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, mizolastine, and lorazepam was assessed in a randomised, double-blind, cross-over, 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 cognitive function were evaluated using objective tests (critical flicker fusion threshold, choice reaction time, tapping, arithmetic calculation, body sway) and self-ratings (visual analogue scale, ARCI) before and at 2, 4, 6 and 8 h after dosing, Short-term memory (Sternberg memory scanning, immediate free recall of a word list) and long-term memory (delayed free recall and recognition of words and pictures) were assessed before and at 3 h after dosing, Pharmacodynamic interactions were evaluated by repeated measures ANOVA in a 2 x 2 factorial interaction 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 impairment of psychomotor performance, cognitive functions (significant reduction 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 anterograde amnesia, characterised by a decrease in delayed free recall and recognition, and a deficit in short term memory. 5 Mizolastine did not potentiate the detrimental effect of lorazepam, The time course and the intensity of the disruption induced by the combination of lorazepam and mizolastine closely paralleled the changes induced by lorazepam alone.