Cariprazinum
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Cave: notitiae huius paginae nec praescriptiones nec consilia medica sunt. |
| 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
[recensere | fontem recensere]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
[recensere | fontem recensere]Natura chemica
[recensere | fontem recensere]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
[recensere | fontem recensere]Cariprazinum est medicamentum cum virtutibus antipsychoticis et antidepressivis. Codex ATC est N05AX15 (WHO).
Pharmacodynamica
[recensere | fontem recensere]Cariprazinum potissime receptoria dopamini D3, paulo minus receptoria D2 obsidet[5].
| Receptorium | Cariprazini affinitas ligandi, Ki (nM)[6] | Actio |
|---|---|---|
| dopamini D2L | 0.49 | agonista partialis |
| dopamini D2S | 0.69 | agonista partialis |
| dopamini D3 | 0.085 | agonista partialis |
| serotonini 5-HT1A | 2.6 | agonista partialis |
| serotonini 5-HT2A | 18.8 | antagonista |
| serotonini 5-HT2B | 0.58 | antagonista |
| serotonini 5-HT2C | 134 | agonista inversa |
| serotonini 5-HT7 | 111 | antagonista |
| adrenergicum α1A | 155 | antagonista |
| histamini H1 | 23.2 | antagonista |
| muscarinicum acetylcholini | > 1,000 | antagonista |
Pharmacocinetica
[recensere | fontem recensere]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
[recensere | fontem recensere]Cytochromatis CYP3A4 ope in duo gradus primo DCAR deinde DDCAR oriuntur.
Effectus Cariprazini
[recensere | fontem recensere]In schizophrenia Cariprazinum effectus sympatomum negativorum deminuat[8].
Notae
[recensere | fontem recensere]- ↑ 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
[recensere | fontem recensere]- Situs interretialis fabricatoris Cariprazini (divulgationibus) (Anglice)