Triazoledione

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]

Triazoledione
Clinical data
Other namesBMS-180492
Pharmacokinetic data
Elimination half-life18 hours[1]
Identifiers
IUPAC name
  • 1-[3-[4-(3-Chlorophenyl)piperazin-1-yl]propyl]-4-(2-phenoxyethyl)-1,2,4-triazolidine-3,5-dione
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC23H28ClN5O3
Molar mass457.96 g·mol−1
3D model (JSmol)
SMILES
  • C1CN(CCN1CCCN2C(=O)N(C(=O)N2)CCOC3=CC=CC=C3)C4=CC(=CC=C4)Cl
InChI
  • InChI=1S/C23H28ClN5O3/c24-19-6-4-7-20(18-19)27-14-12-26(13-15-27)10-5-11-29-23(31)28(22(30)25-29)16-17-32-21-8-2-1-3-9-21/h1-4,6-9,18H,5,10-17H2,(H,25,30)
  • Key:BTNXVMLCKOPOEP-UHFFFAOYSA-N

Pharmacology
Triazoledione[4][5][3]
SiteKi (nM)SpeciesRef
SERT≥34,527
≥26,471		Human
Rat		[5]
[5][3]
NET>100,000
100,000		Human
Rat		[5]
DATNDNDND
5-HT1A636–1,371Rat[3][5]
5-HT2A159–211Rat[5][3]
5-HT2CNDNDND
α1173
1,000		Human
Rat		[5]
[3]
α21,915
1,000		Human
Rat		[5]
[3]
β>100,000Rat[3]
H111Guinea pig[5]
mACh>100,000Rat[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]
Compound5-HT1A5-HT2ASERTNETα1α2βH1mACh
Hydroxynefazodone56–5897.2–34165–1,203376–1,0538.0–14563–2,490>1,0002811,357
mCPP16–411110–433127–432490–4,36097–763112–3714,8904494,702
Nefazodone52–1,0307.1–32181–549200–7135.5–14484–41,700>100,000304,569
Trazodone42–28811–20115–690≥20,88712–23106–1,07047,1002912,188
Triazoledione636–1,371159–211≥26,471>100,000≥173≥1,915>100,00011>100,000
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

See also

References
  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.{{cite book}}: CS1 maint: multiple names: authors list (link)
  2. 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. 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". 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. 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.



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