Comparison of the effects of quazepam and triazolam on cognitive-neuromotor performance

Abstract

The pharmacological activity of quazepam, a BZ1 specific benzodiazepine, was compared to the effects of triazolam, a BZ1, BZ2 nonspecific benzodiazepine. Using a double-blind procedure, single oral doses of quazepam (15 or 30 mg), triazolam (0.5 or 1.0 mg) and placebo were administered to 21 healthy young men according to a random Latin square design balanced for order of drug administration. The drug effects on the performance of motor coordination and cognitive tasks were monitored for 7 h following drug ingestion. The results did not indicate any differential effects on cognitive-neuromotor performance for the BZ1 specific quazepam and 2-oxoquazepam compared with the BZ1, BZ2 nonspecific N-desalkylflurazepam metabolite. The impairment magnitude for 30 mg quazepam was closer to that of 0.5 mg triazolam. The onset of the initial drug effect was considerably slower for quazepam than for triazolam. The time course of the impairment profiles for the tasks was compared to pharmacokinetic data from previous studies and suggested that published pharmacokinetic rate constants explain only a limited portion of the impairment time course. In particular, the performance scores were already showing recovery from peak impairment 2 h post-drug ingestion, although quazepam's potent N-desalkylflurazepam metabolite has been found to maintain a maximum plateau level from 2 to 24 h.

Comparison of hangover effects among triazolam, flunitrazepam and quazepam in healthy subjects: A preliminary report

“…As for CPT, no significant between‐drug differences were observed. In previous studies assessing the acute effects of benzodiazepines on psychomotor performance, it was demonstrated that the time course of the impairment profiles was not concordant with the pharmacokinetic findings 20,32 . In particular, the peak latency of the psychomotor impairment occurred much earlier than that expected by the pharmacokinetic data published for quazepam; that is, <2 h 20 .…”

“…In previous studies assessing the acute effects of benzodiazepines on psychomotor performance, it was demonstrated that the time course of the impairment profiles was not concordant with the pharmacokinetic findings 20,32 . In particular, the peak latency of the psychomotor impairment occurred much earlier than that expected by the pharmacokinetic data published for quazepam; that is, <2 h 20 . The high lipophilicity profiles of the bezodiazepines adopted in the present study may well lead to a short duration of clinical action despite their various elimination half‐lives, resulting in a lack of prominent hangover effects on CPT indices.…”

“…It occurred rather restrictively in the afternoon, not in the morning, and was generally limited to the first few days (5–7 days) of administration 19 . Although more prominent hangover effects might be expected from its long elimination half‐life, it has been argued that the extensive distribution of quazepam and one of its major active metabolites, 2‐oxoquazepam, into fat and other peripheral compartments may have contributed to the lower magnitude of sedative and hangover effects 20 …”

The use of microcomputer‐based psychomotor tests for the evaluation of benzodiazepine effects on human performance: a review with emphasis on temazepam.

“…Choice reaction time seems to be sensitive to the effects of benzodiazepines under the same types of conditions seen with simple reaction time tests. Those studies that evaluate the effects of a benzodiazepine within the time frame of the half-life of a therapeutic dose of the parent compound typically detect impairment with these tests (Nikaido & Ellinwood, 1987;Preston et al, 1988;Roache & Griffiths, 1987;Seppala et al, 1976;Subhan et al, 1986;Warot et al, 1987). In a study by Schaffler & Klausnitzer (1989) impairment was noted with a subchronic dose of bromazepam over a 7 day period but in a study by Preston et al (1988) subtherapeutic doses of lorazepam did not impair choice reaction time performance.…”

“…Sinusoidal patterns are commonly used and the performance measurement is usually the subjects deviation from the generated wave summed over the entire test pattern. Tracking tasks, like reaction time tests, evaluate skills that are affected by hypnotic doses of benzodiazepines only a short period of time after administration (Nikaido & Ellinwood, 1987;Linnoila et al, 1990;Stoller et al, 1976;Subhan et al, 1976). In many studies a reduction in tracking ability was observed 2 to 4 h after drug administration but not the morning following either a single dose or a number of consecutive evenings administration of the same dose (Erwin et al, 1986;Fisch et al, 1990;Laurell & Tornros, 1986;Linnoila et al, 1981;Mattila, 1988;Mattila et al, 1988b;Nicholson, 1979Nicholson, , 1986.…”