Zolpidem and triazolam interact differentially with a delay interval on a digit-enter-and-recall task

Zolpidem (AMBIEN (R)), an imidazopyridine, is now the most commonly prescri bed hypnotic in the United States. Zolpidem is neuropharmacologically disti nct from benzodiazepine hypnotics in that it binds with low affinity to alp ha5-containing GABAA-receptor subtypes. Despite its unique benzodiazepine-r eceptor binding profile, the results of most of the published studies condu cted with humans suggest that the absolute magnitude of impairment produced by zolpidem is comparable to that observed with benzodiazepine hypnotics l ike triazolam. The present study compared the acute effects of zolpidem (0, 7.5, 15 and 22.5 mg) and triazolam (0, 0.1875, 0.375 and 0.5625 mg) in 10 non-drug-abusing humans using a; Digit-Enter-and-Recall task with varying d elay intervals (0, 10 and 20 s). To more fully characterize the behavioral effects of zolpidem and triazolam, several other performance tasks and subj ect-rated drug-effect questionnaires were included. Zolpidem and triazolam impaired performance on the Digit-Enter-and-Recall task as a function of do se under all delay intervals. However, the dose-related effects of the drug s interacted differentially with the delay interval such that zolpidem prod uced significantly less impairment than triazolam following the longest del ay (i.e., 20 s). Zolpidem and triazolam produced comparable dose-related im pairment on the digit symbol substitution test (DSST), circular lights' tas k, and picture recall/recognition task. Zolpidem and triazolam generally pr oduced qualitatively and quantitatively similar subject-rated drug effects, although some between-drug differences were observed. Consistent with the pharmacokinetics of these drugs, the effects of zolpidem peaked sooner and were shorter in duration than those observed with triazolam. The results of this experiment suggest that zolpidem may have less potential than triazol am to impair recall, which may be due to differences between these compound s in terms of their benzodiazepine-receptor binding profile. The results of the present study are also concordant with previous studies that found tha t drugs that act at the GABAA-receptor complex can be differentiated based on their interaction with the delay interval on a Digit-Enter-and-Recall ta sk. Copyright (C) 2001 John Wiley & Sons, Ltd.