title: [Psycopharmacological and general pharmacological studies of 7-chloro-1-cyclopropylmethyl-1, 3-dihydro-5-(2-fluorophenyl)-2H-1, 4-benzodiazepin-2-one (KB-509) (author's transl)].
abstract: KB-509, a new derivative of benzodiazepines, increased locomotor activities of mice in doses of 8-32 mg/kg (p.o.) and a decrease occurred with higher doses. This drug was 3-6 and 1-2 times more potent than diazepam (DZP) and nitrazepam (NZP), respectively, in anticonvulsant (anti-pentylenetetrazol, bemegride, strychnine) activities, antiaggressive activity and potentiation of chlorprothixene-induced hypnosis in mice. On the other hand, KB-509 possessed similar potency to DZP and NZP in muscle relaxant activity in mice and inhibition of flexor in cats, and was markedly weaker than DZP and NZP in causing a loss of righting reflex in mice. In the spontaneous EEG activity, KB-509 induced a drowsy pattern and slightly inhibited arousal response to EEG in rabbits, as did DZP. In particular, KB-509 was more potent than DZP in suppressing the amygdala afterdischarge and had a longer duration of action. KB-509 and DZP slightly depressed body temperature, the cardio-respiratory system and the gastrointestinal tract in high doses. Potentiation of spontaneous motility of the uterus and increase of urine excretion were also observed with high doses. In conclusion, KB-509 is superior to both DZP and NZP in the ratio of anticonvulsant and/or taming activities and muscle relaxant activity, and has a weak central depressant activity.
mesh_terms: D000818:Animals; D000927:Anticonvulsants; D001341:Autonomic Nervous System / Q000187:drug effects; D001570:Benzodiazepinones / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects; D002415:Cats; D004064:Digestive System / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D012018:Reflex / Q000187:drug effects; D014590:Uterine Contraction / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D001570:Benzodiazepinones; C029163:flutoprazepam