Ziprasidon

Ziprasidon
(IUPAC) ime
	5-{2-[4-(1,2-benzizotiazol-3-il)-1-piperazinil]etil}-; 6-hloro-1,3-dihidro-2H-indol-2-on
Klinički podaci
Robne marke	Geodon
AHFS/Drugs.com	Monografija
MedlinePlus	a699062
Identifikatori
CAS broj	146939-27-7
ATC kod	N05AE04
PubChem	60854
DrugBank	DB00246
ChemSpider	54841
UNII	6UKA5VEJ6X
KEGG	D08687
ChEBI	CHEBI:10119
ChEMBL	CHEMBL708
Hemijski podaci
Formula	C21H21ClN4OS
Mol. masa	412,936
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C21H21ClN4OS/c22-17-13-18-15(12-20(27)23-18)11-14(17)5-6-25-7-9-26(10-8-25)21-16-3-1-2-4-19(16)28-24-21/h1-4,11,13H,5-10,12H2,(H,23,27) ; Key: MVWVFYHBGMAFLY-UHFFFAOYSA-N
Farmakokinetički podaci
Bioraspoloživost	100% (intramuskularno); 60% (oralno)
Metabolizam	hepatički (aldehid reduktaza)
Poluvreme eliminacije	7 sati
Izlučivanje	Urin i fekalije
Farmakoinformacioni podaci
Licenca	US FDA:link
Trudnoća	C(US)
Pravni status	℞ Prescription only
Način primene	oralno, intramuskularno

Ziprasidon (Geodon, Zeldoks) je atipični antipsihotik. FDA je odobrila ovaj lek februara 2001 za lečenje šizofrenije. U obliku intramuskularne injekcije ziprasidon je odobren za akutnu agitaciju šizofreničnih pacijenata. Ziprasidon je isto tako odobren za akutni tretman manije i mešovitih psihijatrijskih stanja vezanih za manično-depresivnu psihozu.^[6]^[7]

Farmakologija

Ziprasidon poseduje afinitet za i deluje na sledećim receptorima i transporterima:^[8]

D₂ antagonist (K_i = 4.8 nM)
D₃ antagonist (K_i = 7.2 nM)
5-HT_1A agonist (K_i = 3.4 nM)
5-HT_1D antagonist (K_i = 2.3 nM)
5-HT_2A antagonist/inverzni agonist (K_i = 0.4 nM)
5-HT_2C (K_i = 1.3 nM)
NET
SERT
H₁ Antagonist (K_i = 47 nM)
α₁-adrenergic Antagonist (K_i = 10 nM)
mACh (IC₅₀ >1000 nM) [neznatan afinitet]

Ziprasidon ima visok afinitet za dopaminske, serotoninske, i alfa adrenergičke receptore i umereni afinitet ha histaminske receptore. Smatra se da deluje kao antagonist na tim receptorima.^[8]^[9] Ziprasidon takođe pokazuje umerenu inhibiciju sinaptičkog ponovnog preuzimanja serotonina i norepinefrina,^[8]^[9]^[10] mada je klinički značaj toga nepoznat.

Mehanizam dejstva ziprasidona je nije razjašnjen. Pretpostavlja se da je njegovo antipsihotičko dejstvo prvenstveno posredovano antagonizmon na dopaminskim receptorima, specifično D₂ podtipu. Serotoninski antagonizam takođe može da ima ulogu u efektivnosti ziprasidona, mada je značaj 5-HT_2A antagonizma predmet debata među naučnicima.^[11] Zipratidon je verovatno najselektivniji za 5-HT_2A receptore u odnosu na D₂ i 5-HT_2C receptore među neurolepticima.^[12]^[13] Antagonizam na histaminskim i alfa adrenergičkim receptorima je verovatan razlog za neke od nuspojava ziprasidona, poput sedacije i ortostaze.

