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Stimulation of a dopamine-sensitive adenylate cyclase in homogenates of rat striatum by a metabolite of piribedil (ET 495)

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Summary

The addition of dopamine (1–100μM) to homogenates of rat striatum incubated with ATP evoked a 120% increase in the rate of cyclic 3′5′ adenosine monophosphate (cyclic AMP) production. The effects of added dopamine were mimicked by the addition of the compound S 584 [1-3,4-(dihydroxybenzyl)-4-(2-pyrimidinyl) piperazine] (1–100 μM), a catechol metabolite of the dopaminergic stimulant drug piribedil (ET 495). The latter substance was itself inactive in this system at these concentrations. The stimulation of cyclic AMP production by dopamine and by S 584 was potently inhibited by the dopamine antagonist dru chlorpromazine and spiroperidol (1–10 μM). It is possible that the dopaminergic effects elicited by piribedil may be mediated through the active metabolite S 584.

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References

  • Brown, B. L., Ekins, R. D., Albano, J. D. M.: In: Advances in cyclic nucleotide research, Vol. II, pp. 25–40, P. Greengard and G. A. Robison, Ed. New York: Raven Press 1972

    Google Scholar 

  • Brown, J. H., Makman, M. H.: Stimulation of adenylate cylcase in retinal homogenates and of cyclic AMP production in intact retina. Proc. Acad. Sci. (Wash.) 69, 539–543 (1972)

    Google Scholar 

  • Campbell, D. B., Jenner, P., Taylor, A. R.: Metabolism and kinetics of ET 495 (piribedil) in man and rats. Advanc. Neurol. 3, 199–213 (1973)

    Google Scholar 

  • Corrodi, H., Fuxe, K., Ungerstedt, Z.: Evidence for a new type of dopamine receptor stimulating agent. J. Pharm. Pharmacol. 23, 989–991 (1971)

    Google Scholar 

  • Costall, B., Naylor, R. J.: The site and mode of action of ET 495 for the mediation of stereotyped behaviour in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 117–133 (1973)

    Google Scholar 

  • Fuxe, K.: Tools in the treatment of Parkinson's disease: studies of new types of dopamine receptor stimulating agents. Advanc. Neurol. 3, 273–279 (1973)

    Google Scholar 

  • Goldstein, M., Angnoste, B., Shirran, C.: The effect of trivastal, haloperidol and dibutyryl cyclic AMP on 14C-dopamine synthesis in rat striatum. J. Pharm. Pharmacol. 25, 348–351 (1973)

    Google Scholar 

  • Jenner, P., Taylor, A. R., Campbell, D. B.: Preliminary investigation of the metabolism of piribedil (ET 495); a new central dopaminergic agonist and potential anti-Parkinson agent. J. Pharm. Pharmacol. 25, 749–750 (1973)

    Google Scholar 

  • Kebabian, J. W., Petzold, G. L., Greengard, P.: Dopamine sensitive adenylate cyclase in the caudate of rat brain and its similarity to the “dopamine receptor”. Proc. nat. Acad. Sci. (Wash.) 69, 2145–2149 (1972)

    Google Scholar 

  • Poignant, J. M., Laubie, M., Tscouris-Kupfer, D., Schmitt, H.: Action de divers reactif pharmacologiques sur les movements stereotypes produits chez le rat par l'ingestion de 1-(2-pyrimidyl)-4-piperonyl piperazine (Piribedil). C. R. Acad. Sci. (Paris) 275, 715–717 (1972)

    Google Scholar 

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Miller, R.J., Iversen, L.L. Stimulation of a dopamine-sensitive adenylate cyclase in homogenates of rat striatum by a metabolite of piribedil (ET 495). Naunyn-Schmiedeberg's Arch. Pharmacol. 282, 213–216 (1974). https://doi.org/10.1007/BF00499035

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  • DOI: https://doi.org/10.1007/BF00499035

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