Cariprazine free base | 839712-12-8 | antipsychotic

MedKoo Cat#: 330051 | Name: Cariprazine free base

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Cariprazine, also known as RGH-188 and MP-214, is an antipsychotic drug received FDA approval on September 17, 2015. Cariprazine acts as a D2 and D3 receptor partial agonist, with high selectivity towards the D3 receptor. Action on the dopaminergic systems makes it also potentially useful as an add-on therapy in major depressive disorder. Cariprazine is approved for schizophrenia and bipolar disorder. It has also been investigated as a potential adjunct in treatment-resistant major depressive disorder.

Chemical Structure

Cariprazine free base

CAS#839712-12-8 (free base)

Theoretical Analysis

MedKoo Cat#: 330051

Name: Cariprazine free base

CAS#: 839712-12-8 (free base)

Chemical Formula: C21H32Cl2N4O

Exact Mass: 426.1953

Molecular Weight: 427.41

Elemental Analysis: C, 59.01; H, 7.55; Cl, 16.59; N, 13.11; O, 3.74

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to Ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to Ship
100mg	USD 450.00	Ready to Ship
200mg	USD 750.00	Ready to ship
500mg	USD 1,350.00	Ready to ship
1g	USD 1,950.00	Ready to Ship
2g	USD 2,950.00	Ready to Ship

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Related CAS #

1083076-69-0 (HCl) 839712-12-8 (free base)

Synonym

Cariprazine free base; RGH-188; RGH188; RGH 188; MP-214; MP 214; MP214;

IUPAC/Chemical Name

3-((1r,4r)-4-(2-(4-(2,3-dichlorophenyl)piperazin-1-yl)ethyl)cyclohexyl)-1,1-dimethylurea

InChi Key

KPWSJANDNDDRMB-QAQDUYKDSA-N

InChi Code

InChI=1S/C21H32Cl2N4O/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)/t16-,17-

SMILES Code

O=C(N[C@H]1CC[C@H](CCN2CCN(C3=CC=CC(Cl)=C3Cl)CC2)CC1)N(C)C

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A25T02K21

QC Data

View QC data: current batch, Lot#A25T02K21

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Cariprazine is a novel antipsychotic drug candidate that exhibits high affinity for the D3 (Ki=0.085 nM) and D2 (Ki=0.49 nM) receptors, and moderate affinity for the 5-HT1A receptor (Ki=2.6 nM).

In vitro activity:

Cariprazine had lower affinity at human and rat hippocampal 5-HT(1A) receptors (pK(i) 8.59 and 8.34, respectively) and demonstrated low intrinsic efficacy. Cariprazine displayed low affinity at human 5-HT(2A) receptors (pK(i) 7.73). Moderate or low affinity for histamine H(1) and 5-HT(2C) receptors (pK(i) 7.63 and 6.87, respectively) suggest cariprazine's reduced propensity for adverse events related to these receptors. Cariprazine demonstrated different functional profiles at dopamine receptors depending on the assay system. It displayed D(2) and D(3) antagonism in [(35)S]GTPgammaS binding assays, but stimulated inositol phosphate (IP) production (pEC(50) 8.50, E(max) 30%) and antagonized (+/-)-quinpirole-induced IP accumulation (pK(b) 9.22) in murine cells expressing human D(2L) receptors. It had partial agonist activity (pEC(50) 8.58, E(max) 71%) by inhibiting cAMP accumulation in Chinese hamster ovary cells expressing human D(3) receptors and potently antagonized R(+)-2-dipropylamino-7-hydroxy-1,2,3,4-tetrahydronaphtalene HBr (7-OH-DPAT)-induced suppression of cAMP formation (pK(b) 9.57). In these functional assays, cariprazine showed similar (D(2)) or higher (D(3)) antagonist-partial agonist affinity and greater (3- to 10-fold) D(3) versus D(2) selectivity compared with aripiprazole. Reference: J Pharmacol Exp Ther. 2010 Apr;333(1):328-40. https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=20093397

In vivo activity:

Cariprazine was tested in vivo for antimanic-like activity, using the ouabain-induced hyperactivity model in rats. Cariprazine was more potent than aripiprazole in inhibiting isoproterenol-induced cAMP although both compounds showed similar maximum efficacy. In assays of D2R/β-arrestin 2-dependent interactions, cariprazine showed very weak partial agonist activity, unless the levels of receptor kinase were increased; as an antagonist it showed similar potency to haloperidol and ∼fivefold greater potency than aripiprazole. In an animal model of mania, cariprazine showed similar efficacy as lithium in attenuating the effects of ouabain-induced hyperactivity. In summary, the differential effects of cariprazine on D2R G protein and β-arrestin 2 mediators of signal transduction pathways could contribute to its potent antimanic-like activity. Reference: Pharmacol Res Perspect. 2015 Feb;3(1):e00073. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25692006/

