The benzodiazepine partial agonists, Ro16-6028 and Ro17-1812, increase palatable food consumption in nondeprived rats

Two novel imidazobenzodiazepines, Ro16-6028 and Ro17-1812, have been described recently as partial agonists acting at benzodiazepine receptors. In a test of palatable food consumption using nondeprived rats, Ro16-6028 (0.01-10 mg/kg) and Ro17-1812 (0.01-10 mg/kg) were shown to produce dose-dependent increases in food intake. Ro16-6028 was more potent than Ro17-1812. Suriclone, midazolam, and the beta-carbolines ZK 93423 and ZK 91296 also significantly increased food intake. The maximum effects of Ro16-6028 and Ro17-1812 were at least equivalent to those obtained with full agonists acting at benzodiazepine sites. Neither Ro16-6028 nor Ro17-1812 reduced locomotion or rearing frequency in an open field test, although there was a reduction in grooming frequency. In contrast, the full agonist midazolam dose-dependently reduced all measures of general activity. The results indicate that some novel benzodiazepine partial agonists strongly stimulate food intake in the absence of side effects typical of the classical benzodiazepines.