The inhibition of human platelet 5-hydroxytryptamine uptake by tricyclic antidepressive drugs. The relation between structure and potency

Thirty-five compounds related to the antidepressive drug imipramine in chemical structure have been examined for their capacity to inhibit the uptake of 5-hydroxytryptamine by human platelets in vitro. Substitution by small-sized electropositive groups in positions 2 or 3 of a benzene ring gave compounds more active than the prototype, 3-chloroimipramine being five times as potent on this test. Alteration of the characteristic seven-membered ring of the antidepressive drugs reduced the activity while substitution in the basic side-chain destroyed it. The tertiary amines were more potent inhibitors than their demethylated derivatives. In this and other ways the active structure for the inhibition of 5-ht uptake by human blood platelets differs from that for the inhibition of noradrenaline uptake by the rat heart.