Tiotixene

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Tiotixene
Thiothixene.svg
Clinical data
Trade names Navane
Synonyms Thiothixene (USAN US)
AHFS/Drugs.com Monograph
MedlinePlus a682867
Pregnancy
category
Routes of
administration
By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolism Hepatic
Elimination half-life 10–20 hours
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEMBL
ECHA InfoCard 100.024.547 Edit this at Wikidata
Chemical and physical data
Formula C23H29N3O2S2
Molar mass 443.627 g/mol
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]

Pharmacology[edit]

Pharmacodynamics[edit]

Tiotixene[3]
Site Ki (nM) Species Ref
SERT 3,162–3,878 Human [3][4]
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[edit]

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

Chemistry[edit]

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

References[edit]

  1. ^ http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm
  2. ^ José Miguel Vela; Helmut Buschmann; Jörg Holenz; Antonio Párraga; Antoni Torrens (2007). Antidepressants, Antipsychotics, Anxiolytics: From Chemistry and Pharmacology to Clinical Application. Weinheim: Wiley-VCH. p. 520. ISBN 3-527-31058-4. 
  3. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai Roth, BL; Driscol, J. "PDSP Ki Database" (HTML). Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017. 
  4. ^ a b c d e f g h i j k l m n o p q r s Silvestre JS, Prous J (2005). "Research on adverse drug events. I. Muscarinic M3 receptor binding affinity could predict the risk of antipsychotics to induce type 2 diabetes". Methods Find Exp Clin Pharmacol. 27 (5): 289–304. doi:10.1358/mf.2005.27.5.908643. PMID 16082416. 
  5. ^ a b c d e f g h i j k l Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, Jayathilake K, Meltzer HY, Roth BL (2003). "H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs". Neuropsychopharmacology. 28 (3): 519–26. doi:10.1038/sj.npp.1300027. PMID 12629531. 
  6. ^ a b c Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, Nash NR, Olsson R, Davis RE, Hacksell U, Weiner DM, Brann MR (2005). "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". J. Pharmacol. Exp. Ther. 315 (3): 1278–87. doi:10.1124/jpet.105.092155. PMID 16135699. 
  7. ^ Kanba S, Richelson E (1984). "Histamine H1 receptors in human brain labelled with [3H]doxepin". Brain Res. 304 (1): 1–7. 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. 
  9. ^ Edward Shorter (2009). Before Prozac: The Troubled History of Mood Disorders in Psychiatry. Oxford University Press, USA. pp. 51–. ISBN 978-0-19-536874-1.