Tioridazin

Tioridazin
(IUPAC) ime
	102-[(RS)-1-Metilpiperidin-2-il]etil; 2-metilsulfanilfenotiazin
Klinički podaci
AHFS/Drugs.com	Potrošačka informacije o leku
MedlinePlus	a682119
Identifikatori
CAS broj	50-52-2
ATC kod	N05AC02
PubChem	5452
DrugBank	DB00679
ChemSpider	5253
UNII	N3D6TG58NI
KEGG	D00373
ChEBI	CHEBI:9566
ChEMBL	CHEMBL479
Hemijski podaci
Formula	C21H26N2S2
Mol. masa	370,577
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C21H26N2S2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(24-2)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3 ; Key: KLBQZWRITKRQQV-UHFFFAOYSA-N
Farmakokinetički podaci
Bioraspoloživost	nepotpuna
Metabolizam	hepatički
Poluvreme eliminacije	7–13 sati (do 20 sati)
Izlučivanje	izmet
Farmakoinformacioni podaci
Trudnoća	?
Pravni status	RX-only lek, nije narkotick
Način primene	oralno (tablete, ponekad sirup)

Tioridazin (Melaril, Novoridazin, Tioril) je piperidinski tipični antipsihotik iz fenotiazinske grupe. On je ranije široko korišćen za treatman šizofrenije i psihoze. Zbog moguće kardiotoksičnosti i izazivanja retinopatije pri visokim dozama ovaj lek se retko koristi, osim kod pacijenata kod kojih drugi lekovi nisu efikasni, ili imaju kontraindikacije. Ozbiljna nuspojava ovog leka je potencijalno fatalni neuroleptički maligni sindrom. On deluje putem centralnog adrenergičkog i dopaminskog blokiranja. U manjoj meri ispoljava antiholinergičku aktivnost.

U starijim referencama, on se ponekad opisuje kao atipični,^[6] dok ga skorije reference uglavnom klasifikuju kao tipični antipsihotik,^[7] dok se termin „atipični“ obično rezerviše za agense koji pokazuju D4 selektivnost ili serotoninski antagonizam.

Hemija

Tioridazin, (±)-(10-[2-(1-metil-2-piperidil)etil]-2-(metiltio)fenotiazin) se sintetiše putem alkilacije 2-metiltiofenotiazina sa 2-(2-hloroetil)-1-metilpiperidinom.^[8]^[9]

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
↑ Robertson A, MacDonald C (July 1984). „Atypical neuroleptics clozapine and thioridazine enhance amphetamine-induced stereotypy”. Pharmacol. Biochem. Behav. 21 (1): 97–101. DOI:10.1016/0091-3057(84)90137-0. PMID 6540455.
↑ Ichikawa J, Dai J, O'Laughlin IA, Fowler WL, Meltzer HY (March 2002). „Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum”. Neuropsychopharmacology 26 (3): 325–39. DOI:10.1016/S0893-133X(01)00312-8. PMID 11850147.
↑ J. Renz, J.P. Bourquin, G. Gamboni, G. Schwarb, U.S. Patent 3.239.514 (1966).
↑ Bourquin, J.-P.; Schwarb, G.; Gamboni, G.; Fischer, R.; Ruesch, L.; Guldimann, S.; Theus, V.; Schenker, E. i dr.. (1958). „Synthesen auf dem Phenothiazin-Gebiet. 2. Mitteilung. N-substituierte Mercaptophenothiazin-Derivate”. Helvetica Chimica Acta 41: 1072. DOI:10.1002/hlca.19580410420.

Vanjske veze

PubChem Substance Summary: Thioridazine National Center for Biotechnology Information
Antipsychotic Mellaril Removed from Market Schizophrenia Daily News Blog.
U.S. National Library of Medicine: Drug Information Portal - Thioridazine

[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

[pmid6540455-6] Robertson A, MacDonald C (July 1984). „Atypical neuroleptics clozapine and thioridazine enhance amphetamine-induced stereotypy”. Pharmacol. Biochem. Behav. 21 (1): 97–101. DOI:10.1016/0091-3057(84)90137-0. PMID 6540455.

[pmid11850147-7] Ichikawa J, Dai J, O'Laughlin IA, Fowler WL, Meltzer HY (March 2002). „Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum”. Neuropsychopharmacology 26 (3): 325–39. DOI:10.1016/S0893-133X(01)00312-8. PMID 11850147.

[8] J. Renz, J.P. Bourquin, G. Gamboni, G. Schwarb, U.S. Patent 3.239.514 (1966).

[9] Bourquin, J.-P.; Schwarb, G.; Gamboni, G.; Fischer, R.; Ruesch, L.; Guldimann, S.; Theus, V.; Schenker, E. i dr.. (1958). „Synthesen auf dem Phenothiazin-Gebiet. 2. Mitteilung. N-substituierte Mercaptophenothiazin-Derivate”. Helvetica Chimica Acta 41: 1072. DOI:10.1002/hlca.19580410420.

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