CUTANEOUS ANTIHISTAMINIC ACTION OF CETIRIZINE AND DOSE-RELATED EEG CONCOMITANTS OF SEDATION IN MAN

The cutaneous antihistaminic action (prick test; 1:100, 1:200 and 1:10 00) and neuropsychological and electroencephalographic (EEG) concomita nts of sedation following the histamine H-1 receptor antagonist cetiri zine (10- and 20-mg acute oral doses) and chlorpheniramine, 4 mg, were investigated in a cross-over, placebo-controlled study in healthy mal e volunteers (age 23-29 years). With an average C-max of cetirizine of 697.0 ng/ml (10 mg) and 1000.2 ng/ml (20 mg), the diameter of histami ne-induced skin weals was reduced by 24.0-74.9% depending on histamine concentration and with no dose dependence for cetirizine. Placebo and chlorpheniramine were ineffective. Behavioral or neuropsychological s igns of sedation were never observed. An increase of the 6.5-14.5 Hz E EG power, with anterior scalp preponderance, was observed after chlorp heniramine or cetirizine 20 mg. This effect of cetirizine was accounte d for by a substantial increase of power in the 6.5-8.0 Hz frequency s ubsegment and is regarded, for these experimental conditions, as an es tablished early EEG indication of mild sedation (vigilance 'stage A'). No EEG effects were observed after placebo or cetirizine at the 10 mg dose. The existence of some histaminergic (H-1) specificity of the me chanisms modulating vigilance and of a threshold dose of cetirizine fo r sedative action is suggested.