Autoradiographic characterization of binding sites for [3H]NE-100 in guinea pig brain

The receptor binding specificity and neuroanatomical distribution of ³H]NE-100 (N, N- dipropyl-2- 4- methoxy-3- (2- phenylethoxy) phenyl] ethylamine monohydrochloride)-labeled sigma receptor in guinea pig brain were examined using quantitative autoradiography. NE-100 potently inhibited ³H]NE-100 binding to slide-mounted sections of guinea pig brain with the IC₅₀ value of 1.09 nM, therefore, NE-100 apparently has high affinity binding sites. Competition studies, under conditions similar to those used to visualize the receptor, yielded the following rank order of potency: NE-100 > haloperidol > DuP734 > (+)pentazocine ? (?)pentazocine. Non-sigma ligands such as phencyclidine (PCP), MK-801 and (?)sulpiride had negligible affinities for ³H]NE-100 binding sites. High densities of ³H]NE-100 binding sites displaceable by haloperidol were present in the granule layer of the cerebellum, the cingulate cortex, the CA3 region of the hippocampus, the hypothalamus and the pons. The distribution of ³H]NE-100 binding sites was consistent with that of ³H](+)pentazocine, a sigma₁ ligand. These sigma sites may possibly be related to various aspects of schizophrenia.