Cariprazine HCl

Alias: MP-214 HCl; MP 214 HCl; RGH188 HCl; RGH 188 HCl; MP214 HCl; GH-188 HCl; Cariprazine; trade name: Vraylar

Cat No.:V2902 Purity: ≥98%

COA Product Data Instructions for use SDS

Cariprazine HCl Chemical Structure CAS No.: 1083076-69-0
Product category: Dopamine Receptor

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of Cariprazine HCl:

Cariprazine

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Top Publications Citing lnvivochem Products

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Cell 2020,183:1202-1218.e25.

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Cell 2020,183:1202-1218.e25.

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Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Cariprazine HCl (formerly MP-214; RGH-188; MP214; RGH188; Vraylar; Reagila), the hydrochloride salt of cariprazine, is an antipsychotic medication that has been approved 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 partial agonist of the D3/D2 receptors that selectively binds to the D3 receptor (Ki of 0.085 nM), the D2 receptor (Ki of 0.49 nM), and the 5-HT1A receptor (Ki of 2.6 nM). It is a dopamine D3-preferring receptor. Cariprazine has a relatively low efficaciousness (Emax 30%) but a high potency (pEC50 8.5) in stimulating the formation of inositol phosphate (IP).

Biological Activity I Assay Protocols (From Reference)

Targets

D₂ Receptor ( Ki = 0.49 nM ); D₃ Receptor ( Ki = 0.085 nM ); 5-HT_1A Receptor ( Ki = 2.6 nM )

ln Vitro

In vitro activity: Cariprazine has a relatively low efficaciousness (E_max 30%) but a high potency (pEC50 8.5) in stimulating the formation of inositol phosphate (IP).[2]. The novel candidate antipsychotic carriprazine showed a roughly ten-fold greater affinity for the human D₃ receptor compared to the human D_2L and D_2S receptors (pK_i 10.07, 9.16, and 9.31, respectively). With pure antagonistic properties, capiprazole exhibits a high affinity for human serotonin (5-HT) type 2B receptors (pK_i 9.24). Cariprazine exhibits low intrinsic efficacy and lower affinity at the rat and human hippocampal 5-HT_1A receptors (pK_i 8.59 and 8.34, respectively). The affinity of capriprazine for human 5-HT_2A receptors is low (pK_i 7.73). Cariprazine may have a lower risk of side effects associated with histamine H₁ and 5-HT_2C receptors due to its moderate or low affinity for these receptors (pK_i 7.63 and 6.87, respectively)[2]. The inhibition of isoproterenol-induced cAMP production in HEK-293 cells by capriprazine (EC50=1.4 nM) is more than six times that of apiriprazole (EC50=9.2 nM)[4].

ln Vivo

Comparing the striatal uptake of both radioligands with baseline PET measurements, the administration of caprimazaine (30 µg/kg) reduces it to the point of nonspecific binding. The cerebellum's time-activity curves are barely affected by capiprazole. Both the agonist radioligand [¹¹C]MNPA and the antagonist [¹¹C] raclopride exhibit dose-dependent dopamine D₂/D₃ receptor occupancy of approximately 80% and 45%, respectively, at doses of 30 µg/kg and 5.0 µg/kg. Dopamine D₂/D₃ receptor receptor occupancy, as determined by the MRTM2 and transient equilibrium methods, varied from 5% at the lowest dose (1.0 µg/kg) to 94% at the highest dose (300 µg/kg)[1]. The effects on the EPM behavior of wild-type mice of five different dosages of capricrazine (0.005 to 0.15 mg/kg) are investigated. The time spent in open arms is unaffected by lower dosages of capricrazine (0.005 to 0.02 mg/kg), but it is significantly decreased by the two higher doses (0.08 and 0.15 mg/kg) (ANOVA, (F(5,52)=4.20; p=0.0032)). Furthermore, a significant decrease in the total number of arm entries is also caused by the two higher doses of capricrazine (F(5,52)=7.21; p=0.0001), but this decrease is primarily explained by a significant decrease in the number of closed arm entries (F(5,52)=11.75; p=0.0001)). The EPM test shows that the two highest doses of capriprazine, 0.08 and 0.15 mg/kg, significantly impact locomotor activity. However, doses between 0.005 and 0.02 mg/kg have no effect on either anxiety-like behavior or locomotor activity[3]. When acute i.p. administration of all doses of capriprazine (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) is administered, compared with ouabain injection alone (114.6±14.33), a significant (P<0.01) reduction in ouabain-induced hyperactivity is observed. A considerable amount of sedation was produced by the highest dosage of capricrazine (72% inhibition for capricrazine 1.0 mg/kg aCSF vs. saline aCSF; P<0.05)[4].

