THE NATURE OF THE BINDING BETWEEN LSD AND A 5‐HT RECEPTOR: A POSSIBLE EXPLANATION FOR HALLUCINOGENIC ACTIVITY

Abstract

(+)‐Lysergic acid diethylamide (LSD) mimicked 5‐hydroxytryptamine (5‐HT) in its ability to stimulate fluid secretion, to change transepithelial and intracellular potentials as well as to increase the cyclic 3′,5′‐adenosine monophosphate (cyclic AMP) concentrations of isolated salivary glands of Calliphora. Unlike 5‐HT, LSD disengages slowly from the receptor and fluid secretion continues despite repeated washing. Both 5‐HT and tryptamine prevented LSD from acting on the glands. LSD bound to the receptor was slowly displaced when glands were treated with agonists (tryptamine) or antagonists (gramine). The property of LSD which permits it to function as an agonist despite remaining tightly bound to the receptor is discussed as a possible basis for its profound effects within the central nervous system. 1974 British Pharmacological Society