LACK OF INTERACTION BETWEEN A NEW ANTIHISTAMINE, MIZOLASTINE, AND LORAZEPAM ON PSYCHOMOTOR PERFORMANCE AND MEMORY IN HEALTHY-VOLUNTEERS

1 The possible interaction between a new H-1 antihistamine, mizolastin e, and lorazepam was assessed in a randomised, double-blind, cross-ove r, placebo-controlled study involving 16 healthy young male volunteers who received mizolastine 10 mg or placebo once daily for 8 days with a 1 week wash-out interval, The interaction of mizolastine, at steady- state, with a single oral dose of lorazepam or placebo was assessed on days 6 or 8 of each treatment period. 2 Psychomotor performance and c ognitive function were evaluated using objective tests (critical flick er fusion threshold, choice reaction time, tapping, arithmetic calcula tion, body sway) and self-ratings (visual analogue scale, ARCI) before and at 2, 4, 6 and 8 h after dosing, Short-term memory (Sternberg mem ory scanning, immediate free recall of a word list) and long-term memo ry (delayed free recall and recognition of words and pictures) were as sessed before and at 3 h after dosing, Pharmacodynamic interactions we re evaluated by repeated measures ANOVA in a 2 x 2 factorial interacti on model. 3 Mizolastine, 10 mg once daily, at steady-state, was devoid of sedation and detrimental effect on skilled performance and memory. 4 In contrast, a single 2 mg dose of lorazepam produced marked impair ment of psychomotor performance, cognitive functions (significant redu ction in flicker fusion threshold, tapping and arithmetic calculation and increase in reaction times and body sway) and subjective sedation from 2 to 8 h after dosing. In addition, lorazepam induced an anterogr ade amnesia, characterised by a decrease in delayed free recall and re cognition, and a deficit in short term memory. 5 Mizolastine did not p otentiate the detrimental effect of lorazepam, The time course and the intensity of the disruption induced by the combination of lorazepam a nd mizolastine closely paralleled the changes induced by lorazepam alo ne.