Triazoledione

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Triazoledione
Triazoledione.svg
Clinical data
SynonymsBMS-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[edit]

Triazoledione[4][5][3]
Site Ki (nM) Species Ref
SERT ≥34,527
≥26,471
Human
Rat
[5]
[5][3]
NET >100,000
100,000
Human
Rat
[5]
DAT ND ND ND
5-HT1A 636–1,371 Rat [3][5]
5-HT2A 159–211 Rat [5][3]
5-HT2C ND ND ND
α1 173
1,000
Human
Rat
[5]
[3]
α2 1,915
1,000
Human
Rat
[5]
[3]
β >100,000 Rat [3]
H1 11 Guinea pig [5]
mACh >100,000 Rat [5]
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][5] It shows negligible affinity for the serotonin and norepinephrine transporters and the muscarinic acetylcholine receptors.[3][5]

Comparison of binding profiles of triazoledione and related compounds[3][5]
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[edit]

References[edit]

  1. ^ Alan F. Schatzberg, M.D.; Charles B. Nemeroff, M.D., Ph.D. (2017). The American Psychiatric Association Publishing Textbook of Psychopharmacology, Fifth Edition. American Psychiatric Pub. pp. 460–. ISBN 978-1-58562-523-9.CS1 maint: Multiple names: authors list (link)
  2. ^ a b c Sheldon H. Preskorn; Christina Y. Stanga; John P. Feighner; Ruth Ross (6 December 2012). Antidepressants: Past, Present and Future. Springer Science & Business Media. pp. 68–. ISBN 978-3-642-18500-7.
  3. ^ a b c d e f g h i j k l m Davis R, Whittington R, Bryson HM (1997). "Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression". Drugs. 53 (4): 608–36. doi:10.2165/00003495-199753040-00006. PMID 9098663.
  4. ^ 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.
  5. ^ a b c d e f g h i j k l m Owens MJ, Morgan WN, Plott SJ, Nemeroff CB (1997). "Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites". J. Pharmacol. Exp. Ther. 283 (3): 1305–22. PMID 9400006.