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

LSD mimics serotonin (5-HT) in stimulating fluid secretion, changing electrical potentials, and increasing cyclic AMP in isolated salivary glands of the blowfly Calliphora. Unlike serotonin, LSD disengages slowly from the receptor, causing continued secretion even after repeated washing. Both serotonin and tryptamine prevent LSD from acting, and bound LSD is slowly displaced by agonists like tryptamine or antagonists like gramine. The ability of LSD to remain tightly bound while still functioning as an agonist may explain its profound effects in the central nervous system.

Study at a glance

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.