Triazoledione

Triazoledione
Clinical data
Synonyms BMS-180492
Pharmacokinetic data
Elimination half-life 18 hours[1]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
Formula C23H28ClN5O3
Molar mass 457.96 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

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
α1 173
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.
  2. 1 2 3 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. 1 2 3 4 5 6 7 8 9 10 11 12 13 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. 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. 1 2 3 4 5 6 7 8 9 10 11 12 13 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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