P2E105 - Mechanisms of neurotoxicity of substituted amphetamines

Abstract

A series of pharmacological trials conducted on AF 1161 are described. AF 1161 explicates, at doses much lower than toxic ones, certain effects on behaviour characterized by a picture of sedation and diminished reactivity to external stimuli. Even at very high doses, the drug does not provoke catatonia, paralysis, or a true hypnotic state. Death is preceded by a state of prostration, overtaken by clonic convulsion. The conditioned avoidance reflex in rats and reactions to different types of painful stimuli are inhibited at doses that scarcely influence general behaviour. Duration of sleep induced by hexobarbital is increased immediately after AF 1161 administration, but returns to normal after 24 hr. No significant hypothermic effect in normal animals was noted. Toxicity of amphetamine in grouped mice is inhibited. A depressant action on the linguomandibular reflex and, no a slight extent, on the knee jerk has been observed. AF 1161 possesses a very slight anti-histamine action, a moderate adrenolytic action and a powerful anti-serotonin action. Convulsions due to pentetrazol, electroshock and strychnine are not inhibited. A local anesthetic effect was also observed.These results are discussed, and possible therapeutic use in man of AF 1161 is postulated.