Aripiprazol

Aripiprazol
(IUPAC) ime
	74-[4-(2,3-dihlorofenil)piperazin-1-il]butoksi3,4-dihidrohinolin-2(1H)-on
Klinički podaci
Robne marke	Abilify
AHFS/Drugs.com	Monografija
MedlinePlus	a603012
Identifikatori
CAS broj	129722-12-9
ATC kod	N05AX12
PubChem	60795
DrugBank	DB01238
ChemSpider	54790
UNII	82VFR53I78
KEGG	D01164
ChEBI	CHEBI:31236
ChEMBL	CHEMBL1112
Hemijski podaci
Formula	C23H27Cl2N3O2
Mol. masa	448,385
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C23H27Cl2N3O2/c24-19-4-3-5-21(23(19)25)28-13-11-27(12-14-28)10-1-2-15-30-18-8-6-17-7-9-22(29)26-20(17)16-18/h3-6,8,16H,1-2,7,9-15H2,(H,26,29) ; Key: CEUORZQYGODEFX-UHFFFAOYSA-N
Farmakokinetički podaci
Bioraspoloživost	87%
Vezivanje za proteine plazme	>99%
Metabolizam	liver
Poluvreme eliminacije	75 h (aktivni metabolit: 94 h)
Izlučivanje	fekalije i urin
Farmakoinformacioni podaci
Licenca	EU EMEA:link, US FDA:link
Trudnoća	?
Pravni status	℞ Prescription only
Način primene	oralno; intramuskularno

Aripiprazol (Abilify, Aripipreks) je atipični antipsihotik i antidepresant, koji se koristi za lečenje šizofrenije, manično-depresivne psihoze i kliničke depresije. FDA je odobrila upotrebu ovog leka za lečenje šizofrenije 15. novembra 2002; za primenu kod akutnih maničnih i mešovitih epizoda 1 oktobra 1, 2004; kao dodatnu terapiju za kliničku depresiju 20. novembra 2007; i za lečenje iritabilnosti kod dece sa autizmom 20. novembra 2009.^[6]^[7] Aripiprazol je razvila kompanija Otsuka u Japanu i SAD-u.

Farmakologija

Aripiprazol poseduje afinitet za i deluje na sledećim receptorima i transporterima:

D2 parcijalni agonist
D4 receptori
5-HT1A parcijalni agonist
5-HT2A antagonist
5-HT2C parcijalni agonist
5-HT7 antagonist
Histamin (umereni afinitet)
α-adrenergic

Mehanizam dejstva aripiprazola se razlikuje drugih odobrenih atipičnih antipsihotika (npr., klozapina, olanzapina, kvetiapina, ziprazidona, i risperidona). Umesto da antagonizuje D₂ receptor, aripiprazol deluje D₂ parcijalni agonist (K_i = 0,34 nM).^[8]^[9] Aripiprazol je takođe parcijalni agonist na 5-HT_1A receptoru (K_i = 1,65 nM), i poput drugih atipičnih antipsihotika manifestuje profil antagonista na 5-HT_2A receptoru (K_i = 0,8 nM).^[10]^[11] On isto tako antagonizuje 5-HT₇ receptor (K_i = 39 nM) i deluje kao parcijalni agonist na 5-HT_2C receptoru (K_i = 15 nM). Ovo zadnje dejstvo je mogući uzrok minimalnog uvećanja telesne težine tokom terapije.^[12] Aripiprazol ima umeren afinitet za histaminski (K_i = 61 nM), α-adrenergiki (K_i = 57 nM) i D4 receptore, kao i za serotoninski transporter. On nema afinitet za holinergičke muskarinske receptore.^[13]

