The effect of dopamine and other compounds on the activity of neurones ofHelix aspersa; Structure-activity relationships

Abstract

The effect of a series of phenylethylamine and related compounds has been investigated on the activity of specific neurones from the isolated brain of the snail,Helix aspersa. Dopamine and Epinine were the most potent of the compounds tested. Both compounds inhibited the spontaneous activity of the neurones and hyperpolarized the cell membrane potential. (−)-Noradrenaline and (−)-adrenaline were respectively twenty-five and ninety-two times less potent than dopamine. Isoprenaline had no effect on neurone activity.

Evidence is presented for a dopamine receptor as distinct from an action of dopamine on either an α or β adrenaline receptor. There are two specific requirements for this dopamine receptor: (a) two hydroxyl groups on the 3 and 4 position of the benzene ring; (b) the presence of a terminal nitrogen either unsubstituted or with one methyl group. The presence of an ethyl or an isopropyl group on the terminal nitrogen of dopamine reduces activity. Ethyldopamine and isopropyldopamine are respectively 106 and 193 times less potent than dopamine. The presence of a hydroxyl group β to the terminal nitrogen reduces dopamine-like activity.