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The affinity of mosapramine, an iminodibenzyl antipsychotic, to dopamine D3-receptors in rat brain was investigated by quantitative autoradiography of [3H]-7-OH-DPAT, a selective D3-ligand. Autoradiograms showed restricted distribution of [3H]7-OH-DPAT binding sites, with very high levels on the islands of Calleja (ICj), olfactory tubercle (Tu) and nucleus accumbens, while low but distinct labeling was observed in the molecular layer of lobule 10 of the cerebellum and caudate putamen (CPu). Binding of [3H]7-OH-DPAT completely disappeared when 1 microM dopamine was added, and it was reduced by the addition of mosapramine in a concentration-dependent manner. The displacing effect of mosapramine was more potent than that of haloperidol or clozapine in the brain regions examined. Mosapramine showed more potent affinity to receptors in Tu and ICj than those in CPu. On the other hand, haloperidol and clozapine did not show such regional differences. These results suggest that the high affinity of mosapramine to D3-receptors participates in, at least in part, the development of the clinical effects of mosapramine.

Quantitative autoradiographic analysis of the binding of mosapramine to dopamine D3-receptors.