Benzodiazepine-induced hyperphagia: stereospecificity and antagonism by pyrazoloquinolines, CGS 9895 and CGS 9896

Abstract

Non-deprived male rats were familiarized with a highly palatable diet until baseline consumption in a 30-min daily access period had stabilised. Stereospecificity of the hyperphagic effect of benzodiazepine receptor agonists was demonstrated using two enantiomers, the (S)-enantiomer being Ro11-3128 (methylclonazepam) and the (R)-enantiomer, Ro11-3624. The benzodiazepine receptor antagonists, Ro15-1788 and CGS 8216, reversed the hyperphagic effect of Ro11-3128. These data confirm the mediation of the hyperphagic effect of benzodiazepines by specific receptors. In further experiments, the effects of the pyrazoloquinolines CGS 9895 and CGS 9896 were examined both alone and also in combination with clonazepam. In doses of 1.25-10.0 mg/kg, neither CGS 9895 nor CGS 9896, when given alone, had a significant effect on the consumption of the palatable diet. Both, however, dose-dependently antagonised the hyperphagic effect of clonazepam. In a test of palatable food consumption, therefore, both compounds can be characterised as benzodiazepine antagonists.