Relationship between the pharmacological effects of benzodiazepines and their in vivo binding sites in the brain of rats.

: To compare the in vitro pharmacological effect and in the brain distribution of benzodiazepines and phenobarbital, three group of sixty anesthetized rats (470-480 g) were administered 5 microCi of 3H-diazepam, 3H-flunitrazepam or 3H-phenobarbital. The rats were decapitated 3, 10, or 40 minutes after the intravenous injection of these drugs. Radioactivity of the tissue was measured and calculated as d.p.m./g. tissue. 3H-diazepam radioactivity in the brain-stem and hypothalamus was significantly higher than in the brain cortex 3 and 10 minutes after the injection. 3H-flunitrazepam radioactivity in the brain cortex was higher than in other regions. There was no significant decrease in 3H-phenobarbital brain concentration, even 40 minutes after injection. The distribution of benzodiazepine is closely related with its pharmacological effect, and this suggests that in vitro benzodiazepine binding sites are not responsible for the pharmacological action in vivo.