The effects of benzodiazepines on human opioid receptor binding and function

We performed in vitro studies to investigate the potential interaction of benzodiazepines with cloned human opioid receptor subtypes. Midazolam, chlordiazepoxide, and diazepam directly displaced [H-3]diprenorphine binding from kappa and delta receptors, but not mu receptors, whereas flumazenil was inactive. These benzodiazepines also stimulated S-35-GTP gammaS binding in membranes containing human kappa receptors, and the effect of midazolam was prevented by a selective kappa antagonist. Midazolam was also weakly active at delta -receptor activation, whereas all three were inactive at mu receptors. The results suggest that the analgesic efficacy reported for intrathecal benzodiazepines may be attributed, in part, to direct interaction with kappa -opioid receptors.