Structural relationships in the inhibition of [3H]tryptamine binding to rat brain membranes in vitro by phenylalkylamines

The ability of various phenylalkylamines to inhibit the binding of [3H]tryptamine to rat frontal/parietal cortical membranes was examined in vitro. Affinity for [3H]tryptamine binding sites improved as the alkyl side chain was extended to include four carbons or when a methoxy group was added at the para position of the ring. One compound, p-methoxyphenylpropylamine (IC50 = 3.6 nM), was as potent as unlabelled tryptamine as a displacing agent. Based on the unique structure-activity relationship obtained, it appears that [3H]tryptamine binding sites do not mediate the actions of phenethylamines on serotonin uptake or release.