Enzyme Assay

These tests are conducted in the following solutions: 50 mM Tris (pH 7.4), 100 mM NaCl, 7 mM MgCl₂, 1 mM EDTA, and 1 mM DTT. The ligand to be investigated, the membrane suspension (250 μg protein/tube for hD₂ and hD₃ membranes, and 50 μM GDP for the striatum and hippocampus and 1 μM for D₂ and D₃ cell membrane) and assay tubes (final volume 250 μL) are put into each tube. 30°C is used for a 10-minute preincubation period. Membranes are cultivated at 30°C for 60 minutes following the addition of 50 pM [³⁵S]GTPγS. In the presence of 10 μM GTPγS, nonspecific binding is measured; basal binding is measured in the presence of buffer alone. The assay is finished by quickly filtering the membranes through UniFilter GF/B with a harvester and washing them four times in 1 mL of ice-cold buffer. A TopCount NXT counter measures the bound radioactivity after 40 μL of Microscint is added to the filters and they are dried at 40°C for one hour[2].

Cell Assay

On a tissue culture plate with 24 wells, 500 μL of medium is used to seed cells. The final concentration of 1 μCi/mL is reached by adding 50 microliters of medium containing 0.55 μCi myo-[3H]inositol, and the mixture is incubated for 18–20 hours. After that, cells are passed through three rounds of washing in a buffer that has the following concentrations: 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). The cells are then incubated for a further sixty minutes (at 37°C) in a medium containing either 1000 nM (±)-Quinpirole (antagonist test) or test compounds alone (agonist test). The medium is then removed by aspiration, 400 μL of 0.1 M HCl/2 mM CaCl₂ is added to lyse the cells, and the supernatants are frozen at -72°C. Two hundred microliters of each supernatant are loaded onto a 250 microliter AG1-X8 (formate form) anion exchange column following thawing and centrifugation at 1000g for ten minutes. Two rounds of column washing in 1.5 mL of distilled water follow the disposal of the effluent. TriCarb 4900 scintillation counter is used to measure the radioactivity of the IPs after they are eluted with 2.5 mL of 1 M ammonium formate/0.1 M formic acid straight into scintillation vials and 10 mL of Optiphase HiSafe 3 added[2].

Animal Protocol

Mice: Mice of the C57Bl/6J wild type are used in the experiments. Using drug concentrations that do not affect emotional behavior or impair locomotor activity is crucial when testing cognitive functions. The behavior of mice in the EPM, a test of anxiety-related behavior that is also critically dependent upon normal locomotor activity, was affected by the administration of capracrazine (administered at a dose range of 0.005 to 0.15 mg/kg). An EPM apparatus made for mice is presented to the animals (leg height: 45 cm, arm length: 35 cm, lane width: 5 cm, wall height: 15 cm). Testing takes place between 1 and 4 PM in lighting with less than 100 lux. Mice are positioned in the middle of the maze, and during a five-minute test period, the amount of time they spend in open arms and the total number of closed and open arm entries are noted. Anxiety-like behavior was measured by counting the number of open arms entries and the amount of time spent in open arms. The locomotor activity was measured by counting the number of closed arm entries.
Rats: Sprague-Dawley adult male rats weighing 150–300 g are utilized. Before injecting ouabain intraperitoneally (i.c.v.) one hour prior, capiprazine is dissolved in 0.9% saline and given intraperitoneally (i.p.) at 0.06, 0.25, 0.5, and 1.0 mg/kg every day for seven days. After the intravenous injection, open field activity is measured both immediately after and seven days later (the activity is recorded 10–14 hours after the final intraperitoneal injection of capricrazine).

References

[1]. Occupancy of dopamine D2 and D3 and serotonin 5-HT1A receptors by the novel antipsychotic drug candidate, cariprazine (RGH-188), in monkey brain measured using positron emission tomography. Psychopharmacology (Berl). 2011 Dec;218(3):579-8.

