Flufenazin

Flufenazin
(IUPAC) ime
	2-[4-[3-[2-(trifluorometil)-10H-fenotiazin-10-il]propil]piperazin-1-il]etanol
Klinički podaci
AHFS/Drugs.com	Monografija
MedlinePlus	a682172
Identifikatori
CAS broj	69-23-8
ATC kod	N05AB02
PubChem	3372
DrugBank	DB00623
ChemSpider	3255
UNII	S79426A41Z
KEGG	D07977
ChEBI	CHEBI:5123
ChEMBL	CHEMBL726
Hemijski podaci
Formula	C22H26F3N3OS
Mol. masa	437,523 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C22H26F3N3OS/c23-22(24,25)17-6-7-21-19(16-17)28(18-4-1-2-5-20(18)30-21)9-3-8-26-10-12-27(13-11-26)14-15-29/h1-2,4-7,16,29H,3,8-15H2 ; Key: PLDUPXSUYLZYBN-UHFFFAOYSA-N
Farmakokinetički podaci
Bioraspoloživost	40% - 50%
Metabolizam	Hepatički
Poluvreme eliminacije	15 do 30 sata
Izlučivanje	žuč/izmet
Farmakoinformacioni podaci
Trudnoća	C(US)
Pravni status	℞ Prescription only
Način primene	oralno, IM

Flufenazin je tipični antipsihotik koji se koristi za tretman psihoza kao što su šizofrenija, manična faza bipolarnog poremećaja, agitacija, i demencija. On pripada piperazinskoj klasi fenotiazina. Mehanizam dejstva leka nije potpuno poznat. Ovaj lek može da pomogne u kontroli simptoma tako što blokira ili umanjuje dejstvo dopamina na mozak. Nivo dopamina može da bude povišen kod ljudi obolelih od šizofrenije i drugih psihoza.

Nuspojave ovog leka su slične sa haloperidolom, naime predominantno proizvodi efekte blokiranja dopamina, te može da dođe do akatizije, parkinsonizma, i tremora. Dugotrajne nuspojave uključuju potencijalno nepovratnu tardivnu diskineziju i potencijalno fatalni neuroleptički maligni sindrom.

Hemija

Flufenazin (4-[3-[2-(trifluorometil)fenotiazin-10-il]propil]-1-piperazinetanol) se sintetiše koji su slični pripremi trifluoperazina i srodnih antipsihotika.^[6]^[7]^[8]^[9]^[10]^[11]^[12]

Alkilacijom 2-trifluorometilfenotiazina koristeći 4-formil-1-piperazinilpropilhlorid u prisustvu natrijum amida formira se 2-trifluorometil-10-[3-(4-formil-1-piperazinil)propil]fenotiazin. Dalja alkalna hidroliza uklanja N-formil grupu, dajući 2-trifluorometil-10-[3-(1-piperazinil)propil]fenotiazin. On se alkiluje 2-bromoetanol-1 acetatom, i nakon dalje kisele hidrolize uklanja se zaštitna acetilna grupa, dajući flufenazin.^[12]^[13]

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
↑ G.E. Ullyot, U.S. Patent 3.058.979 (1962).
↑ R.C. Merril, H.L. Yale, U.S. Patent 3.394.131 (1963).
↑ Smith Kline & French Lab., GB 829246 (1960).
↑ Sherico Ltd., GB 833474 (1960).
↑ R.C. Merril, H.L. Yale, U.S. Patent 3.194.733 (1965).
↑ Yale, Harry L.; Sowinski, Francis (1960). „43-[10-(2-Trifluoromethyl)-phenothiazinyl]-propyl1-piperazine-ethanol1 and Related Compounds. II2”. Journal of the American Chemical Society 82: 2039. DOI:10.1021/ja01493a047.
↑ ^12,0 ^12,1 E.L. Anderson, G.B. Bellizona, P.N. Craig, G.E. Jaffe, K.P. Janewaes, C. Kaiser, B.M. Hester, E.J. Nikawitz, A. Pavloff, H.E. Reift, Ch.L. Zirkle, Arzneim.-Forsch., 12, 937 (1962).
↑ J.W. Cusic, U.S. Patent 2.766.235 (1956).

Spoljašnje veze

"Fluphenazine". Davis's Drug Guide for Nurses, Eighth Edition. F.A. Davis Company, 2005. ISBN 0-8036-2455-7.
Fluphenazine Dichlorhydrate Arhivirano 2012-05-31 na Wayback Machine-u [Article in French] Biam Last Updated: 11 December 2000. Accessed 14 September 2005.

[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] G.E. Ullyot, U.S. Patent 3.058.979 (1962).

[7] R.C. Merril, H.L. Yale, U.S. Patent 3.394.131 (1963).

[8] Smith Kline & French Lab., GB 829246 (1960).

[9] Sherico Ltd., GB 833474 (1960).

[10] R.C. Merril, H.L. Yale, U.S. Patent 3.194.733 (1965).

[11] Yale, Harry L.; Sowinski, Francis (1960). „43-[10-(2-Trifluoromethyl)-phenothiazinyl]-propyl1-piperazine-ethanol1 and Related Compounds. II2”. Journal of the American Chemical Society 82: 2039. DOI:10.1021/ja01493a047.

[E.L._Anderson,_G.B._Bellizona_1962-12] 12,0 ^12,1 E.L. Anderson, G.B. Bellizona, P.N. Craig, G.E. Jaffe, K.P. Janewaes, C. Kaiser, B.M. Hester, E.J. Nikawitz, A. Pavloff, H.E. Reift, Ch.L. Zirkle, Arzneim.-Forsch., 12, 937 (1962).

[13] J.W. Cusic, U.S. Patent 2.766.235 (1956).

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