The effects of quazepam, triazolam, flunitrazepam and placebo, alone and in combination with ethanol, on day‐time sleep, memory, mood and performance

Abstract

Day-time sleep and residual effects of quazepam 15 mg, triazolam 0.25 mg, flunitrazepam I mg, and placebo, alone and in combination with ethanol, were studied using a randomized, double-blind, crossover, single-dose design. Eight healthy volunteers, four male and four female, aged 19-24 years, received each medication in the morning after a 'normal' sleep at home the preceding night.Quazepam and triazolam decreased the sleep onset when compared to placebo. The combination with ethanol did not change these findings. Quazepam and placebo showed less residual effects than triazolam and flunitrazepam at 4 hours after drug intake: in combination with ethanol at 4 and 6 hours. No significant differences in mood were found between the different 'treatments', except with regard to alertness for quazepam and placebo compared to flunitrazepam, alone and in combination with ethanol, all at 4 hours.The combination druglethano1 showed an increase in C,,, of the former and a delay in T,,,, when compared to drug alone. The study indicated few clinically useful correlations between clinical effect and plasma concentration.

A pharmacodynamic study of quazepam and triazolam

“…Our triazolam data confirm and extend previous pharmacodynamic studies performed according to our experimental paradigm (Baktir et al, 1983;Schlaginhaufen et al, 1984;Wickstrom and Godtlibsen, 1988;Sostmann et al, 1989) by showing a significant effect on all psychomotor tests. Overall, our findings suggest that triazolam, at 0.25 mg single oral dose, behaves as an 'objectively sedative' BZ.…”

“…In clinical and electroencephalographic studies, quazepam showed (at an oral dose of 15 mg) effective hypnotic activity and low toxicity (Tietz et al, 1979;Maiman, 1981;Uhthoff and Aggerwall, 1981;Goethe and Kader, 1982;Mendels and Stern, 1983;Winsauer et LEE., 1984;Mendels, 1985). Nevertheless, in two objective studies performed on a small number of healthy volunteers, the same single oral dose of quazepam, when given during the day, had the same effects as placebo on tests of neuromotor performance Wickstrom and Godtlibsen, 1988). It has been postulated that the high hypnotic specificity (which has been suggested to be mainly related to anxiolytic properties) and low central toxicity (measured as sedation and ataxia) of quazepam may result from the property of quazepam and the metabolite 2-oxoquaze-~~ t Author t o whom correspondence should be addressed pam to bind selectively to BZ1 receptors (Iorio et al, 1984;Wamsley et al, 1985).…”

“…Triazolam, another 'specific' hypnotic BZ, showed a different pharmacokinetic and pharmacodynamic profile in comparison to quazepam, causing a significant impairment of psychomotor performance when a single oral dose (0.25 mg) was given during the day (Baktir et al, 1983;Schlaginhaufen et al, 1984;Wickstrom and Godtlibsen, 1988;Sostmann et al, 1989).…”

“…The doses selected for this study were judged equivalent for their hypnotic effect as measured by means of the multiple sleep latency test (Wickstrom and Godtlibsen, 1988).…”

Flunitrazepam und Fahrtüchtigkeit

“…Neben epidemiologischen Studien tragen vor allem experimentelle Studien dazu bei, mithilfe geeigneter Testverfahren, wie Fahrsimulationstests [25,26], realen Fahrtests [27,28], psychomotorischen [29], kognitiven [29], das Gedächtnis betreffenden [30] und physiologischen Tests (EEG [31,32], Maddox-Wing-Test [5,6], Messung der sakkadischen Augenbewegungen [33]) sowie subjektiven Testverfahren [31] [5,6] Aiming Test -Feinmotorik [41] Amnesietest -Gedächtnis (Amnesie) [41,54] Auditory Reaction Time aRT Einfachreaktionszeit auf auditive Reize [31,41] Aufmerksamkeitsbelastungstest d2 d2 selektive Aufmerksamkeit (Durchstreichtest) [26] Aufmerksamkeits-Prüfgerät APG Vigilanz und geteilte Aufmerksamkeit [26] Card Sorting Test CS psychomotorische Leistung [31,41,46] Choice Reaction Time CRT Wahlreaktionszeit [27,39,40,46,49,52,55,58] Clinical Stabilometric Platform CSP Gleichgewicht und Vigilanz [37] Complex Memory Test CMT Kurz-und Langzeitgedächtnis [40] Continuous Subcritical Tracking Task CTT psychomotorische Koordination [42] Continuous Performance Task CPT Aufmerksamkeit [42] Coordination Test -Koordination [52] Critical Flicker Fusion Frequency CFF Aufmerksamkeit und Vigilanz [27,…”