Studies on the relation of chemical structure to glycogenolytic activity in the brain

Abstract

The structure-activity relation (SAR) of β-phenylethylamine analogues and other drugs has been studied, in order to determine the molecular requirements for cerebral glycogenolytic activity in the mouse. The results suggest that for extensive cerebral glycogenolytic activity a β-phenylethylamine nucleus is necessary. Maximum stimulation of glycogenolysis occurred with a cyclopropyl group replacing carbon atoms 1 and 2 (tranylcypromine) or a methyl group on carbon atom 1 (amphetamine) of the alkylamine chain. There was no difference in the potency of the d- and d,l-isomers of amphetamine. Almost total loss of activity occurred if a substitution was made on the benzene ring, or the isopropyl chain of amphetamine. Adrenaline and noradrenaline, but not 5-hydroxytryptamine, increased the concentration of glycogen. Of the other drugs, only relatively large doses of LSD and methysergide caused a decrease in the content of glycogen. Morphine, nicotine and phencyclidine, in subconvulsant doses, did not deplete brain glycogen.