WAY-100635 has high selectivity for serotonin 5-HT1Aversus dopamine D4 receptors

The serotonin 5-HT1A receptor antagonist WAY-100635 was recently reported to have potent agonist properties at dopamine D4 receptors (Chemel et al., 2006, Psychopharmacology 188, 244–251.). Herein WAY-100635 (pKi at human (h) serotonin 5-HT1A receptors = 9.51; pKi at dopamine hD4.4 receptors = 7.42) stimulated [35S]GTPγS incorporation in membranes of Chinese Hamster Ovary cells expressing dopamine hD4.4 receptors with only moderate potency and modest efficacy (pEC50 = 6.63; Emax = 19% of dopamine). Moreover, in antagonism experiments, WAY-100635 had a much lower potency at dopamine hD4.4 receptors (pKB = 7.09), than at serotonin h5-HT1A receptors (pKB = 9.47). These data demonstrate that WAY-100635 has high selectivity for serotonin h5-HT1Aversus dopamine hD4.4 receptors.