Pimavanserin is an inverse agonist of the serotonin (5-HT) receptor subtype 5-HT2A (IC50 = 1.86 nM; Ki = 0.5 nM).1 It is selective for 5-HT2A over a panel of 65 ion channels, enzymes, and receptors (Kis = >100 nM). Pimavanserin reduces head-twitch behavior and prepulse inhibition deficits induced by the 5-HT2A receptor agonist DOI in rats at doses of 3 mg/kg, p.o. and 1-10 mg/kg, s.c., respectively. It also exhibits antipsychotic-like activity, reducing hyperactivity induced by (+)-MK-801 in mice. Pimavanserin acts synergistically with haloperidol or risperidone to suppress (+)-MK-801-induced hyperactivity and attenuates haloperidol- and risperidone-induced catalepsy in rats.2 Formulations containing pimavanserin have been used for the treatment of psychosis in Parkinson's disease.3
1.Vanover, K.E., Weiner, D.M., Makhay, M., 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-hydroxytryptamine2A receptor inverse agonistJ. Pharmacol. Exp. Ther.318(2)910-918(2006) 2.Gardell, L.R., Vanover, K.E., Pounds, L., et al.ACP-103, a 5-hydroxytryptamine 2A receptor inverse agonist, improves the antipsychotic efficacy and side-effect profile of haloperidol and risperidone in experimental modelsJ. Pharmacol. Exp. Ther.322(2)862-870(2007) 3.Goldman, J.G., and Holden, S.Treatment of psychosis and dementia in Parkinson's diseaseCurr. Treat. Options. Neurol.16(3)281(2014)
















