Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics.
Molecular psychiatry September 1, 2005 P Seeman, F Ko, T Tallerico
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.