Rapid induction of lorazepam dependence and reversal with flumazenil.
Benzodiazepine tolerance, dependence and withdrawal are well established clinical entities although the pharmacological basis for these are still unclear. Recent data suggest that the primary event may be a change in efficacy at the benzodiazepine receptor. The present study demonstrates the rapid development of tolerance and dependence to lorazepam, defines its pharmacology in more detail, and shows that it may be rapidly reversed by treatment with the benzodiazepine antagonist flumazenil. These observations argue in favour of a receptor efficacy change underlying benzodiazepine tolerance and withdrawal and suggest a potential pharmacological treatment for this common and disabling clinical problem.
D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D005442:Flumazenil / Q000627:therapeutic use*; D008140:Lorazepam; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012640:Seizures / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000503:physiopathology*
D002243:Carbolines; D005442:Flumazenil; C035874:FG 7142; C036150:beta-carboline-3-carboxylic acid methyl ester; D008140:Lorazepam