Elsevier

Life Sciences

Volume 28, Issue 6, 9 February 1981, Pages 653-660
Life Sciences

Correlations between central hypotensive and peripheral hypertensive effects of structurally dissimilar alpha-adrenoceptor agonists

https://doi.org/10.1016/0024-3205(81)90130-2Get rights and content

Abstract

The possible similarity between peripheral (vascular) and central α-adrenoceptors was investigated. For 12 structurally dissimilar α-adrenoceptor agonists, including clonidine, a correlation study is described between the adrenergic effects mediated by both types of α-adrenoceptors, i.e. hypotensive and hypertensive efficacies. Hypotensive activity was quantified by means of a pC25, calculated from log dose-response curves determined after intravenous administration to anaesthetized, normotensive rats. Accordingly, hypertensive potency was expressed as a pC60, established in pithed, normotensive rats. Apparent partition coefficients (log P′) were measured between octanol and buffer (pH=7.4; 37°C) to account for the difference in accessibility to both classes of α-adrenoceptors. A most significant, positive relationship was derived between pC25 and a linear combination of pC60 and log P′. This finding indicates a resemblance among the central and peripheral α-adrenoceptors excited by the drugs. The results are discussed and explained in the light of the recent identification of distinct populations of postsynaptic α1- as well as α2-adrenoceptors in peripheral vascular smooth muscle, both involved in drug-induced vasoconstriction.

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