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 names	BMS-180492
Pharmacokinetic data
Elimination half-life	18 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	153707-88-1
PubChem CID	9804174
ChemSpider	7979934
UNII	3508097W2U
ChEMBL	ChEMBL1598729
CompTox Dashboard (EPA)	DTXSID701122505
Chemical and physical data
Formula	C23H28ClN5O3
Molar mass	457.96 g·mol−1
3D model (JSmol)	Interactive image
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]

Site	Ki (nM)	Species	Ref
SERTTooltip Serotonin transporter	≥34,527 ≥26,471	Human Rat	[5] [5][3]
NETTooltip Norepinephrine transporter	>100,000 100,000	Human Rat	[5]
DATTooltip Dopamine transporter	ND	ND	ND
5-HT1A	636–1,371	Rat	[3][5]
5-HT2A	159–211	Rat	[5][3]
5-HT2C	ND	ND	ND
α1	173 1,000	Human Rat	[5] [3]
α2	1,915 1,000	Human Rat	[5] [3]
β	>100,000	Rat	[3]
H1	11	Guinea pig	[5]
mAChTooltip Muscarinic acetylcholine receptor	>100,000	Rat	[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-HT_1A and 5-HT_2A 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]

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

• Serotonin antagonist and reuptake inhibitor