A specific acylating agent for the [3H]phencyclidine receptors in rat brain.

A derivative of phencyclidine (PCP, 1 in fig. 1) bearing an isothiocyanate moiety on the meta position of the aromatic ring (Metaphit, 3 in fig. 1) has been synthesized and identified as a rapid and specific site-directed acylating agent of the [3H]phencyclidine binding site in rat brain homogenates. The percentage of sites irreversibly inactivated by Metaphit was found to be the same in the hippocampus and striatum and the remaining sites were unaffected by Metaphit treatment under any conditions, suggesting that at least two distinct binding sites are present. An isomeric isothiocyanate derivative did not irreversibly inhibit [3H]phencyclidine receptors, indicating structural specificity for Metaphit in the inhibition of these receptors. The availability of Metaphit should greatly facilitate study of the structure and function of the phencyclidine receptors.