Lack of behavioural toxicity of mizolastine: a review of the clinical pharmacology studies

First-generation H-1 antihistamines were associated with major sedative sid e-effects which were heavily disruptive to young active and aged patients w hen performing everyday activities. Mizolastine is a potent and selective H -1-receptor antagonist which slowly penetrates into the brain and thus lack s the sedative effects of earlier antihistamines. In this paper we present an overview of five clinical pharmacology studies which were carried out with a view to assessing mizolastine effects on psyc homotor and skilled performances, and on cognitive functions in young and a ged subjects. The studies were all randomized, double-blind, placebo and (with the except ion of one) active-drug controlled, cross-over studies. A total of 76 young and 15 aged subjects were enrolled. Two studies evaluated mizolastine over a range of doses (5-45 mg), and three involved a single or multiple admini strations of the therapeutic dose (10 mg/day). Comparators were first gener ation (clemastine, tripolidine) and second generation (terfenadine, cetiriz ine) antihistamines. Drug effects were evaluated through standardized psych ometric and memory tests, and subjective self-ratings (visual analogue scal es). In two studies, driving performance was assessed using an actual drivi ng test. Two studies investigated drug interaction with depressants of the central nervous system such as alcohol and lorazepam. The results of the five reported studies were consistent in that mizolastin e showed to be free from sedative effects when administered at the therapeu tic dose. As with other newly developed antihistamines, some changes occurr ed at higher dose levels. At the therapeutic dose mizolastine did not alter driving performance and did not potentiate the depressant effects of alcoh ol and lorazepam. Mizolastine was shown to be free from sedative effects that could affect th e safe performance of everyday life activities in young and aged patients w hen administered at the therapeutic dose.