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Iloperidone is a novel psychotropic compound currently undergoing Phase III trials. Its affinity for human dopamine and 5-HT(2A) and 5-HT(2C) receptors has been reported previously. This report presents the affinity of iloperidone for a largely extended number of human neurotransmitter receptors. In a few instances human receptors were not available and receptor studies were performed on tissues from laboratory animals. The present data, supplemented with those of, indicate that iloperidone displays high affinity (K(I) &lt; 10 nM) for norepinephrine alpha(1)-adrenoceptors, dopamine D(3) and serotonin 5-HT(2A) receptors. Intermediate affinity (10-100 nM) was found for norepinephrine alpha(2C)-adrenoceptors, dopamine D(2A) and D(4) receptors and serotonin 5-HT(1A), 5-HT(1B), 5-HT(2C) and 5-HT(6) receptors. The affinity for all other receptors was below 100 nM, including norepinephrine alpha(2A), alpha(2B), beta(1), and beta(2), muscarine M(1)-M(5), histamine H(1), dopamine D(1) and D(5), CCK(A) and CCK(B), 5-HT(7), dopamine and norepinephrine transporters. Thus, iloperidone targets a selective set of dopamine, norepinephrine and serotonin receptor subtypes. The affinity for this particular set of receptors indicates that iloperidone has the potential to be a broad spectrum antipsychotic, with efficacy against positive, negative, depressive and cognitive symptoms of schizophrenia, and a low propensity to induce side effects.

neuropsychopharmacology

Extended Radioligand Binding Profile of Iloperidone A Broad Spectrum Dopamine/Serotonin/Norepinephrine Receptor Antagonist for the Management of Psychotic Disorders