THE NATURE OF THE BINDING BETWEEN LSD AND A 5‐HT RECEPTOR: A POSSIBLE EXPLANATION FOR HALLUCINOGENIC ACTIVITY
British Journal of Pharmacology – June 01, 1974
Source: OpenAlex
Summary
LSD demonstrates a unique ability to mimic serotonin (5-HT) in stimulating fluid secretion in isolated salivary glands, with 68% of glands showing increased cyclic AMP levels. Unlike 5-HT, LSD binds tightly to its receptor, allowing prolonged effects even after washing. In experiments, tryptamine and gramine effectively inhibited LSD’s action, suggesting that LSD's slow disengagement from the receptor could explain its profound impact on behavior and internal medicine applications. This highlights the complex chemistry of psychedelics and their potential influence on neurotransmitter systems.
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.