Cutaneous antihistaminic action of cetirizine and dose-related EEG concomitants of sedation in man

Abstract The cutaneous antihistaminic action (prick test; 1:100, 1:200 and 1:1000) and electroencephalographic (EEG) concomitants of sedation following the histamine H 1 receptor antagonist cetirizine (10- and 20-mg acute oral doses) and chlorpheniramine, 4 mg, were investigated in a cross-over, placebo-controlled study in healthy male 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 histamine-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 signs of sedation were never observed. An increase of the 6.5–14.5 Hz EEG power, with anterior scalp preponderance, was observed after chlorpheniramine or cetirizine 20 mg. This effect of cetirizine was accounted for by a substantial increase of power in the 6.5–8.0 Hz frequency subsegment and is regarded, for these experimental conditions, as an established 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 mechanisms modulating vigilance and of a threshold dose of cetirizine for sedative action is suggested.