Reference

↑ 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 21948594. edit
↑ Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred (2006). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11 izd.). New York: McGraw-Hill. ISBN 0-07-142280-3.
↑ Pdr Staff (2009). PDR: Physicians Desk Reference 2010 (Physicians' Desk Reference (Pdr)). Rozelle, N.S.W: Thomson Reuters. ISBN 1-56363-748-0.
↑ ^8,0 ^8,1 ^8,2 „Ziprasidone full prescribing information”. Arhivirano iz originala na datum 2011-12-24. Pristupljeno 2013-06-03.
↑ ^9,0 ^9,1 Nemeroff CB, Lieberman JA, Weiden PJ, Harvey PD, Newcomer JW, Schatzberg AF, Kilts CD, Daniel DG. (November 2005). „From clinical research to clinical practice: a 4-year review of ziprasidone”. CNS Spectr 10 (11 Suppl 17): 1–20. PMID 16381088.
↑ Tatsumi M, Jansen K, Blakely RD, Richelson E (March 1999). „Pharmacological profile of neuroleptics at human monoamine transporters”. Eur J Pharmacol 368 (2–3): 277–283. DOI:10.1016/S0014-2999(99)00005-9. PMID 10193665.
↑ Lüllmann, Heinz; Lutz Hein, Klaus Mohr (2006). Pharmakologie und Toxikologie. Thieme Medical Publishers. ISBN 978-3-13-368516-0.
↑ Marek GJ, Carpenter LL, McDougle CJ, Price LH (2003). „Synergistic action of 5-HT_2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders”. Neuropsychopharmacology 28 (2): 402–12. DOI:10.1038/sj.npp.1300057. PMID 12589395.
↑ Seeger TF, Seymour PA, Schmidt AW, Zorn SH, Schulz DW, Lebel LA, McLean S, Guanowsky V, Howard HR, Lowe JA (October 1995). „Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity”. J Pharmacol Exp Ther 275 (1): 101–13. PMID 7562537.

Literatura

David Taylor (2006), „Ziprasidone”, Schizophrenia in focus, ISBN 9780853696070

Spoljašnje veze

[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 21948594. edit

[6] Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred (2006). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11 izd.). New York: McGraw-Hill. ISBN 0-07-142280-3.

[7] Pdr Staff (2009). PDR: Physicians Desk Reference 2010 (Physicians' Desk Reference (Pdr)). Rozelle, N.S.W: Thomson Reuters. ISBN 1-56363-748-0.

[geodon-8] 8,0 ^8,1 ^8,2 „Ziprasidone full prescribing information”. Arhivirano iz originala na datum 2011-12-24. Pristupljeno 2013-06-03.

[nemeroff-9] 9,0 ^9,1 Nemeroff CB, Lieberman JA, Weiden PJ, Harvey PD, Newcomer JW, Schatzberg AF, Kilts CD, Daniel DG. (November 2005). „From clinical research to clinical practice: a 4-year review of ziprasidone”. CNS Spectr 10 (11 Suppl 17): 1–20. PMID 16381088.

[tatsumi-10] Tatsumi M, Jansen K, Blakely RD, Richelson E (March 1999). „Pharmacological profile of neuroleptics at human monoamine transporters”. Eur J Pharmacol 368 (2–3): 277–283. DOI:10.1016/S0014-2999(99)00005-9. PMID 10193665.

[Pharmakologie-11] Lüllmann, Heinz; Lutz Hein, Klaus Mohr (2006). Pharmakologie und Toxikologie. Thieme Medical Publishers. ISBN 978-3-13-368516-0.

[pmid12589395-12] Marek GJ, Carpenter LL, McDougle CJ, Price LH (2003). „Synergistic action of 5-HT_2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders”. Neuropsychopharmacology 28 (2): 402–12. DOI:10.1038/sj.npp.1300057. PMID 12589395.

[seeger-13] Seeger TF, Seymour PA, Schmidt AW, Zorn SH, Schulz DW, Lebel LA, McLean S, Guanowsky V, Howard HR, Lowe JA (October 1995). „Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity”. J Pharmacol Exp Ther 275 (1): 101–13. PMID 7562537.

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