Desmethylzopiclone

Desmethylzopiclone
Clinical data
Other names	SEP-174559
Identifiers
	IUPAC name [6-(5-chloropyridin-2-yl)-5-oxo-7H-pyrrolo[3,4-b]pyrazin-7-yl] piperazine-1-carboxylate;
CAS Number	59878-63-6;
PubChem CID	162892;
ChemSpider	143002;
UNII	DJL5TX7YTA;
CompTox Dashboard (EPA)	DTXSID10866775 ;
Chemical and physical data
Formula	C16H15ClN6O3
Molar mass	374.79 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CN(CCN1)C(=O)OC2C3=NC=CN=C3C(=O)N2C4=NC=C(C=C4)Cl;
	InChI InChI=InChI=1S/C16H15ClN6O3/c17-10-1-2-11(21-9-10)23-14(24)12-13(20-4-3-19-12)15(23)26-16(25)22-7-5-18-6-8-22/h1-4,9,15,18H,5-8H2; Key:CGSFZSTXVVJLIX-UHFFFAOYSA-N;

Desmethylzopiclone, also known as SEP-174559, is an active metabolite of the sedative-hypnotic drug zopiclone.

Pharmacology

Unlike its parent compound, which is a largely non-selective benzodiazepine receptor agonist, desmethylzopiclone is a selective partial agonist at the benzodiazepine site of α3-containing GABA receptor subtypes.^[1] It is also an antagonist to nicotinic acetylcholine receptors and NMDA receptors.^[1]

Desmethylzopiclone has been described as a potential anxio-selective metabolite of zolpiclone owing to its selective affinity for the modulation of α3-containing GABA receptor subtypes.^[1] Modulation of these GABA_A subtypes have been implicated as key mediators of the anxiolytic effects of benzodiazepines.^[2]

In forensic analysis

A method for the quantification of desmethylzopiclone from urine has been developed and may serve useful in forensic analysis of cases involving zolpiclone intoxication.^[3]

References

^ ^a ^b ^c Fleck MW (2002-08-01). "Molecular Actions of (S)-Desmethylzopiclone (SEP-174559), an Anxiolytic Metabolite of Zopiclone". The Journal of Pharmacology and Experimental Therapeutics. 302 (2): 612–618. doi:10.1124/jpet.102.033886. ISSN 0022-3565. PMID 12130723.
^ Rowlett JK, Platt DM, Lelas S, Atack JR, Dawson GR (2005-01-18). "Different GABA_A receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates". Proceedings of the National Academy of Sciences of the United States of America. 102 (3): 915–920. Bibcode:2005PNAS..102..915R. doi:10.1073/pnas.0405621102. ISSN 0027-8424. PMC 545524. PMID 15644443.
^ Nilsson GH, Kugelberg FC, Ahlner J, Kronstrand R (2014). "Quantitative Analysis of Zopiclone, N-desmethylzopiclone, Zopiclone N-oxide and 2-Amino-5-chloropyridine in Urine Using LC–MS-MS". Journal of Analytical Toxicology. 38 (6): 327–334. doi:10.1093/jat/bku042. PMID 24790062.

[Fleck_2002-1] Fleck MW (2002-08-01). "Molecular Actions of (S)-Desmethylzopiclone (SEP-174559), an Anxiolytic Metabolite of Zopiclone". The Journal of Pharmacology and Experimental Therapeutics. 302 (2): 612–618. doi:10.1124/jpet.102.033886. ISSN 0022-3565. PMID 12130723.

[2] Rowlett JK, Platt DM, Lelas S, Atack JR, Dawson GR (2005-01-18). "Different GABA_A receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates". Proceedings of the National Academy of Sciences of the United States of America. 102 (3): 915–920. Bibcode:2005PNAS..102..915R. doi:10.1073/pnas.0405621102. ISSN 0027-8424. PMC 545524. PMID 15644443.

[3] Nilsson GH, Kugelberg FC, Ahlner J, Kronstrand R (2014). "Quantitative Analysis of Zopiclone, N-desmethylzopiclone, Zopiclone N-oxide and 2-Amino-5-chloropyridine in Urine Using LC–MS-MS". Journal of Analytical Toxicology. 38 (6): 327–334. doi:10.1093/jat/bku042. PMID 24790062.

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