Comparison of the relationship between structure and CNS effects for lorazepam, clonazepam and alprazolam

Eight healthy young males were administered single doses of lorazepam (4 mg), clonazepam (4 mg), alprazolam (2 mg) or placebo, and their performance on behavioral tasks was monitored for 7 h. Lorazepam and clonazepam impaired performance on subcritical tracking, a primarily neuromotor task, for 2-4 h longer than alprazolam. Although the duration of impairment of the digit symbol substitution task was less discrepant for the three drugs, clonazepam and lorazepam still affected performance for a longer period of time than alprazolam. The rapid development of acute tolerance was indicated by clockwise hysteresis curves for all the drugs on the SCT task and for clonazepam and alprazolam on the DSS task. The maximum effect, effect offset rate and duration of the drug effect are discussed in relation to molecular structure and receptor affinity.