Movatterモバイル変換


[0]ホーム

URL:


Jump to content
WikipediaThe Free Encyclopedia
Search

Zotepine

From Wikipedia, the free encyclopedia
Atypical antipsychotic medication

Pharmaceutical compound
Zotepine
Clinical data
Trade namesZoleptil
AHFS/Drugs.comInternational Drug Names
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances)[1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability7–13% (oral)[2]
MetabolismN-desmethylation to norzotepine (30-40%)[2]
Eliminationhalf-life13.7–15.9 hours, 12 hours (Norzotepine)[2]
Excretion17% (Urine)[2]
Identifiers
  • 2-(3-chlorobenzo[b][1]benzothiepin-5-yl)oxy-N,N-dimethylethanamine
CAS Number
PubChemCID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard(EPA)
ECHA InfoCard100.189.143Edit this at Wikidata
Chemical and physical data
FormulaC18H18ClNOS
Molar mass331.86 g·mol−1
3D model (JSmol)
  • Clc2cc1C(/OCCN(C)C)=C\c3c(Sc1cc2)cccc3
  • InChI=1S/C18H18ClNOS/c1-20(2)9-10-21-16-11-13-5-3-4-6-17(13)22-18-8-7-14(19)12-15(16)18/h3-8,11-12H,9-10H2,1-2H3 checkY
  • Key:HDOZVRUNCMBHFH-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Zotepine is anatypical antipsychoticdrug indicated for acute and chronicschizophrenia. It has been used inGermany since 1990 (although it has been discontinued in Germany) andJapan since 1982.

Zotepine is not approved for use in the United States, United Kingdom, Australia, Canada or New Zealand.[3]

Medical uses

[edit]

Zotepine's primary use is as a treatment for schizophrenia[4] although clinical trials have been conducted (with positive results) into its efficacy as an antimanic agent in patients with acute bipolar mania.[5][6][7] In a 2013 study in a comparison of 15 antipsychotic drugs in effectivity in treating schizophrenic symptoms, zotepine demonstrated medium-strong effectivity. Less effective thanclozapine, slightly less effective thanolanzapine andrisperidone, approximately as effective aspaliperidone, and slightly more effective thanhaloperidol,quetiapine, andaripiprazole.[8]

Side effects

[edit]
Common[2][4]
Unknown frequency[2][4]
Rare[2][4]

Pharmacology

[edit]

Pharmacodynamics

[edit]

The antipsychotic effect of zotepine is thought to be mediated throughantagonist activity atdopamine andserotonin receptors. Zotepine has a highaffinity for theD1 andD2 receptors. It also affects the5-HT2A,5-HT2C,5-HT6, and5-HT7 receptors.[10] In addition, its active metabolite, norzotepine, serves as a potentnorepinephrine reuptake inhibitor.[11]

Macromolecule (Receptor or transporter protein)Ki [nM][10]
SERT151
NET530
DAT3621
5-HT1A470.5
5-HT1B59.5
5-HT1D119
5-HT1E700
5-HT2A2.7
5-HT2C2.6
5-HT3472
5-HT5A29
5-HT66
5-HT712
α1A7
α1B5
α2A180
α2B5.35
α2C106
M118
M2140
M373
M477
M5260
D171
D225
D2S5.4
D2L11
D36.4
D418
D5248
H13.21
H2500
H41977

Synthesis

[edit]

The reaction of 2-chloroacetophenone with 4-chlorothiophenol gives athioether. This is treated withmorpholine and sulfur in aWillgerodt–Kindler reaction to give aphenylacetic acid derivative after acidhydrolysis of the amide intermediate. Cyclization of this compound in the presence ofpolyphosphoric acid forms thedibenzothiepin ring system of the drug. Theenol ether, zotepine, is produced when this is treated with the chloroethyl amine and potassium carbonate in methyl isobutyl ketone as solvent. Under these conditions, the undesired product of C-alkylation is minimised.[12][13][14]

Society and culture

[edit]

Brand names

[edit]

Brand names includeLosizopilon(JP),Lodopin(ID,JP),Nipolept(DE†),Setous(JP),Zoleptil(CZ,PT,TR,UK†),Zotewin(IN); where † indicates a formulation that has been discontinued.

