Antagonism of histamine-activated adenylate cyclase in brain by D-lysergic acid diethylamide.

Abstract

D-LSD and D-2-bromo-LSD were competitive antagonists of the histamine activation of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] in broken cell preparations of the hippocampus and cortex of guinea pig brain. The adenylate cyclase was linked to the histamine H2-receptor. D-LSD and D-2-bromo-LSD showed topological congruency with potent H2-antagonists. D-2-Bromo-LSD was 10 times more potent as an H2 antagonist than cimetidine, the most potent H2-antagonist reported, and D-LSD was about equipotent to cimetidine. Blockade of H2-receptors could contribute to the behavioral effects of D-2-bromo-LSD and D-LSD.