Chemistry:Triazoledione

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Short description: Phenylpiperazine compound
Triazoledione
Triazoledione.svg
Clinical data
Other namesBMS-180492
Pharmacokinetic data
Elimination half-life18 hours[1]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC23H28ClN5O3
Molar mass457.96 g·mol−1
3D model (JSmol)

Triazoledione (developmental code name BMS-180492) is a phenylpiperazine compound and a major metabolite of the antidepressant nefazodone.[2][3] It is active, but with substantially reduced potency compared to nefazodone (approximately one-seventh).[3][2] As such, it has been suggested that it is unlikely that triazoledione contributes significantly to the pharmacology of nefazodone.[3] However, triazoledione may reach concentrations as great as 10 times those of nefazodone, and hence could still be a significant contributor to its therapeutic effects.[2]

Pharmacology

Site Ki (nM) Species Ref
SERT ≥34,527
≥26,471		 Human
Rat		 [4]
[4][3]
NET >100,000
100,000		 Human
Rat		 [4]
DAT ND ND ND
5-HT1A 636–1,371 Rat [3][4]
5-HT2A 159–211 Rat [4][3]
5-HT2C ND ND ND
α1 173
1,000		 Human
Rat		 [4]
[3]
α2 1,915
1,000		 Human
Rat		 [4]
[3]
β >100,000 Rat [3]
H1 11 Guinea pig [4]
mACh >100,000 Rat [4]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Triazoledione shows significant affinity for the serotonin 5-HT1A and 5-HT2A receptors, the α1-adrenergic receptor, and the histamine H1 receptor.[3][4] It shows negligible affinity for the serotonin and norepinephrine transporters and the muscarinic acetylcholine receptors.[3][4]

Comparison of binding profiles of triazoledione and related compounds[3][4]
Compound 5-HT1A 5-HT2A SERT NET α1 α2 β H1 mACh
Hydroxynefazodone 56–589 7.2–34 165–1,203 376–1,053 8.0–145 63–2,490 >1,000 28 11,357
mCPP 16–411 110–433 127–432 490–4,360 97–763 112–371 4,890 449 4,702
Nefazodone 52–1,030 7.1–32 181–549 200–713 5.5–144 84–41,700 >100,000 30 4,569
Trazodone 42–288 11–20 115–690 ≥20,887 12–23 106–1,070 47,100 29 12,188
Triazoledione 636–1,371 159–211 ≥26,471 >100,000 ≥173 ≥1,915 >100,000 11 >100,000
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

See also

References

  1. ↑ "Trazodone and Nefazodone". The American Psychiatric Association Publishing Textbook of Psychopharmacology (Fifth ed.). American Psychiatric Pub. 2017. pp. 460–. ISBN 978-1-58562-523-9. https://books.google.com/books?id=KfHEDgAAQBAJ&pg=PA460. 
  2. ↑ 2.0 2.1 2.2 "General Principles of Pharmacokinetics". Antidepressants: Past, Present and Future. Springer Science & Business Media. 6 December 2012. pp. 68–. ISBN 978-3-642-18500-7. https://books.google.com/books?id=Ue3uCAAAQBAJ&pg=PA68. 
  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 "Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression". Drugs 53 (4): 608–636. April 1997. doi:10.2165/00003495-199753040-00006. PMID 9098663. 
  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 Cite error: Invalid <ref> tag; no text was provided for refs named pmid9400006



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