[2]. Cariprazine (RGH-188), a dopamine D(3) receptor-preferring, D(3)/D(2) dopamine receptor antagonist-partial agonist antipsychotic candidate: in vitro and neurochemical profile. J Pharmacol Exp Ther. 2010 Apr;333(1):328-40.

[3]. Cariprazine, a dopamine D(3)-receptor-preferring partial agonist, blocks phencyclidine-induced impairments of working memory, attention set-shifting, and recognition memory in the mouse. Psychopharmacology (Berl). 2013 Mar;226(1):91-100.

[4]. Cariprazine exerts antimanic properties and interferes with dopamine D2 receptor β-arrestin interactions. Pharmacol Res Perspect. 2015 Feb;3(1):e00073

[5]. Cariprazine in schizophrenia: clinical efficacy, tolerability, and place in therapy. Adv Ther. 2013 Feb;30(2):114-26.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C21H33CL3N4O
Molecular Weight	463.87
Exact Mass	426.2
Elemental Analysis	C, 54.38; H, 7.17; Cl, 22.93; N, 12.08; O, 3.45
CAS #	1083076-69-0
Related CAS #	Cariprazine; 839712-12-8
Appearance	Solid powder
SMILES	CN(C)C(=O)NC1CCC(CC1)CCN2CCN(CC2)C3=C(C(=CC=C3)Cl)Cl.Cl
InChi Key	GPPJWWMREQHLQT-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H32Cl2N4O.ClH/c1-25(2)21(28)24-17-8-6-16(7-9-17)10-11-26-12-14-27(15-13-26)19-5-3-4-18(22)20(19)23;/h3-5,16-17H,6-15H2,1-2H3,(H,24,28);1H
Chemical Name	3-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-1,1-dimethylurea;hydrochloride
Synonyms	MP-214 HCl; MP 214 HCl; RGH188 HCl; RGH 188 HCl; MP214 HCl; GH-188 HCl; Cariprazine; trade name: Vraylar
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)

Solubility Data

Solubility (In Vitro)

DMSO: 6.7~12 mg/mL (14.4~25.9 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 0.67 mg/mL (1.44 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 6.7 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: ≥ 0.67 mg/mL (1.44 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 6.7 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.

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Solubility in Formulation 3: ≥ 0.67 mg/mL (1.44 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 6.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

Solubility in Formulation 4: 5%DMSO + 40%PEG300 + 5%Tween 80 + 50%ddH2O: 0.6mg/ml (1.29mM)

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1558 mL	10.7789 mL	21.5578 mL
	5 mM	0.4312 mL	2.1558 mL	4.3116 mL
	10 mM	0.2156 mL	1.0779 mL	2.1558 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
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The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

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The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
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Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

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Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

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Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05368558	Recruiting	Drug: Cariprazine Drug: Placebo	Schizophrenia	AbbVie	August 18, 2022	Phase 3
NCT05913947	Recruiting	Drug: Lithium Drug: Cariprazine	Depression, Bipolar	Aalborg University Hospital	December 13, 2022	Phase 4
NCT04777357	Recruiting	Drug: Cariprazine Drug: Placebo	Depression Bipolar I Disorder	AbbVie	April 28, 2021	Phase 3
NCT05439616	Recruiting	Drug: Cariprazine Drug: Placebo	Autism Spectrum Disorder	AbbVie	July 7, 2022	Phase 3
NCT04771299	Recruiting	Drug: Cariprazine Drug: Placebo	Bipolar I Disorder Cognitive Impairment	Jayasree Basivireddy	July 7, 2021	Phase 3

Biological Data

Open field activity immediately after injection with ouabain Acute administration of cariprazine inhibits ICV ouabain-induced motoric hyperactivity in rats. Pharmacol Res Perspect . 2015 Feb;3(1):e00073.

The effect of cariprazine on the behavior of mice exposure to the EPM. Psychopharmacology (Berl) . 2013 Mar;226(1):91-100.

The effect of cariprazine on PCP-induced impairment of social interaction (T1) and social recognition memory (T2; T1-T2) in wild-type and D3-receptor knockout mice. Psychopharmacology (Berl) . 2013 Mar;226(1):91-100.