Experimental Study on the Pharmacology of N-(α-Methyl-3, 4-methylenedioxyphenethyl) propionamide.

Abstract

General pharmacology of N-(α-methyl-3, 4-methylenedioxyphenethyl) propionamide (SA-8), previously synthesized by us, was described with emphasis at the effects on central nervous system. SA-8 reduced the spontaneous and methamphetamine-induced locomotor activity of mice rather stronger than meprobamate did. SA-8 did not protect mice from tonic convulsion and death by infused pentylenetet razol. It had hypothermic effect in rast but no antipyretic effect in rabbits at higher doses. SA-8 itself had weak specificity for the conditioned avoidance response in rats, but it markedly potentiated the effect of chlorpromazine on the response. The influence of SA-8 on the EEG in curarized cats was investigated. SA-8, administered intravenously, at small doses (20∼40mg./kg.) depressed spontaneous activities of cortex and hippocampus, but at larger doses (60∼90mg./kg.), it activates cortex and reticular formation, and if further doses were injected, seizure discharges throughout the whole brain occurred. Studies by means of electrical stimulation revealed that SA-8 in small doses depressed the hypothalamic activating system, but that it little affected the reticular activating system in cats. SA-8 antagonized to the depressive effect of hexobarbital on the electrical activity of brain in cats, contrary to the results reported in previous paper that SA-8 prolonged the hexobarbital induced sleep in mice. SA-8 had little spasmolytic activity in vitro in mice. It lowered blood pressure in cats. LD50 value of orally administered SA-8 was 450mg./kg. (357∼567, p=0.05).