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Ocaperidone (R-79598; R79598) is a potent and effective benzisoxazolyl piperidine neuroleptic and antipsychotic acting as an antagonist of 5-HT2, dopamine D2 and a 5-HT1A, with Ki values of 0.14 nM, 0.46 nM, 0.75 nM, 1.6 nM and 5.4 nM for 5-HT2, a1-adrenergic receptor, dopamine D2, histamine H1 and a2-adrenergic receptor, respectively.
Physicochemical Properties
| Molecular Formula | C24H25FN4O2 | |
| Molecular Weight | 420.49 | |
| Exact Mass | 420.196 | |
| Elemental Analysis | C, 68.55; H, 5.99; F, 4.52; N, 13.32; O, 7.61 | |
| CAS # | 129029-23-8 | |
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| PubChem CID | 71351 | |
| Appearance | White to off-white solid powder | |
| Density | 1.34g/cm3 | |
| Boiling Point | 588ºC at 760mmHg | |
| Melting Point | 180-184°C | |
| Flash Point | 309.4ºC | |
| Vapour Pressure | 8.36E-14mmHg at 25°C | |
| Index of Refraction | 1.667 | |
| LogP | 3.951 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 6 | |
| Rotatable Bond Count | 4 | |
| Heavy Atom Count | 31 | |
| Complexity | 856 | |
| Defined Atom Stereocenter Count | 0 | |
| SMILES | O=C1C(CCN2CCC(C3=NOC4=C3C=CC(F)=C4)CC2)=C(C)N=C5N1C=CC=C5C |
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| InChi Key | ZZQNEJILGNNOEP-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C24H25FN4O2/c1-15-4-3-10-29-23(15)26-16(2)19(24(29)30)9-13-28-11-7-17(8-12-28)22-20-6-5-18(25)14-21(20)31-27-22/h3-6,10,14,17H,7-9,11-13H2,1-2H3 | |
| Chemical Name | 3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-2,9-dimethylpyrido[1,2-a]pyrimidin-4-one | |
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| 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 |
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| 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-HT2 Receptor ( Ki = 0.14 nM ); D2 Receptor ( Ki = 0.75 nM ); 5-HT1A Receptor ( pEC50 = 7.6 ); 5-HT1A Receptor ( pKi = 8.08 ); a1-adrenergic receptor ( Ki = 0.46 nM ); Histamine H1 ( Ki = 1.6 nM ); a2-adrenergic receptor ( Ki = 5.4 nM ) | |
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| ln Vivo |
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| Enzyme Assay | It uses frozen HA7 cells to prepare the membranes. Following cell harvesting, they are homogenized in ice-cold Tris-HCl pH 7.4, 4°C for 10 minutes, and then centrifuged at 40000×g. Following another centrifugation, the pellet is suspended in the same buffer. Following a second centrifugation, the pellet is suspended in an assay buffer made up of Tris-HCl (50 mM, pH 7.4), pargyline (10 μM), and CaCl2 (4 mM). The [3H] 8-OH-DPAT (1 nM final concentration) and ocaperidone at seven concentrations are incubated with membrane protein (0.031-0.084 mg/tube) for 30 minutes at room temperature. Filtration through Whatman filters stops the reaction, and liquid scintillation spectrometry measures the amount of radioactivity. Triples are used to conduct the experiments. Non-linear curve fitting software, EBDA/LIGAND, is used to analyze data. The means of three determinations are included in the results expressed as pKi values[3]. | |
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| References |
[1]. In vitro and in vivo receptor binding and effects on monoamine turnover in rat brain regions of the novel antipsychotics risperidone and ocaperidone. Mol Pharmacol. 1992 Mar;41(3):494-508. [2]. Agonist, antagonist, and inverse agonist properties of antipsychotics at human recombinant 5-HT(1A) receptors expressed in HeLa cells. Eur J Pharmacol. 2001 Dec 14;433(1):55-62. [3]. The discriminative stimulus properties of buspirone involve dopamine-2 receptor antagonist activity. Psychopharmacology (Berl). 1993;111(1):55-61. |
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| Additional Infomation |
Ocaperidone is a pyridopyrimidine. Drug Indication Investigated for use/treatment in schizophrenia and schizoaffective disorders. Mechanism of Action Ocaperidone is a benzisoxazol piperidine antipsychotic primarily binds and with high affinity to 5-HT2 (serotonin) receptors, alpha1 and alpha 2 adrenergic receptors, dopamine D2 receptors and histamine H1 receptors. Ocaperidone is an antagonist primarily at the 5HT and D2 receptors. A proposed mechanism of action is the central D2 receptor blockade which is common to all neuroleptics that are used to treat positive symptoms of schizophrenia. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (3.97 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 16.7 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: 1.67 mg/mL (3.97 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3782 mL | 11.8909 mL | 23.7818 mL | |
| 5 mM | 0.4756 mL | 2.3782 mL | 4.7564 mL | |
| 10 mM | 0.2378 mL | 1.1891 mL | 2.3782 mL |