Phencyclidine receptors in rat brain cortex

Abstract

The binding of [ 3H]phencyclidine (PCP) to receptors in rat brain cortex has been studied. Two receptors have been detected, a high affinity receptor site with a k D of 23.5 ± 7.4 nM and a low affinity site with a k D of 7.6 ± 1.8 μM. The binding of [ 3H]PCP to its receptors was pH and temperature dependent and was destroyed by heat-denaturation. The binding of [ 3H]PCP was inhibited by compounds which produce PCP-like behavioral effects including dexoxadrol, etoxadrol and ketamine as well as a novel series of benz(f)isoquinolines. The low affinity site was blocked by PCP, etoxadrol and (+)-SKF-10,047 but not morphine or leu-enkephalin, suggesting that it also represents a specific PCP site. Stereoselective displacement of PCP at the high affinity receptor was observed with the isomers of cyclazocine, cyclorphan, SKF-10,047 and dioxadrol (dexoxadrol and levoxadrol). Naloxone, 4,5,6,7-tetrahydroisoxazolo (S,4-C)pyridin-3-ol (THIP) hydrate and haloperidol inhibited binding poorly ( K i >1 μM), suggesting that these compounds do not interact significantly with the high affinity PCP receptor in vivo. The affinity of ligands for the phencyclidine receptor was highly correlated ( r = 0.714, P < 0.01) with their potency to produce catalepsy in pigeons.