Triazoledione (developmental code name BMS-180492) is a phenylpiperazine compound and a major metabolite of the antidepressant nefazodone.[1] [2] 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.
| Site | Ki (nM) | Species | Ref | |
|---|---|---|---|---|
| ≥34,527 ≥26,471 | Human Rat | |||
| >100,000 100,000 | Human Rat | |||
| 636–1,371 | Rat | |||
| 159–211 | Rat | |||
| 173 1,000 | Human Rat | |||
| 1,915 1,000 | Human Rat | |||
| >100,000 | Rat | |||
| 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.
| Compound | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 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 | ||
| 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. | ||||||||||