1,4-BENZODIAZEPINE DERIVATIVES AS ANTICONVULSANT AGENTS IN DBA 2 MICE/

1. The behavioural and anticonvulsant effects of 10 1,4-benzodiazepine derivatives were studied after intraperitoneal administration in DBA/ 2 mice, a strain genetically susceptible to sound-induced seizures. 2. The anticonvulsant effects were evaluated on seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a perspex dome. The rank order of potency for anticonvulsant act ivity was alprazolam > clonazepam > flunitrazepam > diazepam > pinazep am > desmethyldiazepam > oxazepam > prazepam > halazepam > camazepam. 3. The impairment of locomotor performance following IP administration of the above reported derivatives was also evaluated by means of the rotarod test. 4. Hypothermic activity was observed after the highest d oses of the benzodiazepines studied. 5. The potency of various 1,4 ben zodiazepines as inhibitors of specific [H-3] flumazenil binding to mem branes from cerebellum or cortex was evaluated. In general, 1,4-benzod iazepines were active as anticonvulsants at micromolar range and inhib ited [H-3] flumazenil binding at nanomolar range. 6. The different deg ree of anticonvulsant activity and impairment of coordinated motor mov ements cannot be directly related to the benzodiazepine binding affini ty or to the lipophilicity of the compounds.