The dopamine receptor: Differential binding of d-LSD and related agents to agonist and antagonist states

Dopamine receptor binding is calf striatal membranes of ³H-dopamine and ³H-haloperidol appears to differentiate agonist and antagonist states of the receptor. Agonists and antagonists have selective affinities for dopamine and haloperidol sites respectively. In evaluating relative affinities for dopamine and haloperidol binding sites, we have observed that d-LSD interacts with considerable affinity at the dopamine receptor. Its similar competition petition for binding of the two tritiated ligands suggests that it is a mixed agonist-antagonist, which is consistent with its interactions with the dopamine-sensitive adenylate cyclase. The effects of LSD on dopamine receptor binding are stereospecific, with d-LSD being 1,000 times more potent than d-LSD. 2-Bromo-LSD has more of an antagonist profile than d-LSD for the dopamine receptor. In binding experiments methiothepin behaves like a potent and relatively pure antagonist at dopamine receptors.