PRE-SYNAPTIC AND POSTSYNAPTIC ALPHA ADRENOCEPTOR SELECTIVITY STUDIES WITH YOHIMBINE AND ITS 2 DIASTEREOISOMERS RAUWOLSCINE AND CORYNANTHINE IN THE ANESTHETIZED DOG

  • 1 January 1981
    • journal article
    • research article
    • Vol. 219  (2) , 540-546
Abstract
The selectivity of yohimbine and its 2 diastereoisomers rauwolscine and corynanthine for pre- and postsynaptic .alpha. adrenoceptors was investigated in the anesthetized dog. Antagonism of the inhibitory effect of clonidine on the tachycardia produced by electrical stimulation of the ansa subclavia was used as a measure of presynaptic .alpha.-2 adrenoceptor blockade. Inhibition of the diastolic pressor response to phenylephrine in ganglion and .beta. blocked dogs was used as a measure of postsynaptic .alpha.-1 adrenoceptor blockade. All 3 of the isomers reduced, and at higher doses reversed, the inhibitory effect of clonidine. Yohimbine and rauwolscine were equipotent in this respect and were approximately 100-fold more potent than corynanthine. All the isomers were equipotent as antagonists of the diastolic pressor response to phenylephrine. Yohimbine and rauwolscine were approximately 30 .times. more potent as .alpha.-2 adrenoceptor than .alpha.-1 adrenoceptor antagonists, whereas corynanthine was 10-fold more potent at .alpha.-1 adrenoceptors than at .alpha.-2 adrenoceptors. These results are in agreement with those previously reported from in vitro experiments showing yohimbine and rauwolscine to be preferential .alpha.-2 adrenoceptor antagonists and corynanthine to be a preferential .alpha.-1 adrenoceptor antagonist. The high affinity of the antagonists yohimbine and rauwolscine for .alpha.-2 adrenoceptors probably is responsible for their selectivity because at the level of blockade of postsynaptic .alpha.-1 adrenoceptors both isomers were equipotent with corynanthine.