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Effects of opioid antagonists on anticonvulsant and hypnotic activity of benzodiazepines
1Department of Pharmacodynamics, Medical Academy, Lublin, Poland.
Abstract:
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.
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