A comparison of triprolidine and clemastine on histamine antagonism and performance tests in man: implications for the mechanism of drug induced drowsiness.

The effects of triprolidine hydrochloride 1.25, 2.5 and 5 mg, clemastine 1 and 2 mg and lactose dummy administered orally, in a balanced order, at weekly intervals to 12 healthy volunteers, on the flare and weal responses to intradermal histamine injection, and also on both subjective effects and objective psychomotor tests were examined. The histamine response was significantly larger at 09.00 h falling through the day but increasing by late afternoon. Triprolidine produced a dose-related antagonism of both flare and weal response maximal at 3 h and wearing off after the lower doses at 8 h. Clemastine by contrast produced poor antagonism of histamine at 3 h but a marked effect at 5.5 and 8 h. Auditory vigilance was significantly (p less than 0.05) impaired by all doses of triprolidine 1 to 2 h after administration, but no change followed clemastine at this time. When tested 6 to 7 h after administration significant impairment followed both doses of clemastine but only the 5 mg dose of triprolidine. Both drugs prolonged reaction time in a dose-related manner at 2.5 and 5.0 h but the effects had worn off at 7 h. Digit symbol substitution was impaired by the top doses of both antihistamines but short term memory was unaffected. Subjective effects measured using analogue lines reflected the effects in the vigilance test, in that drowsiness and mental impairment were noted early after triprolidine, while clemastine produced maximal effects at 5 h. Subjects were ranked in order of magnitude of inhibition of both flare and weal, and impairment of vigilance, prolongation of reaction time and subjective drowsiness score. There was no indication of a significant correlation, using Spearman's test, between antagonism of histamine and effects on the central nervous system.