Characterization of alpha-adrenoceptors participating in the central hypotensive and sedative effects of clonidine using yohimbine, rauwolscine and corynanthine

European Journal of Pharmacology
P B TimmermansP A Van Zwieten

Abstract

The central alpha-adrenoceptors responsible for mediating the clonidine-induced central hypotension in anaesthetized cats and sedation in mice have been characterized according to their sensitivities to the alpha-adrenoceptor antagonist yohimbine and its two diastereomeric congeners rauwolscine and corynanthine. Yohimbine and rauwolscine (1-10 microgram/kg) dose-dependently antagonized the central hypotensive response to clonidine (1 microgram/kg) applied 15 min later. Greater amounts of corynanthine (30-100 micrograms/kg) had to be administered to diminish the central depressor effect of clonidine. In these studies the drugs were infused via the left vertebral artery. The prolongation of the hexobarbitone-induced loss of the righting reflex in mice by clonidine (0.3 mg/kg, i.p.) was inhibited by previous treatment with yohimbine and rauwolscine (0.04-5 mg/kg, i.p.) in a dose-dependent manner, but not by corynanthine. Binding experiments with rat isolated cerebral membranes demonstrated the higher affinity of yohimbine and rauwolscine for the [3H] clonidine- than for the [3H]prazosin-specific binding sites. The reverse was found for corynanthine. The relative potencies of yohimbine, rauwolscine and corynanthine in inhibiting th...Continue Reading

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Citations

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