. Regev
  • A. Bystritsky
  • S. Mino
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 18)

Summary

The antiparkinsonian activity of several dopamine agonists was investigated in an animal model and clinically in parkinsonian patients. The semisynthetic ergoline, pergolide, the partial ergoline, LY 141865 and the 8-α-aminoergoline, CU 32-085 were found to be effective antitremor agents in monkeys with ventromedial tegmental lesions. The administration of pergolide or LY 141865 results in a relief of tremor with a concomitant occurrence of severe abnormal involuntary movements, while the administration of CU 32-085 results in a relief of tremor with the occurrence of only minor abnormal involuntary movements. Clinical studies have revealed that pergolide is an effective drug in patients with advanced Parkinson’s disease, and it reduces the “on-off” phenomena. The possible regulation of dopamine neurotransmission by the norepinephrine neuronal systems was reviewed. Preliminary data suggest that clonidine may interact with presynaptic dopamine receptors.

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References

  1. Antelman, S. M., Caggiula, A. R.: Norepinephrine-dopamine interactions and behavior. Science 195, 646–653 (1977).CrossRefPubMedGoogle Scholar
  2. Di Paolo, T., Poyet, P., Labrie, F.: Effect of chronic estradiol and haloperidol treatment on striatal dopamine receptors. Eur. J. Pharmacology 73, 105–106 (1981).CrossRefGoogle Scholar
  3. Engel, J. A., Johannessen, K., Liljequist, S., Goldstein, M.: Enhancement of the haloperidol-induced suppression of food-reinforced lever-pressing behavior by interaction with a2-adrenoreceptors. Abstract, Society for Neuroscience, Minneapolis, Minn., 1982.Google Scholar
  4. Enz, A.: Biphasic influence of a Sa-amino ergoline, CU 32–085, on striatal dopamine synthesis and turnover in vivo in the rat. Life Sci. 29, 2227–2234 (1981).CrossRefPubMedGoogle Scholar
  5. Fields, J.Z., Gordon, J. H.: Estrogen inhibits the dopaminergic supersensitiv- ity induced by neuroleptics. Life Sciences 30, 229–234 (1982).CrossRefPubMedGoogle Scholar
  6. Freedman, R., Kirch, D., Bell, J Adler, L. E., Pecevich, M., Pachtman, E., Denver, P.: Clonidine treatment of schizophrenia: Double-blind comparison to placebo and neuroleptic drugs. Acta psychiat. scand. 65, 35–45 (1982).CrossRefPubMedGoogle Scholar
  7. Fuxe, K., Fredholm, B. B., Ogren, S.-O., Agnati, L. F., Hökfelt, T, Gustafsson, J. A.: Ergot drugs and central monoaminergic mechanisms: A histochemical, biochemical and behavioral analysis. Fed. Proc. 37, 2181–2191 (1978).Google Scholar
  8. Glaeser, B. S., Berry, J. C., Boyar, W. C., Lovell, R.A.: Effect of acute clonidine administration on striatal dopamine autoreceptors. Abstract, Society for Neuroscience, Minneapolis, Minn., 1982.Google Scholar
  9. Goldstein, M., Battista, A. F., Ohmoto, T., Anagnoste, B., Fuxe, K.: Tremor and involuntary movements in monkeys: Effects of L-dopa and of a dopamine receptor stimulating agent. Science 179, 816 (1973).CrossRefPubMedGoogle Scholar
  10. Goldstein, M., Lew, J. Y., Nakamura, S., Battista, A., Lieberman, A., Fuxe, K.: Dopaminophilic properties of ergot alkaloids. Fed. Proc. 37, 2202–2206 (1978).PubMedGoogle Scholar
  11. Goldstein, M., Lew,J. Y., Sauter, A., Lieberman, A.: The affinities of ergot compounds for dopamine and dopamine antagonist receptor sites. In: Ergot Compounds and Brain Function: Neuroendocrine and Neuropsychiatric Aspects, pp. 75–82. New York: Raven Press. 1980.Google Scholar
  12. Goldstein, M., Lieberman, A., Lew, J. Y., Asano, T, Rosenfeld, M., Makman, M. H.: Interaction of pergolide with central dopaminergic receptors. Proc. nat. Acad. Sci. (U.S.A.) 6, 3725–3728 (1980).CrossRefGoogle Scholar
  13. Jellinger, K.: Adjuvant treatment of Parkinson’s disease with dopamine agonists: Open trial with bromocriptine and CU 32–085. J. Neurol. 227, 75–88 (1982).CrossRefPubMedGoogle Scholar
  14. Kostowski, W., Jerlicz, M., Bidzinski, A., Hauptmann, M.: Evidence for existence of two opposite noradrenergic brain systems controlling behavior. Psychopharmacology 59, 311–312 (1978).CrossRefPubMedGoogle Scholar
  15. Poirier, L.J., Sourkes, T. L.: Influence of the substantia nigra on the catecholamine content of the striatum. Brain 88, 181–189 (1965).CrossRefPubMedGoogle Scholar
  16. Rabey, J. M., Passeltiner, P., Markey, K., Asano, T, Goldstein, M.: Stimulation of pre- and postsynaptic dopamine receptors by an ergoline and by a partial ergoline. Brain Res. 225, 347–356 (1981).CrossRefPubMedGoogle Scholar
  17. Rabey, J M., Passeltiner, P., Bystritsky, A., Engel, J., Goldstein, M.: The regulation of striatal DOPA synthesis by r2-adrenoreceptors. Brain Research 230, 422–426 (1981 a).Google Scholar
  18. Ringwald, E., Hirt, D., Markstein, R., Vigouret, J. M.: Dopamine Rezeptoren-Stimulation in der Behandlung der Parkinson-Krankheit. Nervenarzt 53, 67–71 (1982).PubMedGoogle Scholar
  19. Sailer, C.F., Chiodo, L.A.: Glucose suppresses basal firing and haloperidol-induced increases in the firing rate of central dopaminergic neurons. Science 210, 1269–1271 (1980).CrossRefGoogle Scholar
  20. Sailer, C.F., Kopin, I.J.: Glucose potentiates haloperidol-induced catalepsy. Life Sci. 29, 2337–2341 (1981).CrossRefGoogle Scholar
  21. Ungerstedt, U.: Stereotaxic mapping of the monoamine pathways in the rat brain. Acta physiol. Scand. Suppl. 367, 1–48 (1971).Google Scholar
  22. Walters,J. R., Roth, R. H.: Dopaminergic neurons: An in-vivo system for measuring drug interactions with presynaptic receptors. Naunyn-Schmiedeberg’s Arch. Pharmacol. 26, 5–12 (1976).Google Scholar

Copyright information

© Springer-Verlag Wien 1983

Authors and Affiliations

  • M. Goldstein
    • 4
  • J. Engel
    • 2
  • A. Lieberman
    • 3
  • I. Regev
    • 1
  • A. Bystritsky
    • 1
  • S. Mino
    • 1
  1. 1.Departments of PsychiatryNew York University Medical CenterNew YorkUSA
  2. 2.Departments of NeurologyNew York University Medical CenterNew YorkUSA
  3. 3.Department of PharmacologyUniversity of GöteborgGöteborgSweden
  4. 4.Departments of PsychiatryNew York University Medical CenterNew YorkUSA

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