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Cariprazine HCl
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Cariprazine HCl图片
CAS NO:1083076-69-0
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 463.87
Formula C21H33Cl3N4O
CAS No. 1083076-69-0 (HCl);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 10 mM in DMSO
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILES Code O=C(N[C@H]1CC[C@H](CCN2CCN(C3=CC=CC(Cl)=C3Cl)CC2)CC1)N(C)C.[H]Cl
Synonyms MP-214 HCl; MP 214 HCl; RGH188 HCl; RGH 188 HCl; MP214 HCl; GH-188 HCl; Cariprazine; trade name: Vraylar
实验参考方法
In Vitro

In vitro activity: Cariprazine hydrochloride is a novel and potent antipsychotic drug candidate that is in late-stage clinical development for the treatment of schizophrenia, as well as for bipolar disorder (manic/mixed and depressive episodes), and as an adjunctive agent for the treatment of major depressive disorder. Cariprazine is a dopamine D3-preferring D3/D2 receptor partial agonist that exhibits high affinity for the D3 receptor with Ki of 0.085 nM and D2 receptor with Ki of 0.49 nM, and moderate affinity for the 5-HT1A receptor with Ki of 2.6 nM. Cariprazine stimulates inositol phosphate (IP) formation with a high potency (pEC50 8.5) with relatively low efficacy (Emax 30%). Cariprazine stimulates inositol phosphate (IP) formation with a high potency (pEC50 8.5) with relatively low efficacy (Emax 30%.Cariprazine, a novel candidate antipsychotic, demonstrated approximately 10-fold higher affinity for human D3 versus human D2L and human D2S receptors (pKi 10.07, 9.16, and 9.31, respectively). Cariprazine displays high affinity at human serotonin (5-HT) type 2B receptors (pKi 9.24) with pure antagonism. Cariprazine has lower affinity at human and rat hippocampal 5-HT1A receptors (pKi 8.59 and 8.34, respectively) and demonstrates low intrinsic efficacy. Cariprazine displays low affinity at human 5-HT2A receptors (pKi 7.73). Moderate or low affinity for histamine H1 and 5-HT2C receptors (pKi 7.63 and 6.87, respectively) suggest Cariprazine's reduced propensity for adverse events related to these receptors.Cariprazine is over sixfold more potent (EC50=1.4 nM) than Aripiprazole (EC50=9.2 nM) in inhibiting isoproterenol-induced cAMP production in HEK-293 cells


Kinase Assay: These assays are done in 50 mM Tris (pH 7.4), 100 mM NaCl, 7 mM MgCl2, 1 mM EDTA, and 1 mM DTT. Assay tubes (final volume 250 μL) contain 50 μM (striatum and hippocampus) or 1 μM (D2 and D3 cell membrane) GDP, the ligand to be examined, and membrane suspension (250 μg tissue/tube for the striatum and hippocampus and 20 μg protein/tube for hD2 and hD3 membranes). Samples are preincubated for 10 min at 30°C. After the addition of 50 pM [35S]GTPγS, membranes are incubated for an additional 60 min at 30°C. Nonspecific binding is determined in the presence of 10 μM GTPγS; basal binding is determined in the presence of buffer only. The assay is terminated by rapid filtration through UniFilter GF/B using a harvester, and the membranes washed four times with 1 mL of ice-cold buffer. After drying (40°C for 1 h), 40 μL of Microscint is added to the filters, and the bound radioactivity is determined by a TopCount NXT counter


Cell Assay: Cells are seeded on a 24-well tissue culture plate in 500 μL of medium. Fifty microliters of medium containing 0.55 μCi myo-[3H]inositol is added (final concentration 1 μCi/mL) and incubated for 18-20 h. Cells are then washed three times with buffer containing 140 mM NaCl, 5 mM KCl, 2 mM CaCl2, 5 mM HEPES, 5 mM Na-HEPES, 20 mM glucose, and 10 mM LiCl (pH 7.4). Cells are then incubated for an additional 60 min (37°C) in medium with test compounds alone (agonist test) or alongside 1000 nM (±)-Quinpirole (antagonist test). Medium is then aspirated off, cells are lysed by adding 400 μL of 0.1 M HCl/2 mM CaCl2, and supernatants are frozen at –72°C. After thawing and centrifugation at 1000g for 10 min, 200 μL of each supernatant is loaded on 250 μL of AG1-X8 (formate form) anion exchange column. Effluent is discarded, and columns are washed twice in 1.5 mL of distilled water. IPs are eluted with 2.5 mL of 1 M ammonium formate/0.1 M formic acid directly into scintillation vials, 10 mL of Optiphase HiSafe 3 is added, and the radioactivity is determined in a TriCarb 4900 scintillation counter.

In Vivo A significant (P<0.01) reduction in ouabain-induced hyperactivity is observed after acute i.p. administration of all doses of Cariprazine (mean±SEM: 0.06 mg/kg, 64.2±3.88; 0.25 mg/kg, 72.7±11.67; 0.5 mg/kg, 40.6±5.32; 1 mg/kg, 19.5±8.78) and lithium (40.4±12.78), compared with ouabain injection alone (114.6±14.33). The highest Cariprazine dose produced significant sedation (72% inhibition for Cariprazine 1.0 mg/kg aCSF vs. saline aCSF; P<0.05).The effects of 5 doses of Cariprazine (ranging from 0.005 to 0.15 mg/kg) are examined on EPM behavior of wild-type mice. Whereas lower doses of Cariprazine (0.005 to 0.02 mg/kg) do not alter the time spent in open arms, the two higher doses (0.08 and 0.15 mg/kg) lead to a significant decline of this measure (ANOVA, (F(5,52)=4.20; p=0.0032)). Moreover, the two higher doses of Cariprazine also lead to a significant decrease in the total number of arm entries (F(5,52)=7.21; p=0.0001)) but this decrease in the total number of arm entries is largely accounted for by a significant decrease in the number of closed arm entries (F(5,52)=11.75; p=0.0001)). The two highest doses of Cariprazine (0.08 and 0.15 mg/kg) have significant effects on locomotor activity, but doses ranging from 0.005 to 0.02 mg/kg do not affect anxiety-like behavior or locomotor activity in the EPM test.
Animal modelWild-type C57Bl/6J mice
Formulation & DosageDissolved in saline, filter sterilized (Mice) with a dose of 0.005 to 0.15 mg/kg; dissolved in 0.9% saline (Rats) with dosed of 0.06, 0.25, 0.5, and 1.0 mg/kg via intraperitoneal (i.p.) injection
References J Pharmacol Exp Ther. 2010 Apr;333(1):328-40; Psychopharmacology (Berl). 2011 Dec;218(3):579-87; Psychopharmacology (Berl). 2013 Mar;226(1):91-100; Pharmacol Res Perspect. 2015 Feb;3(1):e00073; Adv Ther. 2013 Feb;30(2):114-26.