Sedation and histamine H1-receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

A.N. Nicholson, Peta A. Pascoe, Claire Turner, C.R. Ganellin, P.M. Greengrass, A.F. Casy & Amanda D. Mercer

Royal Air Force Institute of Aviation Medicine, Farnborough, Hampshire GU14 6SZ;

Department of Chemistry, University College London, 20 Gordon Street, London WC1H OAJ; **Pfizer Central Research, Sandwich, Kent CT13 9NJ and tSchool of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY

Abstract

1.      The effects of 10mg (+)- and (-)-chlorpheniramine and 5mg (+)- and (-)-dimethindene on daytime sleep latencies, digit symbol substitution and subjective assessments of mood and well-being were studied in 6 healthy young adult humans. Each subject also took 5mg triprolidine hydrochloride as an active control and two placebos.

2.      Daytime sleep latencies were reduced with triprolidine, (+)-chlorpheniramine and (-)-dimethindene, and subjects also reported that they felt more sleepy after (+)-chlorpheniramine and (-)-dimethindene. Performance on digit symbol substitution was impaired with (+ )-chlorpheniramine.

3.      Changes in measures with (-)-chlorpheniramine and (+)-dimethindene were not different from changes with placebo.

4.      In the present study, changes in measures of drowsiness and performance were limited to the enantiomers with high affinity for the histamine Hl-receptor. These findings strongly suggest that sedation can arise from H1-receptor antagonism alone, and provide further support for the belief that the histaminergic system is concerned with the regulation of alertness in man.

Keywords: Antihistamines; H -receptor antagonists; chlorpheniramine; dimethindene; stereoselective effects; sedation in man

Sumber : Br. J. Pharmacol. (1991), 104, 270-276

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