DIFFERENT CENTRAL MEDIATION OF STIMULANT EFFECTS OF AMPHETAMINE AND ITS P-CHLORO ANALOGUE

After it had been shown that amphetamine and p-chloroamphetamine have a different influence on central monoamines, the former depleting noradrenaline, the latter 5-HT, the question of a different mode of action for the two compounds, being closely related in their pharmacological properties, was studied in mice using the locomotor effect evoked by both compounds. In the case of amphetamine, this could be suppressed by small doses of α-methyltyrosine as well as by higher doses of cyproheptadine for which an adrenolytic effect must be supposed, but it could not be suppressed by a depletion of the central 5-HT with p-chlorophenylalanine. This points to a purely adrenergic mediation of the effect of amphetamine. The locomotor effect of p-chloroamphetamine could be suppressed by depleting the central 5-HT with p-chlorophenylalanine, by low doses of the 5-HT antagonist cyproheptadine and by high doses of α-methyltyrosine. Thus, the p-chloro compound is dependent on 5-HT in order to exert its central stimulant effect, but an adrenergic link, supposedly lying behind the tryptaminergic one, is also involved. © 1968.