Izvori

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948863. edit
↑ Hitti, Miranda (20 November 2007). „FDA OKs Abilify for Depression”. WebMD. Pristupljeno 8. 12. 2008.
↑ Keating, Gina (23 November 2009). „FDA OKs Abilify for child autism irritability”. Reuters. Pristupljeno 22. 9. 2010.
↑ Lawler CP et al. (1999). „Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes”. Neuropsychopharmacology 20 (6): 612–27. DOI:10.1016/S0893-133X(98)00099-2. PMID 10327430.
↑ Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, Nash NR, Olsson R, Davis RE, Hacksell U, Weiner DM, Brann MR (December 2005). „Intrinsic Efficacy of Antipsychotics at Human D₂, D₃, and D₄ Dopamine Receptors: Identification of the Clozapine Metabolite N-Desmethylclozapine as a D₂/D₃ Partial Agonist”. J Pharmacol Exp Ther 315 (3): 1278–87. DOI:10.1124/jpet.105.092155. PMID 16135699.
↑ Jordan, S et al. (2002). „The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor”. Eur J Pharmacol 441 (3): 137–140. DOI:10.1016/S0014-2999(02)01532-7. PMID 12063084.
↑ Shapiro, DA et al. (2003). „Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology”. Neuropsychopharmacology 28 (8): 1400–1411. DOI:10.1038/sj.npp.1300203. PMID 12784105.
↑ Zhang JY, Kowal DM, Nawoschik SP, Lou Z, Dunlop J (February 2006). „Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms”. Biochem Pharmacol 71 (4): 521–9. DOI:10.1016/j.bcp.2005.11.007. PMID 16336943.
↑ „Abilify (Aripiprazole) - Clinical Pharmacology”. DrugLib.com. 14. 2. 2007.. Arhivirano iz originala na datum 2008-05-22. Pristupljeno 8. 12. 2008.

Vanjske veze

Abilify
Informacije o propisivanju leka Arhivirano 2010-03-31 na Wayback Machine-u

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.

[5] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948863. edit

[6] Hitti, Miranda (20 November 2007). „FDA OKs Abilify for Depression”. WebMD. Pristupljeno 8. 12. 2008.

[7] Keating, Gina (23 November 2009). „FDA OKs Abilify for child autism irritability”. Reuters. Pristupljeno 22. 9. 2010.

[lawler-8] Lawler CP et al. (1999). „Interactions of the novel antipsychotic aripiprazole (OPC-14597) with dopamine and serotonin receptor subtypes”. Neuropsychopharmacology 20 (6): 612–27. DOI:10.1016/S0893-133X(98)00099-2. PMID 10327430.

[burstein-9] Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, Nash NR, Olsson R, Davis RE, Hacksell U, Weiner DM, Brann MR (December 2005). „Intrinsic Efficacy of Antipsychotics at Human D₂, D₃, and D₄ Dopamine Receptors: Identification of the Clozapine Metabolite N-Desmethylclozapine as a D₂/D₃ Partial Agonist”. J Pharmacol Exp Ther 315 (3): 1278–87. DOI:10.1124/jpet.105.092155. PMID 16135699.

[jordan-10] Jordan, S et al. (2002). „The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor”. Eur J Pharmacol 441 (3): 137–140. DOI:10.1016/S0014-2999(02)01532-7. PMID 12063084.

[shapiro-11] Shapiro, DA et al. (2003). „Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology”. Neuropsychopharmacology 28 (8): 1400–1411. DOI:10.1038/sj.npp.1300203. PMID 12784105.

[pmid16336943-12] Zhang JY, Kowal DM, Nawoschik SP, Lou Z, Dunlop J (February 2006). „Distinct functional profiles of aripiprazole and olanzapine at RNA edited human 5-HT2C receptor isoforms”. Biochem Pharmacol 71 (4): 521–9. DOI:10.1016/j.bcp.2005.11.007. PMID 16336943.

[drugLabelPC-13] „Abilify (Aripiprazole) - Clinical Pharmacology”. DrugLib.com. 14. 2. 2007.. Arhivirano iz originala na datum 2008-05-22. Pristupljeno 8. 12. 2008.

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