Effects of opioid antagonists on anticonvulsant and hypnotic activity of benzodiazepines.

The influence of naloxone and naltrexone on the hypnotic and protective efficacy of diazepam, chlordiazepoxide, clonazepam and estazolam against electroshock- and pentylenetetrazole-induced seizures was studied in mice. Naloxone and naltrexone significantly decreased the anticonvulsant effects of diazepam and estazolam, but they did not changed that of chlordiazepoxide and clonazepam in electroshock-induced tonic hindlimb extension. Protective effects of benzodiazepines against pentylenetetrazole-induced seizures were slightly diminished by naloxone and naltrexone (16 mg/kg). Opioid antagonists were able to reduce the duration of benzodiazepines-induced sleep at high dose (32 mg/kg) only. These findings suggest that the endogenous opioid system may participate in antiepileptic effects of benzodiazepines but not in their hypnotic activity.