Peripheral antihistamine and central sedative effects of three H1-receptor antagonists

The effects of single oral doses of three antihistamine compounds on histamine-induced itch and flare reactions were studied in 24 healthy volunteers by a double-blind balanced design. Central sedative effects were concurrently analyzed using a set of computerized neuropsychological tests and analogue ratings. Hydroxyzine 20 mg had a more pronounced inhibitory effect on the cutaneous response than 3 mg clemastine or 3 mg azatadine. Clemastine tended to cause more sedation than the other two drugs. A compound score, reflecting the balance between peripheral and CNS effects, showed hydroxyzine to have relatively more peripheral antihistamine effect and less sedative effect than the other two drugs. The independence of peripheral and CNS antihistamine effects was also suggested by correlation analysis. Subjects displayed individual sensitivity to the peripheral antihistamine effect of the three drugs; a marked antihistamine effect of one drug predicted a marked effect of the other two drugs. This was not the case for CNS sedation. The independence of peripheral and CNS effects should encourage development of new and more specific antihistamine compounds.