An attempt has been made to examine the effect of CS-370 (10-chloro-11b-(2-chlorophenyl)-2, 3, 5, 6, 7, llb-hexahydrobenzo[6, 7]-1, 4-diazepino[5, 4b]oxazol-6-one), a new benzodiazepinooxazol derivative on the CNS and to make a comparison with diazepam or chlordiazepoxide.
1. From 20-30 min after 10-20mg/kg of CS-370 (p. o.), EEGs in cats (chronic) and in rabbits (chronic, gallamine immobilized and encéphale isolé) showed a tendency to develop a slow wave. Diazepam also had a similar effect.
2. Cortical arousal response induced by stimulation of the posterior hypothalamus and midbrain reticular formation at high frequency in the rabbit was not influenced by CS-370 and diazepam up to 20mg/kg (p. o.).
3. In rabbits, CS-370 in dose of 20mg/kg (p. o.) increased amplitudes of the augmenting response, but did not influence the recruiting response even at 40mg/kg (p. o.). Diazepam was similar.
4. In chronic rabbits, the duration of afterdischarge in amygdala represented the biphasic change which consisted of the prolongation after 30min and the shortening from after 60min following 10mg/kg of CS-370 (p. o.), while diazepam had a depressing effect only.
5. CS-370 (20mg/kg p. o. or 2mg/kg i. v.) reduced the contraction of the nictitating membrane induced by stimulation of the posterior hypothalamus in cats, but not to peripherally elicited responses. Effect of chlordiazepoxide was weaker.
6. Of the subcortical potentials to the sciatic nerve stimulation in cats, the evoked potentials in the central gray, the red nucleus and the substantia nigra were depressed at 2mg/kg of CS-370 (i. v.), but the potentials in the midbrain reticular formation and the centre-median nucleus of the thalamus were not influenced. The response in the central gray particularly showed remarkable influence.
7. To the evoked potentials recorded in the central gray in cats, CS-370 in dose 2mg/kg (i. v.) depressed those induced by stimulation of the sciatic nerve, the vagal nerve and the posterior hypothalamus and increased that by the lateral hypothalamic stimulation. Potentials to stimulation of the lateral amygdaloid nucleus and the septum remained unchanged.
8. In low spinal cats, CS-370 in a dose of 10mg/kg (i. p.) had no effect on the mono- and polysynaptic reflexes, but an additional dose of 20mg/kg slightly suppressed these reflexes, while the dorsal root potential was essentially unchanged.
9. Remarkable suppression of precollicular decerebrate rigidity in the cat was observed from 40 min after 10mg/kg of CS-370 (i. p.). Doses of 5mg/kg of diazepam had the same effect, but chlordiazepoxide had no effect up to 40mg/kg.
10. The spontaneous discharges of r-motoneurons in precollicular decerebrate cats disappeared following 10mg/kg of CS-370 (i. p.). This effect appeared earlier in fibers with irregularly firing patterns.
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