Pimavanserin

SKU: orb1306543

Description

Pimavanserin (ACP-103) is a selective 5-HT2A receptor inverse agonist (pIC50 ~8.7) used as an atypical antipsychotic. It is applied in research models of Parkinson's disease psychosis and has been studied in both in vitro functional assays and in vivo behavioral experiments.

Research Area

Neuroscience, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 706779-91-1
• MW: 427.55
• Purity: 99.69% (May vary between batches)
• Formula: C₂₅H₃₄FN₃O₂
• SMILES: N(CC1=CC=C(F)C=C1)(C(NCC2=CC=C(OCC(C)C)C=C2)=O)C3CCN(C)CC3
• Target: 5-HT Receptor
• Solubility: DMSO:85.83 mg/mL (200.75 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.68 mM)

Bioactivity

• Target IC50:
  5-HT2A:8.7(pIC50)
• In Vivo:
  Pimavanserin (ACP-103) is a potent and effective orally active 5-HT2A receptor inverse agonist, with a pharmacological profile indicating its potential as an antipsychotic. It mitigates 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 (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride in rats and reduces hyperactivity in mice caused by N-methyl-D-aspartate receptor antagonism via 5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) at dosages of 0.1 and 0.3 mg/kg s.c. and 3 mg/kg p.o., corroborating its in vivo mechanism of action through the 5-HT2A receptor and demonstrating antipsychotic-like effectiveness. Pimavanserin also exhibits oral bioavailability exceeding 42.6% in rats.
• In Vitro:
  Pimavanserin (ACP-103) competitively antagonizes the binding of [3H]ketanserin to human 5-HT2A receptors, with mean pKi values of 9.3 in membranes and 9.70 in whole cells. It shows lesser affinity (mean pKi of 8.80 in membranes and 8.00 in whole cells) and potency as an inverse agonist (mean pIC50 7.1 in R-SAT) at 5-HT2C receptors, and lacks affinity and functional activity at 5-HT2B receptors, dopamine D2 receptors, and other human monoaminergic receptors. Pimavanserin (ACP-103) is highly selective for 5-HT2A receptors, displaying affinity predominantly for 5-HT2C receptors and maintaining approximately 30-fold selectivity for 5-HT2A over 5-HT2C receptors, depending on the assay.
• Cell Research:
  Pimavanserin (ACP-103) is dissolved in DMSO and stored, and then diluted with appropriate media before use. For the whole-cell binding, 6 million human embryonic kidney 293T cells are plated in 10-cm dishes and transfected with 5 μg of plasmid DNA using Polyfect. Two days after transfection, cells are harvested with 10 mM EDTA, washed, and resuspended in binding buffer (1× DMEM with 0.1% bovine serum albumin). Then, 60,000 cells transfected with the 5-HT2A receptor or 20,000 cells transfected with the 5-HT2C-INI receptor are incubated at 37°C for 3 h in the presence of 5 nM radioligand ([3H]ketanserin for 5-HT2A receptors and [3H]mesulergine for 5-HT2C-INI receptors) and varying concentrations of ligands (total volume 100 μL in a 96-well plate). Cells are filtered onto a 96-well GF/B filter plate and washed with 300 mL of wash buffer (25 mM HEPES, 1 mM CaCl2, 5 mM MgCl2, and 0.25 M NaCl) using a Filtermate 196 harvester. The filter plates are dried under a heat lamp before addition of 50 μL of scintillation fluid to each well. Plates are counted on a TopCount. Separately, the hydrochloride salt form of Pimavanserin (10 μM) is evaluated at MDS Pharma Services for activity in a broad screen of radioligand binding assays at 65 different receptors.

Storage & Handling

• Storage: keep away from moisture,keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, Inhibitor, ACP103, ACP-103, ACP 103, 5-HT Receptor, 5HT Receptor, 5-HT2A, 5HTReceptor, 5-hydroxytryptamine Receptor, Pimavanserin, Serotonin Receptor

Compound Identifiers

PubChem CID

10071196