Cariprazinum

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**Cariprazinum**
Cognitores
ChemSpider	25999972
PubChem	11154555
DrugBank	DB06016
Natura chemica


Formula chemica	C ₂₁H ₃₂Cl ₂N ₄O
Massa molaris	427.411 g/mol
Natura pharmacologica
Codex ATC	N05AX15 (WHO)
Semivita biologica	2-5 d desmethyl~: 2-3 hebd.
Metabolismus	iecore (hepaticus): CYP3A4
Metaboliti	Desmethylo- Cariprazinum (DCAR) Didesmethylo-Cariprazinum (DDCAR)
Excretio	renibus (21%), faecibus
Ad usum therapeuticum
Applicatio	per os

Cariprazinum est substantia antipsychotica, agonista dopamini partialis (D₃ > D₂), ad schizophreniam tractandam^[1]. In senectute periculum apoplexiae cerebri auctum est. Neque valor prolactini auctus neque intervallum QT prolongatum observantur.

Historia

Ante annum 2008 grex Hungaricus societatis Richter Gedeon Nyrt. varias substantias receptoria dopamini D₃ et minus D₂ inhibentes investigavit^[2]. Paulo post sub nomen Cariprazini pristinum RGH-188 inventum erat^[3] et anno 2012 Cariprazinum praesentatum est^[4].

Natura Cariprazini

Natura chemica

Cariprazinum est piperazinum. Nomen chemicum (IUPAC) est 3-[4-[2-[4-(2,3-dichloro-phenyl)-piperazino-1-yl]-aethyl]-cyclohexyl]-1,1-dimethyl-urea. Massa molaris est 427.411 g/mol.

Natura pharmacologica

Cariprazinum est medicamentum cum virtutibus antipsychoticis et antidepressivis. Codex ATC est N05AX15 (WHO).

Pharmacodynamica

Cariprazinum potissime receptoria dopamini D₃, paulo minus receptoria D₂ obsidet^[5].

Receptorium	Cariprazini affinitas ligandi, K_i (nM)^[6]	Actio
dopamini D_2L	0.49	agonista partialis
dopamini D_2S	0.69	agonista partialis
dopamini D₃	0.085	agonista partialis
serotonini 5-HT_1A	2.6	agonista partialis
serotonini 5-HT_2A	18.8	antagonista
serotonini 5-HT_2B	0.58	antagonista
serotonini 5-HT_2C	134	agonista inversa
serotonini 5-HT₇	111	antagonista
adrenergicum α_1A	155	antagonista
histamini H₁	23.2	antagonista
muscarinicum acetylcholini	> 1,000	antagonista

Pharmacocinetica

Tempus semivitae biologicum Cariprazini est duo dies usque ad quinque dies. Cariprazinum substratum Cytochromatis P450 CYP3A4 (minus CYP2D6) est.
Metaboliti sunt Desmethylo-Cariprazinum (DCAR) et Di-Desmethylo-Cariprazinum (DDCAR)^[7]. Tempora semivitae biologica metabolitorum Cariprazino magis longiora sunt, ita Desmethylo-Cariprazino 2-3 hebdomades est.

Metaboliti

Cytochromatis CYP3A4 ope in duo gradus primo DCAR deinde DDCAR oriuntur.

Effectus Cariprazini

In schizophrenia Cariprazinum effectus sympatomum negativorum deminuat^[8].

Notae

↑ Ceskova E., Silhan P. (2018). "Novel treatment options in depression and psychosis". Neuropsychiatr Dis Treat 14: 741-7
↑ Kiss B., Laszlovszky I., Horváth A., Némethy Z., Schmidt E., Bugovics G., Fazekas K., Gyertyán I., Agai-Csongor E., Domány G., Szombathelyi Z. (2008). "Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: I. neurochemical characterisation of RG-15". Naunyn Schmiedebergs Arch Pharmacol 378 (5): 515-28
↑ Mészáros G. P., Agai-Csongor E., Kapás M. (2008). "Sensitive LC-MS/MS methods for the quantification of RGH-188 and its active metabolites, desmethyl- and didesmethyl-RGH-188 in human plasma and urine". J Pharm Biomed Anal 48 (2): 388-97
↑ Agai-Csongor E., Domány G., Nógrádi K., Galambos J., Vágó I., Keserű G. M., Greiner I., Laszlovszky I., Gere A., Schmidt E., Kiss B., Vastag M., Tihanyi K., Sághy K., Laszy J., Gyertyán I., Zájer-Balázs M., Gémesi L., Kapás M., Szombathelyi Z. (2012). "Discovery of cariprazine (RGH-188): a novel antipsychotic acting on dopamine D3/D2 receptors". Bioorg Med Chem Lett 22 (10): 3437-40
↑ 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. (2010). "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 333 (1): 328-40
↑ https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php
↑ Nakamura T., Kubota ., Iwakaji A., Imada M., Kapás M., Morio Y. (2016). "Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week Treatment)". Drug design, development and treatment 10: 327-38
↑ Németh G., Laszlovszky I. (Mar 2017). "Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial". Lancet 389 (10074): 1103-13

Nexus interni

Aripiprazolum - (D₂ > D₃ antagonista partialis)
Receptorium dopamini D2
Receptorium dopamini D3

Nexus externi

Situs interretialis fabricatoris Cariprazini (divulgationibus) (Anglice)

[1] Ceskova E., Silhan P. (2018). "Novel treatment options in depression and psychosis". Neuropsychiatr Dis Treat 14: 741-7

[2] Kiss B., Laszlovszky I., Horváth A., Némethy Z., Schmidt E., Bugovics G., Fazekas K., Gyertyán I., Agai-Csongor E., Domány G., Szombathelyi Z. (2008). "Subnanomolar dopamine D3 receptor antagonism coupled to moderate D2 affinity results in favourable antipsychotic-like activity in rodent models: I. neurochemical characterisation of RG-15". Naunyn Schmiedebergs Arch Pharmacol 378 (5): 515-28

[3] Mészáros G. P., Agai-Csongor E., Kapás M. (2008). "Sensitive LC-MS/MS methods for the quantification of RGH-188 and its active metabolites, desmethyl- and didesmethyl-RGH-188 in human plasma and urine". J Pharm Biomed Anal 48 (2): 388-97

[4] Agai-Csongor E., Domány G., Nógrádi K., Galambos J., Vágó I., Keserű G. M., Greiner I., Laszlovszky I., Gere A., Schmidt E., Kiss B., Vastag M., Tihanyi K., Sághy K., Laszy J., Gyertyán I., Zájer-Balázs M., Gémesi L., Kapás M., Szombathelyi Z. (2012). "Discovery of cariprazine (RGH-188): a novel antipsychotic acting on dopamine D3/D2 receptors". Bioorg Med Chem Lett 22 (10): 3437-40

[KISS-5] 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. (2010). "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 333 (1): 328-40

[6] ttps://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php

[7] Nakamura T., Kubota ., Iwakaji A., Imada M., Kapás M., Morio Y. (2016). "Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week Treatment)". Drug design, development and treatment 10: 327-38

[8] Németh G., Laszlovszky I. (Mar 2017). "Cariprazine versus risperidone monotherapy for treatment of predominant negative symptoms in patients with schizophrenia: a randomised, double-blind, controlled trial". Lancet 389 (10074): 1103-13

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