See also

[edit]

References

[edit]
  1. ^Anvisa (2023-03-31)."RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese).Diário Oficial da União (published 2023-04-04).Archived from the original on 2023-08-03. Retrieved2023-08-16.
  2. ^abcdefgTruven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Jun 25]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  3. ^ab"Zotepine".Martindale: The Complete Drug Reference. Royal Pharmaceutical Society of Great Britain. 16 August 2013. Retrieved2 November 2013.
  4. ^abcdBritish National Formulary 58. British Medical Association and Royal Pharmaceutical Society of Great Britain; 2009.
  5. ^Chan HY, Jou SH, Juang YY, Chang CJ, Chen JJ, Chen CH, et al. (April 2010)."A single-blind, comparative study of zotepine versus haloperidol in combination with a mood stabilizer for patients with moderate-to-severe mania".Psychiatry and Clinical Neurosciences.64 (2):162–9.doi:10.1111/j.1440-1819.2010.02066.x.PMID 20447012.S2CID 27657241.
  6. ^Harada T, Otsuki S (1986). "Antimanic effect of zotepine".Clinical Therapeutics.8 (4):406–14.PMID 3089626.
  7. ^Amann B, Sterr A, Mergl R, Dittmann S, Seemüller F, Dobmeier M, et al. (October 2005). "Zotepine loading in acute and severely manic patients: a pilot study".Bipolar Disorders.7 (5):471–6.doi:10.1111/j.1399-5618.2005.00241.x.PMID 16176441.
  8. ^Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis".Lancet.382 (9896):951–62.doi:10.1016/S0140-6736(13)60733-3.PMID 23810019.S2CID 32085212.
  9. ^abcLeucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis".Lancet.382 (9896):951–62.doi:10.1016/S0140-6736(13)60733-3.PMID 23810019.S2CID 32085212.
  10. ^abNational Institute of Mental Health (12 January 2011)."PDSD Ki Database". Chapel Hill (NC): University of North Carolina. Archived fromthe original on November 8, 2013. Retrieved2 November 2013.
  11. ^Shobo M, Kondo Y, Yamada H, Mihara T, Yamamoto N, Katsuoka M, et al. (June 2010). "Norzotepine, a major metabolite of zotepine, exerts atypical antipsychotic-like and antidepressant-like actions through its potent inhibition of norepinephrine reuptake".The Journal of Pharmacology and Experimental Therapeutics.333 (3):772–81.doi:10.1124/jpet.110.166264.PMID 20223878.S2CID 185592.
  12. ^Ueda I, Sato Y, Maeno S, Umio S (October 1975)."The synthesis of 10-(4-methylpiperazino)dibenzo (b,f)thiepin and related compounds. Neurotropic and psychotropic agents".Chemical & Pharmaceutical Bulletin.23 (10):2223–2231.doi:10.1248/cpb.23.2223.PMID 1212752.
  13. ^Ueda I, Sato Y, Maeno S, Umio S (October 1978)."Synthesis and pharmacological properties of 8-chloro-10-(2-dimethylaminoethoxy)dibenzo[b,f]thiepin and related compounds. Neurotropic and psychotropic agents. III".Chemical & Pharmaceutical Bulletin.26 (10):3058–3070.doi:10.1248/cpb.26.3058.PMID 31984.
  14. ^"Zotepine".Pharmaceutical Substances. Thieme. Archived fromthe original on 2024-07-10. Retrieved2024-07-10.

Further reading

[edit]
Typical
Disputed
Atypical
Others
α1
Agonists
Antagonists
α2
Agonists
Antagonists
β
Agonists
Antagonists
D1-like
Agonists
PAMs
Antagonists
D2-like
Agonists
Antagonists
H1
Agonists
Antagonists
H2
Agonists
Antagonists
H3
Agonists
Antagonists
H4
Agonists
Antagonists
DATTooltip Dopamine transporter
(DRIsTooltip Dopamine reuptake inhibitors)
NETTooltip Norepinephrine transporter
(NRIsTooltip Norepinephrine reuptake inhibitors)
SERTTooltip Serotonin transporter
(SRIsTooltip Serotonin reuptake inhibitors)
VMATsTooltip Vesicular monoamine transporters
Others
mAChRsTooltip Muscarinic acetylcholine receptors
Agonists
Antagonists
Precursors
(andprodrugs)
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT37
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
Classes
Antidepressants
(Tricyclic antidepressants(TCAs))
Antihistamines
Antipsychotics
Anticonvulsants
Anticholinergics
Others
Retrieved from "https://en.wikipedia.org/w/index.php?title=Zotepine&oldid=1315587916"
Categories:
Hidden categories:

[8]ページ先頭

©2009-2025 Movatter.jp