Triazoledione

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;
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;

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]
Site	K_i (nM)	Species	Ref
SERT	≥34,527 ≥26,471	Human Rat	[5] [5][3]
NET	>100,000 100,000	Human Rat	[5]
DAT	ND	ND	ND
5-HT_1A	636–1,371	Rat	[3][5]
5-HT_2A	159–211	Rat	[5][3]
5-HT_2C	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]
mACh	>100,000	Rat	[5]
Values are K_i (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-HT_1A	5-HT_2A	SERT	NET	α₁	α₂	β	H₁	mACh
Hydroxynefazodone	56–589	7.2–34	165–1,203	376–1,053	8.0–145	63–2,490	>1,000	28	11,357
mCPP	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 K_i (nM). The smaller the value, the more strongly the drug binds to the site.

References

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.CS1 maint: multiple names: authors list (link)
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.
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. doi:10.2165/00003495-199753040-00006. PMID 9098663.
Roth, BL; Driscol, J. "PDSP K_i 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.
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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[SchatzbergNemeroff2017-1] 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.CS1 maint: multiple names: authors list (link)

[PreskornStanga2012-2] 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.

[pmid9098663-3] 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. doi:10.2165/00003495-199753040-00006. PMID 9098663.

[PDSP-4] Roth, BL; Driscol, J. "PDSP K_i 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.

[pmid9400006-5] 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.

Triazoledione

Pharmacology

See also

References