Pimavanserin tartrate (ACP-103) is a potent 5-HT 2A receptor inverse agonist with pIC50 and pKi of 8.73 and 9.3, respectively. pIC50: 8.73 (5-HT 2A)[1]pKi: 9.3 (5-HT 2A)[1]
Pimavanserin tartrate competitively antagonizes the binding of [3H]ketanserin to heterologously expressed human 5-HT 2A receptors with a mean pKi of 9.3 in membranes and 9.70 in whole cells. ACP- 103 displays potent inverse agonist activity in the cell-based functional assay receptor selection and amplification technology (R-SAT), with a mean pIC50 of 8.7. Pimavanserin tartrate demonstrates lesser affinity (mean pKi of 8.80 in membranes and 8.00 in whole cells, as determined by radioligand binding) and potency as an inverse agonist (mean pIC50 7.1 in R-SAT) at human 5-HT 2C receptors, and lacks affinity and functional activity at 5-HT 2B receptors, dopamine D2 receptors, and other human monoaminergic receptors[1].
Pimavanserin tartrate attenuates head-twitch behavior (3 mg/kg p.o.), and prepulse inhibition deficits (1-10 mg/kg s.c.) induced by the 5-HT2A receptor agonist in rats and reduces the hyperactivity induced in mice by the N-methyl-D-aspartate receptor noncompetitive antagonist, consistent with a 5-HT 2A receptor mechanism of action in vivo and antipsychotic-like efficacy. Pimavanserin tartrate demonstrates 42.6% oral bioavailability in rats[1].
[1]. Vanover KE, et al. Pharmacological and behavioral profile of N-(4-fluorophenylmethyl)-N-(1-methylpiperidin-4-yl)-N'-(4-(2-methylpropyloxy)phenylmethyl) carbamide (2R,3R)-dihydroxybutanedioate (2:1) (ACP- 103), a novel 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther. 2006 May;317(2):910-8.