Long-lasting anticonvulsant effects of diazepam in different mouse strains: correlations with brain concentrations and receptor occupancy.

There were marked strain differences in the duration of the protective effects of diazepam against the convulsant actions of penylenetetrazole and picrotoxin in mice. In no case was significant protection found at 12 h or longer, regardless of whether the incidence of or the latencies to myoclonus or tonic-clonic convulsions were considered. These behavioural differences could not be explained simply in terms of strain differences in benzodiazepine metabolism or in percent of receptor occupancy, as determined by the fractional displacement of 3H-flunitrazepam binding in vivo. It is suggested that there might be strain differences in the percent of receptor occupancy needed in order to produce an anticonvulsant effect.