Effects of zaleplon or triazolam with or without ethanol on human performance

Abstract 

Objectives and background: Given that non-selective γ-aminobutyric acid (GABA) agonist hypnotics impair performance and potentiate the disruptive effects of ethanol, this study was done to determine the performance-impairing and ethanol-potentiating effects of zaleplon, a new selective GABA agonist hypnotic.

Methods: Eighteen healthy men (12) and women (six), 31.5±5.6 years old, were studied. Each underwent six treatments of 2 days in duration, presented in a Latin square design with 2–12 recovery days between. The treatments were: placebo–placebo; placebo–ethanol; triazolam–placebo; triazolam–ethanol; zaleplon–placebo; and zaleplon–ethanol; with triazolam (0.25 mg) or placebo administered at 08:30 h, zaleplon (10 mg) or placebo at 09:00 h, and ethanol (0.75 g/kg) or placebo consumed from 09:30 h. Performance tests were completed each day at 10:30, 12:00 and 14:30 h.

Results: Breath ethanol concentration (BrEC), tested 0.5, 2.0, 4.5 and 6 h post consumption, did not differ among treatments and peaked at 0.052%, declining to 0.037, 0.009 and 0.001%. Triazolam with and without ethanol impaired digit symbol substitution, symbol copying, simple and complex reaction times and divided attention performance relative to placebo–placebo treatment. It did so consistently at 10:30 and 12:00 h, and less consistently at 14:30 h. Zaleplon without ethanol impaired only digit symbol substitution and divided attention tracking, and only at 10:30 h. Zaleplon with ethanol impaired most measures at 10:30 and 12:00 h, but not at 14:30 h. Zaleplon without ethanol consistently differed from triazolam without ethanol in the extent of performance impairment. Zaleplon with ethanol began to differ from triazolam with ethanol in performance impairment on the 12:00 and 14:30 h test sessions. Ethanol itself impaired most measures at 10:30 h, fewer at 12:00 h and none at 14:30 h. All active drug treatments increased self-rated sleepiness compared with placebo–placebo. Triazolam without ethanol produced greater self-rated sleepiness than zaleplon without ethanol. The addition of ethanol to both drugs generally produced comparable levels of self-rated sleepiness.

Conclusions: In an absolute sense, zaleplon produced less performance impairment and a shorter period of ethanol potentiation than triazolam.

Keywords:  Zaleplon, Triazolam, Ethanol potentiation, Performance impairment