Preparing Stock Solutions

The following data is based on the product molecular weight 427.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Kiss B, Horváth A, Némethy Z, Schmidt E, Laszlovszky I, Bugovics G, Fazekas K, Hornok K, Orosz S, Gyertyán I, Agai-Csongor E, Domány G, Tihanyi K, Adham N, Szombathelyi Z. 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. doi: 10.1124/jpet.109.160432. Epub 2010 Jan 21. PMID: 20093397. 2. Gao Y, Peterson S, Masri B, Hougland MT, Adham N, Gyertyán I, Kiss B, Caron MG, El-Mallakh RS. Cariprazine exerts antimanic properties and interferes with dopamine D2 receptor β-arrestin interactions. Pharmacol Res Perspect. 2015 Feb;3(1):e00073. doi: 10.1002/prp2.73. Epub 2014 Dec 2. PMID: 25692006; PMCID: PMC4317219.

In vivo protocol:

1. Gao Y, Peterson S, Masri B, Hougland MT, Adham N, Gyertyán I, Kiss B, Caron MG, El-Mallakh RS. Cariprazine exerts antimanic properties and interferes with dopamine D2 receptor β-arrestin interactions. Pharmacol Res Perspect. 2015 Feb;3(1):e00073. doi: 10.1002/prp2.73. Epub 2014 Dec 2. PMID: 25692006; PMCID: PMC4317219. 2. Zimnisky R, Chang G, Gyertyán I, Kiss B, Adham N, Schmauss C. 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. doi: 10.1007/s00213-012-2896-5. Epub 2012 Oct 19. PMID: 23079899; PMCID: PMC3572273.

