Pimavanserin tartrate (formerly known as BVF036; ACP-103; BVF-036; Nuplazid), the tartrate salt of Pimavanserin, is a novel and orally bioactive inverse agonist of the 5-HT2A (serotonin receptor subtype 2A) receptor the has been approved in 2016 as an atypical antipsychotic for the treatment of Parkinson's disease psychosis.
Physicochemical Properties
| Molecular Formula | C54H74F2N6O10 |
| Molecular Weight | 1005.21 |
| Exact Mass | 1004.54 |
| Elemental Analysis | C, 64.52; H, 7.42; F, 3.78; N, 8.36; O, 15.92 |
| CAS # | 706782-28-7 |
| Related CAS # | Pimavanserin; 706779-91-1 |
| PubChem CID | 11672491 |
| Appearance | White to off-white solid powder |
| LogP | 7.868 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 14 |
| Rotatable Bond Count | 19 |
| Heavy Atom Count | 72 |
| Complexity | 657 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | O=C(NCC1=CC=C(OCC(C)C)C=C1)N(CC2=CC=C(F)C=C2)C3CCN(C)CC3.O=C(O)[C@H](O)[C@@H](O)C(O)=O.O=C(NCC4=CC=C(OCC(C)C)C=C4)N(CC5=CC=C(F)C=C5)C6CCN(C)CC6 |
| InChi Key | RGSULKHNAKTFIZ-CEAXSRTFSA-N |
| InChi Code | InChI=1S/2C25H34FN3O2.C4H6O6/c2*1-19(2)18-31-24-10-6-20(7-11-24)16-27-25(30)29(23-12-14-28(3)15-13-23)17-21-4-8-22(26)9-5-21;5-1(3(7)8)2(6)4(9)10/h2*4-11,19,23H,12-18H2,1-3H3,(H,27,30);1-2,5-6H,(H,7,8)(H,9,10)/t;;1-,2-/m..1/s1 |
| Chemical Name | (2R,3R)-2,3-dihydroxybutanedioic acid;1-[(4-fluorophenyl)methyl]-1-(1-methylpiperidin-4-yl)-3-[[4-(2-methylpropoxy)phenyl]methyl]urea |
| Synonyms | ACP-103 tartrate; ACP 103; BVF036; ACP-103; BVF-036; ACP103; Trade name: Nuplazid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | 5-HT2A ( pIC50 = 8.7 ) |
| ln Vitro | Pimavanserin hemitartrate competitively antagonizes the binding of [3H]ketanserin to heterologously expressed human 5-HT 2A receptors with an average pKi of 9.3 in membranes and 9.70 in whole cells. Pimavanserin hemitartrate demonstrated potent inverse agonist activity in a cell-based functional assay Receptor Selection and Ascending Technology (R-SAT) with an average pIC50 of 8.7. Pimavanserin hemitartrate exhibits low affinity (average pKi 8.80 in membranes and 8.00 in whole cells, determined by binding to ligand) and potency as an inverse agonist (average pIC50 7.1 in R-SAT) against human 5 -HT 2C absorption, lacks affinity and functional activity for 5-HT 2B absorption, dopamine D2 absorption and other human monoaminergic absorption [1]. |
| ln Vivo | Pimavanserin (3 mg/kg, p.o.) attenuates head twitches caused by DOI in rats. Pimavanserin (3 mg/kg, p.o.) significantly reduces the hyperactivity induced by MK-801 in mice. [1] Pimavanserin (40 mg/kg, i.p.) significantly reduces tacrine-induced tremulous jaw movements in a rat model of parkinsonian tremor. [2] |
| Animal Protocol |
Male Sprague-Dawley rats 3 mg/kg p.o. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the clinical use of pimavanserin during breastfeeding. If pimavanserin is required by the mother, it is not a reason to discontinue breastfeeding. However, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
| References |
[1]. J Pharmacol Exp Ther . 2006 May;317(2):910-8. [2]. Pharmacol Biochem Behav . 2008 Oct;90(4):540-4. |
| Additional Infomation |
Pimavanserin tartrate is a tartrate salt that is the hemitartrate salt of pimavanserin. An atypical antipsychotic that is used for treatment of hallucinations and delusions associated with Parkinson's disease. It has a role as an antipsychotic agent, a serotonergic antagonist and a 5-hydroxytryptamine 2A receptor inverse agonist. It contains a pimavanserin(1+). See also: Pimavanserin (has active moiety). |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9948 mL | 4.9741 mL | 9.9482 mL | |
| 5 mM | 0.1990 mL | 0.9948 mL | 1.9896 mL | |
| 10 mM | 0.0995 mL | 0.4974 mL | 0.9948 mL |