The neuropharmacology of various diazepam antagonists

Abstract

Recently, compounds which bind avidly to benzodiazepine binding sites have been shown to possess diazepam antagonist properties. For example, the benzodiazepine RO 15–1788 and the pyrazoloquinoline CGS 8216 can antagonize the anxiolytic, sedative, muscle relaxant and anticonvulsant properties of diazepam. The beta-carbolines have also been shown to antagonize several actions of diazepam. Other compounds inclucling physostigmine, naloxone, bicuculline, picrotoxin, caffeine and theophylline, lack appreciable affinity for benzodiazepine binding sites but do antagonize at least some of the behavioral actions of diazepam. Their antagonist properties are probably the result of opposing pharmacological actions rather than direct receptor antagonism. Clinically, a potent safe diazepam antagonist could be used to reverse effects of diazepam overdose and to speed recovery of diazepamtreated patients after various out-patient procedures.