Serotonin binds specifically to calf caudate tissue with high affinity, having a dissociation constant of 2 nM and a binding site density of 14 fmoles per milligram of protein. Among many drugs tested, only serotonin agonists and antagonists inhibited this binding. Agonist potencies ranged from bufotenin (6 nM) to tryptamine (270 nM), and antagonist potencies from LSD (9.5 nM) to metergoline (25 nM).
Phencyclidine, ketamine, dizocilpine, and LSD all show higher affinity for the high-affinity state of the dopamine D2 receptor (D2High) than for the NMDA receptor. Phencyclidine had a Ki of 2.7 nM at D2High versus 313 nM at the NMDA receptor; ketamine had a Ki of 55 nM at D2High versus 3100 nM at NMDA sites; dizocilpine had a Ki of 0.3 nM at D2High versus a Kd of 1.8 nM at NMDA; LSD had a Ki of 2 nM at D2High. Because these psychotomimetics are more potent at D2High, their psychotomimetic action likely involves D2 agonism. In vivo, these drugs test a combined hyperdopamine and hypoglutamate theory of psychosis.