1: Rolin D, Whelan J, Montano CB. Is it depression or is it bipolar depression? J Am Assoc Nurse Pract. 2020 Oct;32(10):703-713. doi: 10.1097/JXX.0000000000000499. PMID: 33017361. 2: Edinoff A, Ruoff MT, Ghaffar YT, Rezayev A, Jani D, Kaye AM, Cornett EM, Kaye AD, Viswanath O, Urits I. Cariprazine to Treat Schizophrenia and Bipolar Disorder in Adults. Psychopharmacol Bull. 2020 Sep 14;50(4):83-117. PMID: 33012874; PMCID: PMC7511151. 3: Fagiolini A, Alcalá JÁ, Aubel T, Bienkiewicz W, Bogren MMK, Gago J, Cerveri G, Colla M, Sanchez FC, Cuomo A, Helge F, Iacoponi E, Karlsson PA, Peddu P, Pettorruso M, Pereira HJR, Schölin JS, Vernaleken IB. Treating schizophrenia with cariprazine: from clinical research to clinical practice. Real world experiences and recommendations from an International Panel. Ann Gen Psychiatry. 2020 Sep 26;19:55. doi: 10.1186/s12991-020-00305-3. PMID: 32999683; PMCID: PMC7520022. 4: Dieci M, Trama A, Mansi G. Resolution of Citalopram Sexual Adverse Effects With Low Dose of Cariprazine: A Case Report. Clin Neuropharmacol. 2020 Sep/Oct;43(5):164-165. doi: 10.1097/WNF.0000000000000409. PMID: 32947429. 5: Yatham LN, Vieta E, McIntyre RS, Jain R, Patel M, Earley W. Broad Efficacy of Cariprazine on Depressive Symptoms in Bipolar Disorder and the Clinical Implications. Prim Care Companion CNS Disord. 2020 Sep 17;22(5):20m02611. doi: 10.4088/PCC.20m02611. PMID: 32942346. 6: Cernea S, Dima L, Correll CU, Manu P. Pharmacological Management of Glucose Dysregulation in Patients Treated with Second-Generation Antipsychotics. Drugs. 2020 Sep 15. doi: 10.1007/s40265-020-01393-x. Epub ahead of print. PMID: 32930957. 7: Vokó Z, Bitter I, Mersich B, Réthelyi J, Molnár A, Pitter JG, Götze Á, Horváth M, Kóczián K, Fonticoli L, Lelli F, Németh B. Using informative prior based on expert opinion in Bayesian estimation of the transition probability matrix in Markov modelling-an example from the cost-effectiveness analysis of the treatment of patients with predominantly negative symptoms of schizophrenia with cariprazine. Cost Eff Resour Alloc. 2020 Aug 27;18:28. doi: 10.1186/s12962-020-00224-w. PMID: 32874137; PMCID: PMC7457290. 8: Jimoh IJ, Sebe B, Balicza P, Fedor M, Pataky I, Rudas G, Gal A, Inczedy- Farkas G, Nemeth G, Molnar MJ. Wernicke-Korsakoff syndrome associated with mtDNA disease. Ther Adv Neurol Disord. 2020 Jul 30;13:1756286420938972. doi: 10.1177/1756286420938972. PMID: 32821290; PMCID: PMC7412926. 9: Roza TH, Santos Lopes SL, Passos IC. Cariprazine for acute mood episodes in bipolar disorder. Bipolar Disord. 2020 Aug 13. doi: 10.1111/bdi.12979. Epub ahead of print. PMID: 32790141. 10: Lumateperone (Caplyta) for schizophrenia. Med Lett Drugs Ther. 2020 Jul 27;62(1603):113-116. PMID: 32728011. 11: El Mansari M, Ebrahimzadeh M, Hamati R, Iro CM, Farkas B, Kiss B, Adham N, Blier P. Long-term administration of cariprazine increases locus coeruleus noradrenergic neurons activity and serotonin1A receptor neurotransmission in the hippocampus. J Psychopharmacol. 2020 Oct;34(10):1143-1154. doi: 10.1177/0269881120936891. Epub 2020 Jul 20. PMID: 32684081. 12: Orsolini L, De Berardis D, Volpe U. Up-to-date expert opinion on the safety of recently developed antipsychotics. Expert Opin Drug Saf. 2020 Aug;19(8):981-998. doi: 10.1080/14740338.2020.1795126. Epub 2020 Jul 21. PMID: 32657173. 13: Yalin N, Young AH. Pharmacological Treatment of Bipolar Depression: What are the Current and Emerging Options? Neuropsychiatr Dis Treat. 2020 Jun 9;16:1459-1472. doi: 10.2147/NDT.S245166. PMID: 32606699; PMCID: PMC7294105. 14: Grant JE, Chamberlain SR. Cariprazine treatment of borderline personality disorder: A case report. Psychiatry Clin Neurosci. 2020 Jun 26. doi: 10.1111/pcn.13094. Epub ahead of print. PMID: 32588527. 15: Genaro-Mattos TC, Anderson A, Allen LB, Tallman KA, Porter NA, Korade Z, Mirnics K. Maternal cariprazine exposure inhibits embryonic and postnatal brain cholesterol biosynthesis. Mol Psychiatry. 2020 Jun 5. doi: 10.1038/s41380-020-0801-x. Epub ahead of print. PMID: 32504050. 16: Molnar MJ, Jimoh IJ, Zeke H, Palásti Á, Fedor M. Early-Onset Schizophrenia With Predominantly Negative Symptoms: A Case Study of a Drug-Naive Female Patient Treated With Cariprazine. Front Pharmacol. 2020 Apr 23;11:477. doi: 10.3389/fphar.2020.00477. PMID: 32390838; PMCID: PMC7191004. 17: Bahji A, Ermacora D, Stephenson C, Hawken ER, Vazquez G. Comparative efficacy and tolerability of pharmacological treatments for the treatment of acute bipolar depression: A systematic review and network meta-analysis. J Affect Disord. 2020 May 15;269:154-184. doi: 10.1016/j.jad.2020.03.030. Epub 2020 Mar 20. PMID: 32339131. 18: Vita A, Ceraso A, Valsecchi P. Esperienze di switch a cariprazina in pazienti affetti da schizofrenia con ricorrenze. Riv Psichiatr. 2019 Nov- Dec;54(6):16-19. doi: 10.1708/3340.33098. PMID: 32310935. 19: Mencacci C, Cerveri G, Palazzo C, Gesi C, Salvi V. Esperienze di switch a cariprazina in pazienti affetti da schizofrenia con risposta parziale. Riv Psichiatr. 2019 Nov-Dec;54(6):11-15. doi: 10.1708/3340.33097. PMID: 32310934. 20: Amore M, Aguglia A. Esperienze di switch a cariprazina in pazienti schizofrenici con comparsa di effetti collaterali/comorbilità mediche. Riv Psichiatr. 2019 Nov-Dec;54(6):7-10. doi: 10.1708/3340.33096. PMID: 32310933.