Pharmacologic activity of stereoisomers of 1-substituted 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines: Inhibition of 3H-dopamine accumulation by rat brain slices and lipolytic activity with isolated mouse fat cells

Abstract

A number of 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines related to dopamine were studied for their inhibitory effects on accumulation of 3H-dopamine by rat brain slices and for lipolytic activity with isolated mouse fat cells. The unsubstituted 6,7-dihydroxytetrahydroisoquinoline (ED 50 7.4 × 10 −5 M) and S-(−)-salsolinol (ED 50 7.5 × 10 −5 M) were the most effective inhibitors of 3H-dopamine accumulation. R-(+)-Salsolinol, R-(+)-tetrahydropapaveroline and S-(−)-tetrahydropapaveroline were less effective inhibitors (ED 50 17–22 × 10 −5 M). S-(−)-Tetrahydropapaveroline was a very effective lipolytic agent with isolated fat cells (ED 50 2.0 × 10 −7 M), whereas the R-(+)-form was inactive up to 10 −5 M. These data illustrate the importance of the absolute configuration at the 1-position of the tetrahydroisoquinoline ring for regulating some of the pharmacologic actions of these 6,7-dihydroxylated derivatives.