TY - JOUR T1 - NEUROPHARMACOLOGIC EVALUATION OP OXILAPINE, A POTENT PSYCHOACTIVE AGENT JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 151 LP - 162 VL - 166 IS - 1 AU - CLINTON N. LATIMER Y1 - 1969/03/01 UR - http://jpet.aspetjournals.org/content/166/1/151.abstract N2 - The dibenzoxazepine-thiazepines have shown central nervous system activity in both laboratory and clinical testing. Oxilapine (2-chloro-11-(4-methyl-1-piperazinyl)-dibenz[b,f][1,4joxazepine) caused effective behavioral depression at doses of 0.05 to 5 mg/kg i.p. in a variety of laboratory animals. In spinal cat, doses of 025 mg/kg i.v. and 0.8 mg/kg/min enhanced the polysynaptic component of both gastrocnemius and peroneal ventral root reflexes and the polysynaptically mediated gastrocnemius-peroneal facilitation. Computer-averaged evoked potentials initiated by footpad, peripheral nerve or mesencephalic reticular formation stimulation in chloraloseanesthetized cats revealed enhancement at doses of 025 to 10 mg/kg i.v.; the higher doses initiated subcortical seizures which spread to the cerebral mantle. Electroencephalogram surveys showed reticular formation spike discharge leading to occlusive hippocampal amygdaloid seizure activity. Similar dosing in intact cats produced a decrease in motor behavior with tremor and ataxia. Chemical analyses of rat, cat and dog tissue showed a differential localization of compound: lung > brain > other. Diencephalic and mesencephalic reticular formation neurons apparently most susceptible to the drug also are in areas of the highest concentrations, suggesting that this agent acts to decrease the discharge threshold of neurons having low firing indices, thus affecting polysynaptically mediated responses. © 1969, by The Williams & Wilkins Company ER -