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 H1 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Patat
A
A
Synthélabo Recherche, Clinical Research Department, Bagneux, France.
Perault
M C
MC
Vandel
B
B
Ulliac
N
N
Zieleniuk
I
I
Rosenzweig
P
P
D000328:Adult; D000704:Analysis of Variance; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects*
D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; C076170:mizolastine; D008140:Lorazepam