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Abstract

Pre- and postsynaptic alpha adrenoceptor selectivity studies with yohimbine and its two diastereoisomers rauwolscine and corynanthine in the anesthetized dog.

N B Shepperson, N Duval, R Massingham and S Z Langer
Journal of Pharmacology and Experimental Therapeutics November 1981, 219 (2) 540-546;
N B Shepperson
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N Duval
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R Massingham
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S Z Langer
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Abstract

The selectivity of yohimbine and its two diastereoisomers rauwolscine and corynanthine for pre- and postsynaptic alpha adrenoceptors has been 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 three 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. However, all the isomers were equipotent as antagonists of the diastolic pressure 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 broad 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. It is concluded that the high affinity of the antagonists yohimbine and rauwolscine for alpha-2 adrenoceptors is responsible for their selectivity because at the level of blockade of postsynaptic alpha-1 adrenoceptors both isomers were equipotent with corynanthine.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 219, Issue 2
1 Nov 1981
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Abstract

Pre- and postsynaptic alpha adrenoceptor selectivity studies with yohimbine and its two diastereoisomers rauwolscine and corynanthine in the anesthetized dog.

N B Shepperson, N Duval, R Massingham and S Z Langer
Journal of Pharmacology and Experimental Therapeutics November 1, 1981, 219 (2) 540-546;

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Abstract

Pre- and postsynaptic alpha adrenoceptor selectivity studies with yohimbine and its two diastereoisomers rauwolscine and corynanthine in the anesthetized dog.

N B Shepperson, N Duval, R Massingham and S Z Langer
Journal of Pharmacology and Experimental Therapeutics November 1, 1981, 219 (2) 540-546;
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