Desmethylzopiclone Explained

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.

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. Modulation of these GABA_A subtypes have been implicated as key mediators of the anxiolytic effects of benzodiazepines.^[2]

In forensic analysis

The quantification of desmethylzopiclone from urine has been demonstrated and may serve useful in forensic analysis of cases involving zolpiclone intoxication.^[3]

Notes and References

1. Fleck . Mark W. . 2002-08-01 . Molecular Actions of (S)-Desmethylzopiclone (SEP-174559), an Anxiolytic Metabolite of Zopiclone . Journal of Pharmacology and Experimental Therapeutics . en . 302 . 2 . 612–618 . 10.1124/jpet.102.033886 . 0022-3565 . 12130723.
2. Rowlett . James K. . Platt . Donna M. . Lelas . Snjezana . Atack . John R. . Dawson . Gerard R. . 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 . en . 102 . 3 . 915–920 . 10.1073/pnas.0405621102 . free . 0027-8424 . 545524 . 15644443. 2005PNAS..102..915R .
3. Quantitative Analysis of Zopiclone, N-desmethylzopiclone, Zopiclone N-oxide and 2-Amino-5-chloropyridine in Urine Using LC–MS-MS . Journal of Analytical Toxicology . 2014 . 10.1093/jat/bku042 . Nilsson . Gunnel H. . Kugelberg . Fredrik C. . Ahlner . Johan . Kronstrand . Robert . 38 . 6 . 327–334 . 24790062 .