Phencyclidine decreases binding capacity of serotonin₂ receptor in vitro

We have investigated that effects of phencyclidine (PCP) on [³H]-spiperone binding to synaptic membrane in the presence of sulpiride to distinguish serotonin (5-HT₂) receptor from dopamine₂ receptor. The amount of [³H]-spiperone specific binding was larger in the frontal and occipital cortices than in other areas. PCP strongly inhibited the [³H]spiperone binding at the concentration of 20 nM. Mescaline also weakly inhibited that, but not other hallucinogenic reagents such as methamphetamine, cyclazocine, scopolamine and atropine at the same concentration. In the presence of 20 n₃M PCP a significant decrease of Bmax and no change of Kd in the [³H]-spiperone specific binding was observed. Present results are consistent with the hypothesis that PCP may be a potent and selective agonist at 5-HT₂ binding sites. Although PCP known as hallucinogen interacts strongly with 5-HT₂ receptor, it is still too premature to draw any conclusions regarding a possible relationship between 5-HT binding and hallucinogenic potency.