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 anticonvalsant (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 reflex 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 of 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.
