A pharmacodynamic study of quazepam and triazolam

Abstract

A double-blind single oral dose study in 10 healthy volunteers was performed during the day to compare the diurnal effects of quazepam (15 mg) and triazolam (0.25 mg) on psychomotor performance. The central effect of the two benzodiazepines was assessed by means of a computer analysis of visually guided saccadic eye movements (SEM), critical flicker fusion threshold (CFFT), and choice reaction time (CRT). The results obtained suggest that: computer analysis of SEM is more sensitive than CRT and CFFT to detect sedative drug effects at a subclinical level; the presumed equipotent doses of quazepam and triazolam tested do not show the same sedative activity; the minimal impairment produced by quazepam on CNS function does not seem to be related to the property to bind to BZ1 receptors; the pharmacodynamic profile of quazepam seems to be characteristic of a 'non-sedative' agent, while triazolam behaves as a 'sedative' benzodiazepine.

A follow-up study of the acute behavioral effects of benzodiazepine-receptor ligands in humans: Comparison of quazepam and triazolam.

“…Quazepam impaired performance as a function of dose, and the absolute magnitude of this impairment was comparable to that observed with corresponding doses of triazolam. The present findings that quazepam and triazolam produced comparable dose-related performance impairment is discordant with three previous studies that have shown that quazepam produces less impairment than triazolam (Casucci et al, 1991;Nikaido & Ellinwood, 1987;Rush, Armstrong, et al, 1998). The reason for the discrepancy between these previous studies and the present experiment is likely due to the methods used.…”

“…In the first study, 15 mg quazepam produced significantly less performance impairment than did 0.25 mg triazolam (Nikaido & Ellinwood, 1987). In the second study, 15 and 30 mg quazepam produced significantly less performance impairment than did 0.5 and 1.0 mg triazolam (Casucci et al, 1991). In the third study, quazepam (15, 30, and 45 mg) produced less impairment than did triazolam (0.1875, 0.3750, and 0.5625 mg; Rush, Armstrong, et al, 1998).…”

“…Consistent with their different benzodiazepine-receptor binding profiles, the results of human behavioral pharmacology studies suggest that quazepam and triazolam are distinguishable in terms of their performance-impairing effects (Casucci, Di Costanzo, Riva, Allocca, & Tedeschi, 1991;Nikaido & Ellinwood, 1987;Rush, Armstrong, Ali, & Pazzaglia, 1998). In the first study, 15 mg quazepam produced significantly less performance impairment than did 0.25 mg triazolam (Nikaido & Ellinwood, 1987).…”

Pharmacological treatment effects on eye movement control

“…This reduction of saccade velocity is dose-dependent and a consistent log linear relationship with serum concentrations has been demonstrated for several drugs within this class (Bittencourt, Wade, Smith, & Richens, 1981; Hommer et al, 1986; Roy-Byrne, Cowley, Radant, Hommer, & Greenblatt, 1993). In a recent review of potential bio-markers of the effects of benzodiazepines in healthy individuals, de Visser et al (2003) reported that decreased saccade velocity was the most consistently reported effect, and one that has been shown to be far more sensitive to effects of benzodiazepines than visual analog scores (VAS) of alertness or neuropsychological measures of attention or psychomotor speed (Blom, Bartel, de Sommers, van der Meyden, & Becker, 1990; Casucci, Di Costanzo, Riva, Allocca, & Tedeschi, 1991; Salonen, Aaltonen, Aantaa, & Kanto, 1986). Despite the robustness of this effect, marked variability (as great as fourfold) in the magnitude of saccade peak velocity slowing after single administration of benzodiazepines has been reported (van Steveninck et al, 1992).…”