title: Pharmacological activity of novel alkylsulfonylaryl-1-substituted-1,4-benzodiazepine derivatives.
abstract: A series of 1-alkylsulfonylaryl-1,4-benzodiazepine derivatives were synthesized and assayed for their pharmacological profile. All the compounds tested exhibited a competitive antagonism of 3H-diazepam binding in cerebellum, cerebrum and submaxillary gland. Compound II (rec. INN tolufazepam) had a Ki of 12.7 nM in cerebrum and 400 nM in the submaxillary gland. It was very potent in preventing convulsions elicited by pentylenetetrazol (ED50 p.o.: 16.5 and ED50 i.v.: 20 mg/kg). This anticonvulsant action was suppressed by previous administration of Ro 15-1788. Compound II was also active in inhibiting suppressive behaviour in the test of Vogel. This compound has a relative low hypnogenic activity as well as a low potency to produce motor incoordination. Our results show that tolufazepam has a potential clinical usefulness.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D002467:Cell Nucleus / Q000378:metabolism; D006993:Hypnotics and Sedatives; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009420:Nervous System / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D013570:Synaptic Membranes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D013438:Sulfhydryl Compounds; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid