INHIBITION OF HUMAN PLATELET 5-HYDROXYTRYPTAMINE UPTAKE BY TRICYCLIC ANTIDEPRESSIVE DRUGS . 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. 1969 Royal Pharmaceutical Society of Great Britain