Chemistry:Tiotixene

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Short description: Typical antipsychotic medication


Tiotixene
Thiothixene.svg
Clinical data
Trade namesNavane
Other namesThiothixene (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa682867
Pregnancy
category
  • AU: B1
Routes of
administration		By mouth
Drug classTypical antipsychotic
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • BR: Class C1 (Other controlled substances)
  • In general: ℞ (Prescription only)
Pharmacokinetic data
MetabolismHepatic
Elimination half-life10–20 hours
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC23H29N3O2S2
Molar mass443.62 g·mol−1
3D model (JSmol)
  (verify)

Tiotixene, or thiothixene, sold under the brand name Navane among others, is a typical antipsychotic of the thioxanthene class which is related to chlorprothixene and is used in the treatment of psychoses like schizophrenia and bipolar mania. It was introduced in the United States in 1967[1] by Pfizer.[2]

Tiotixene is also related to thioproperazine and pipotiazine, members of the phenothiazine class.

Pharmacology

Pharmacodynamics

Site Ki (nM) Species Ref
NET 30,200 Human [3][4]
DAT 3,630 Human [3][4]
5-HT1A 410–912 Human [3][5][4]
5-HT1B 151 Human [3]
5-HT1D 659 Human [3]
5-HT1E >10,000 Human [3]
5-HT2A 50–89 Human [5][4]
5-HT2C 1,350–1,400 Human [5][4]
5-HT3 1,860 Human [3][4]
5-HT5A 361 Human [3]
5-HT6 208–320 Human [3][5][4]
5-HT7 15.5 Human [3][5][4]
α1 19 ND [4]
  α1A 11–12 Human [3][5]
  α1B 35 Human [3]
α2 95 ND [4]
  α2A 80 Human [3][5]
  α2B 50 Human [3][5]
  α2C 52 Human [3][5]
β1 >10,000 Human [3]
β2 >10,000 Human [3]
D1 51–339 Human [3][4]
D2 0.03–1.4 Human [3][5][6]
D3 0.3–186 Human [6][4]
D4 203–363 Human [3][4]
D4.2 410–685 Human [6]
D5 261 Human [3]
H1 4.0–12 Human [3][5][7]
H2 411 Human [3]
H3 1,336 Guinea pig [3]
H4 >10,000 Human [3]
mACh 3,310 ND [4]
  M1 ≥2,820 Human [3][4]
  M2 ≥2,450 Human [3][4]
  M3 ≥5,750 Human [3][5][4]
  M4 >10,000 Human [3]
  M5 5,376 Human [3]
σ 1,780 ND [4]
Values are Ki (nM). The smaller the value,
the more strongly the drug binds to the site.

Tiotixene acts primarily as a highly potent antagonist of the dopamine D2 and D3 receptors (subnanomolar affinity).[3] It is also an antagonist of the histamine H1, α1-adrenergic, and serotonin 5-HT7 receptors (low nanomolar affinity), as well as of various other receptors to a much lesser extent (lower affinity).[3] It does not have any anticholinergic activity.[3] Antagonism of the D2 receptor is thought to be responsible for the antipsychotic effects of tiotixene.

History

Tiotixene was introduced in 1967.[8][9]

Chemistry

Tiotixene is a member of the thioxanthene class of antipsychotics. Analogues include chlorprothixene, clopenthixol, flupentixol, and zuclopenthixol.

References

  1. ↑ "Drugs@FDA: FDA-Approved Drugs". http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. 
  2. ↑ Antidepressants, Antipsychotics, Anxiolytics: From Chemistry and Pharmacology to Clinical Application. Weinheim: Wiley-VCH. 2007. p. 520. ISBN 978-3-527-31058-6. https://books.google.com/books?id=yXD4QA-Y_Z0C&pg=PA520. 
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 3.22 3.23 3.24 3.25 3.26 3.27 3.28 3.29 3.30 3.31 3.32 Cite error: Invalid <ref> tag; no text was provided for refs named PDSP
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 Cite error: Invalid <ref> tag; no text was provided for refs named pmid16082416
  5. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 5.11 "H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs". Neuropsychopharmacology 28 (3): 519–526. March 2003. doi:10.1038/sj.npp.1300027. PMID 12629531. 
  6. ↑ 6.0 6.1 6.2 "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". The Journal of Pharmacology and Experimental Therapeutics 315 (3): 1278–1287. December 2005. doi:10.1124/jpet.105.092155. PMID 16135699. 
  7. ↑ "Histamine H1 receptors in human brain labelled with [3H]doxepin". Brain Research 304 (1): 1–7. June 1984. doi:10.1016/0006-8993(84)90856-4. PMID 6146381. 
  8. ↑ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia. Elsevier. pp. 3214–. ISBN 978-0-8155-1856-3. https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA3214. 
  9. ↑ Before Prozac: The Troubled History of Mood Disorders in Psychiatry. Oxford University Press, USA. 2009. pp. 51–. ISBN 978-0-19-536874-1. https://books.google.com/books?id=nCtnDAAAQBAJ&pg=PA51. 



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