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Triazoledione

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Phenylpiperazine compound Pharmaceutical compound
Triazoledione
Clinical data
Other namesBMS-180492
Pharmacokinetic data
Elimination half-life18 hours
Identifiers
IUPAC name
  • 1-propyl]-4-(2-phenoxyethyl)-1,2,4-triazolidine-3,5-dione
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H28ClN5O3
Molar mass457.96 g·mol
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

Triazoledione (developmental code name BMS-180492) is a phenylpiperazine compound and a major metabolite of the antidepressant nefazodone. It is active, but with substantially reduced potency compared to nefazodone (approximately one-seventh). As such, it has been suggested that it is unlikely that triazoledione contributes significantly to the pharmacology of nefazodone. 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.

Pharmacology

Triazoledione
Site Ki (nM) Species Ref
SERTTooltip Serotonin transporter ≥34,527
≥26,471		 Human
Rat
NETTooltip Norepinephrine transporter >100,000
100,000		 Human
Rat
DATTooltip Dopamine transporter ND ND ND
5-HT1A 636–1,371 Rat
5-HT2A 159–211 Rat
5-HT2C ND ND ND
α1 173
1,000		 Human
Rat
α2 1,915
1,000		 Human
Rat
β >100,000 Rat
H1 11 Guinea pig
mAChTooltip Muscarinic acetylcholine receptor >100,000 Rat
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. It shows negligible affinity for the serotonin and norepinephrine transporters and the muscarinic acetylcholine receptors.

Comparison of binding profiles of triazoledione and related compounds
Compound 5-HT1A 5-HT2A SERTTooltip Serotonin transporter NETTooltip Norepinephrine transporter α1 α2 β H1 mAChTooltip Muscarinic acetylcholine receptor
Hydroxynefazodone 56–589 7.2–34 165–1,203 376–1,053 8.0–145 63–2,490 >1,000 28 11,357
mCPPTooltip meta-Chlorophenylpiperazine 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. Golden RN, Dawkins K, Nicholas L (2017). "Trazodone and Nefazodone". In Schatzberg AF, Nemeroff CB (eds.). The American Psychiatric Association Publishing Textbook of Psychopharmacology (Fifth ed.). American Psychiatric Pub. pp. 460–. ISBN 978-1-58562-523-9.
  2. ^ Preskorn SH, Catterson ML (6 December 2012). "General Principles of Pharmacokinetics". In Preskorn SH, Stanga CY, Feighner JP, Ross R (eds.). Antidepressants: Past, Present and Future. Springer Science & Business Media. pp. 68–. ISBN 978-3-642-18500-7.
  3. ^ Davis R, Whittington R, Bryson HM (April 1997). "Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression". Drugs. 53 (4): 608–636. doi:10.2165/00003495-199753040-00006. PMID 9098663. S2CID 239077479.
  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 (December 1997). "Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites". The Journal of Pharmacology and Experimental Therapeutics. 283 (3): 1305–1322. PMID 9400006.
Pharmacodynamics
Adrenergic receptor modulators
α1
Agonists
Antagonists
α2
Agonists
Antagonists
β
Agonists
Antagonists
Histamine receptor modulators
H1
Agonists
Antagonists
H2
Agonists
Antagonists
H3
Agonists
Antagonists
H4
Agonists
Antagonists
See also
Receptor/signaling modulators
Monoamine metabolism modulators
Monoamine reuptake inhibitors
Serotonin receptor modulators
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT3–7
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
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