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 ≥34,527≥26,471 HumanRat >100,000100,000 HumanRat 5-HT1A 636–1,371 Rat 5-HT2A 159–211 Rat 5-HT2C α1 1731,000 HumanRat α2 1,9151,000 HumanRat β >100,000 Rat H1 11 Guinea pig >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 α1 α2 β H1 Hydroxynefazodone 56–589 7.2–34 165–1,203 376–1,053 8.0–145 63–2,490 >1,000 28 11,357 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 Serotonin antagonist and reuptake inhibitor
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