Correlation between anorectic potency and affinity for hypothalamic (+)-amphetamine binding sites of phenylethylamines.

The potencies of a number of phenylethylamines and related compounds to inhibit food intake were compared with their relative affinities for hypothalamic (+)-amphetamine binding sites in vitro. There was a positive correlation (r = 0.78, P less than 0.001, n = 19) between potencies of these compounds to inhibit food intake and their potencies to inhibit [3H](+)-amphetamine binding. Individual enantiomers of amphetamine, ephedrine, norephedrine, pseudoephedrine and norpseudoephedrine all inhibited food intake with a two- to five-fold greater potency than that of their respective optical isomers. However, they did not exhibit a comparable stereospecificity to inhibit [3H](+)-amphetamine binding. Further, several compounds including imipramine and propranolol, without known anorectic properties were among the most potent agents to inhibit [3H](+)-amphetamine binding. Thus, although a positive correlation exists between relative binding affinity and potencies to inhibit food intake, the functional interrelationship is uncertain.