Anticonvulsant potency of unmetabolized diazepam

The anticonvulsant potencies of diazepam and its metabolites desmethyldiazepam and oxazepam against convulsions elicited by intravenous injection of pentetrazole were determined in mice at times from 1-30 min after intravenous administration. Diazepam had its maximal potency (ED50 0.53 mumol/kg) at 1 min when only traces of desmethyldiazepam could be detected in plasma and brain. During the next 30 min, the drug was rapidly transformed to desmethyldiazepam and oxazepam, and its anticonvulsant ED50 rose by a factor of about 4. From the concentrations in brain at 50% protection, a potency ratio of 1.0:0.37:0.33 could be calculated for diazepam, desmethyldiazepam and oxazepam.