D(1)-RECEPTOR ANTAGONISTS - COMPARISON OF [H-3] SCH39166 TO [H-3] SCH23390

A radiolabeled form of the benzonaphthazephine, SCH39166 was used to characterize the binding of this D1 antagonist in cortex, and an autoradiographic comparison of the localization of [H-3]SCH39166 to [H-3]SCH23390 (D1 antagonist and forerunner of SCH39166) binding was performed. The K(d) for [H-3]SCH39166, calculated from dissociation and association rate constants (1.09 nM), was comparable to the K(d) value derived from Scatchard analyses of saturation data (1.74 nM). [H-3]SCH39166 binds to brain tissue in a saturable manner with high affinity and low non-specific binding. Inhibition of [H-3]SCH39166 binding by dopaminergic and serotonergic agents supports the hypothesis that this is indeed a D1-specific compound with little overlap onto serotonin (5-HT) receptors. The affinity of [H-3]SCH39166 for 5-HT2 and 5-HT1c receptors is at least an order of magnitude lower than the affinity of [H-3]SCH23390 for these same receptor sites. Quantitative autoradiographic analysis of [H-3]SCH39166 and [H-3]SCH23390 binding indicates high D1-receptor density in the caudate-putamen, nucleus accumbens, olfactory tubercle, substantia nigra and entopeduncular nucleus. Low levels of binding (not significantly above background) were detected with [H-3]SCH39166 in lamina IV of the cortex and in choroid plexus; areas which had significant [H-3]SCH23390 binding and are known to have a high density of 5-HT (5-HT2 and 5-HT1c respectively) receptors.