Tiotixene
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)[1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
MetabolismHepatic
Elimination half-life10–20 hours
Identifiers
  • (9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]-9H-thioxanthene-2-sulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.233.356 Edit this at Wikidata
Chemical and physical data
FormulaC23H29N3O2S2
Molar mass443.62 g·mol−1
3D model (JSmol)
  • O=S(=O)(N(C)C)c2cc1C(\c3c(Sc1cc2)cccc3)=C/CCN4CCN(C)CC4
  • InChI=1S/C23H29N3O2S2/c1-24(2)30(27,28)18-10-11-23-21(17-18)19(20-7-4-5-9-22(20)29-23)8-6-12-26-15-13-25(3)14-16-26/h4-5,7-11,17H,6,12-16H2,1-3H3/b19-8- checkY
  • Key:GFBKORZTTCHDGY-UWVJOHFNSA-N checkY
  (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[2] by Pfizer.[3]

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

Pharmacology

Pharmacodynamics

See also: Antipsychotic § Mechanism of action, and Antipsychotic § Comparison of medications

Tiotixene[4]
Site Ki (nM) Species Ref
SERTTooltip Serotonin transporter 3,162–3,878 Human [4][5]
NETTooltip Norepinephrine transporter 30,200 Human [4][5]
DATTooltip Dopamine transporter 3,630 Human [4][5]
5-HT1A 410–912 Human [4][6][5]
5-HT1B 151 Human [4]
5-HT1D 659 Human [4]
5-HT1E >10,000 Human [4]
5-HT2A 50–89 Human [6][5]
5-HT2C 1,350–1,400 Human [6][5]
5-HT3 1,860 Human [4][5]
5-HT5A 361 Human [4]
5-HT6 208–320 Human [4][6][5]
5-HT7 15.5 Human [4][6][5]
α1 19 ND [5]
  α1A 11–12 Human [4][6]
  α1B 35 Human [4]
α2 95 ND [5]
  α2A 80 Human [4][6]
  α2B 50 Human [4][6]
  α2C 52 Human [4][6]
β1 >10,000 Human [4]
β2 >10,000 Human [4]
D1 51–339 Human [4][5]
D2 0.03–1.4 Human [4][6][7]
D3 0.3–186 Human [7][5]
D4 203–363 Human [4][5]
D4.2 410–685 Human [7]
D5 261 Human [4]
H1 4.0–12 Human [4][6][8]
H2 411 Human [4]
H3 1,336 Guinea pig [4]
H4 >10,000 Human [4]
mAChTooltip Muscarinic acetylcholine receptor 3,310 ND [5]
  M1 ≥2,820 Human [4][5]
  M2 ≥2,450 Human [4][5]
  M3 ≥5,750 Human [4][6][5]
  M4 >10,000 Human [4]
  M5 5,376 Human [4]
σ 1,780 ND [5]
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).[4] 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).[4] It does not have any anticholinergic activity.[4] Antagonism of the D2 receptor is thought to be responsible for the antipsychotic effects of tiotixene.

History

Tiotixene was introduced in 1967.[9][10]

Chemistry

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

References

  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. Retrieved 2023-08-16.
  2. ^ "Drugs@FDA: FDA-Approved Drugs".
  3. ^ Vela JM, Buschmann H, Holenz J, Párraga A, Torrens A (2007). Antidepressants, Antipsychotics, Anxiolytics: From Chemistry and Pharmacology to Clinical Application. Weinheim: Wiley-VCH. p. 520. ISBN 978-3-527-31058-6.
  4. ^ 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". 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.
  5. ^ a b c d e f g h i j k l m n o p q r s Silvestre JS, Prous J (June 2005). "Research on adverse drug events. I. Muscarinic M3 receptor binding affinity could predict the risk of antipsychotics to induce type 2 diabetes". Methods and Findings in Experimental and Clinical Pharmacology. 27 (5): 289–304. doi:10.1358/mf.2005.27.5.908643. PMID 16082416.
  6. ^ a b c d e f g h i j k l Kroeze WK, Hufeisen SJ, Popadak BA, Renock SM, Steinberg S, Ernsberger P, et al. (March 2003). "H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs". Neuropsychopharmacology. 28 (3): 519–526. doi:10.1038/sj.npp.1300027. PMID 12629531.
  7. ^ a b c Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, et al. (December 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". The Journal of Pharmacology and Experimental Therapeutics. 315 (3): 1278–1287. doi:10.1124/jpet.105.092155. PMID 16135699. S2CID 2247093.
  8. ^ Kanba S, Richelson E (June 1984). "Histamine H1 receptors in human brain labelled with [3H]doxepin". Brain Research. 304 (1): 1–7. doi:10.1016/0006-8993(84)90856-4. PMID 6146381. S2CID 45303586.
  9. ^ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia. Elsevier. pp. 3214–. ISBN 978-0-8155-1856-3.
  10. ^ Shorter E (2009). Before Prozac: The Troubled History of Mood Disorders in Psychiatry. Oxford University Press, USA. pp. 51–. ISBN 978-0-19-536874-1.