The pinna reflex and its inhibition by clonidine: Relationship to sedation and quantitation of central α2-antagonist potency

Author:

Handley Sheila L1

Affiliation:

1. Drug Mechanisms Research Unit, Department of Pharmacy, University of Aston, Birmingham B4 7ET, UK

Abstract

Abstract The relationship between sedation and pinna reflex inhibition has been measured for a range of centrally acting drugs. Ability to abolish the pinna reflex was not related to sedative activity as assessed by a behavioural method. Thus, at equisedative doses, diazepam, haloperidol, mianserin, prazosin and indoramin failed to abolish the pinna reflex while phenobarbitone and chlorpromazine caused partial- and clonidine complete-inhibition. At the ED50 for pinna reflex inhibition, guanabenz and guanfacine were significantly less sedative than clonidine. Mepyramine, yohimbine, RS−21361, idazoxan and phenylephrine produced little or no sedation and did not inhibit the reflex. When these agents (except for guanabenz and guanfacine) were tested for their ability to prevent clonidine-induced pinna reflex inhibition, all except the drugs with α2-adrenoceptor antagonist activity were inactive. The potency order of the active agents was idazoxan > yohimbine > RS−21361 = mianserin. Antagonism of clonidine-induced pinna reflex inhibition may therefore prove to be a useful quantitative model for assessing the central potency of α2-adrenoceptor antagonists.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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