Nordoxepin

Overview

Nordoxepin, also known as N-desmethyldoxepin, is an organic compound. A colorless solid, it attracted attention as the major active metabolite of the tricyclic antidepressant (TCA) doxepin (Sinequan). It has been found to play a significant role in the antidepressant effects of doxepin.[1][2] WP

Nordoxepin is a mixture of (E) and (Z) stereoisomers. Whereas pharmaceutical doxepin is supplied in an approximate 17:3 ratio mixture of (E)- and (Z)-stereoisomers and plasma concentrations of doxepin remain roughly the same as this ratio with treatment, plasma levels of the (E)- and (Z)-stereoisomers of nordoxepin, due to stereoselective metabolism of doxepin by cytochrome P450 enzymes, are approximately 1:1.[1] WP

Nordoxepin is pharmacologically active similarly to doxepin. In general, the demethylated variants of tertiary amine TCAs like doxepin are much more potent norepinephrine reuptake inhibitors, less potent serotonin reuptake inhibitors, and less potent in their antiadrenergic, antihistamine, and anticholinergic activities.[3–6] WP

Nordoxepin is formed from doxepin mainly by CYP2C19 (>50% contribution), while CYP1A2 and CYP2C9 are involved to a lesser extent, and CYP2D6 and CYP3A4 are not involved. Hydroxylation of doxepin and nordoxepin is mediated mainly by CYP2D6. Total exposures to both doxepin and nordoxepin differ by almost 10-fold in CYP2D6 ultra-rapid versus poor metabolizers. Both doxepin and nordoxepin are also transformed into glucuronide conjugates. The elimination half-life of nordoxepin is approximately 31 hours, which is almost twice that of doxepin (mean 17 hours).[2][7][8] WP

Chemistry

Formula

C18H19NO PC

CAS number

1225-56-5 PC

Molar mass (g/mol)

265.3 PC

IUPAC name (computed by PubChem)

3-(6H-benzo[c][1]benzoxepin-11-ylidene)-N-methylpropan-1-amine PC

SMILES

CNCCC=C1C2=CC=CC=C2COC3=CC=CC=C31 PC

InChIKey

HVKCEFHNSNZIHO-UHFFFAOYSA-N PC

PubChem CID

4535

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Williams DA. Foye's Principles of Medicinal Chemistry. 24 January 2012
2. Journal / agency Kirchheiner J, Henckel HB, Franke L, Meineke I, Tzvetkov M, Uebelhack R, Roots I, Brockmöller J. Impact of the CYP2D6 ultra-rapid metabolizer genotype on doxepin pharmacokinetics and serotonin in platelets. Pharmacogenetics and Genomics. August 2005. doi:10.1097/01.fpc.0000167331.30905.9e · PMID 16007002
3. Journal / agency Weber J, Siddiqui MA, Wagstaff AJ, McCormack PL. Low-dose doxepin: in the treatment of insomnia. CNS Drugs. August 2010. doi:10.2165/11200810-000000000-00000 · PMID 20658801
4. Other Dawkins K, Manji HK, Potter WZ. Pharmacodynamics and Drug Development: Perspectives in Clinical Pharmacology. 20 September 1994
5. Other Baumann P, Hiemke C. Metabolism of Drugs and Other Xenobiotics. 23 February 2012
6. Other Nelson JG. The American Psychiatric Publishing Textbook of Psychopharmacology. 2009
7. Journal / agency Härtter S, Tybring G, Friedberg T, Weigmann H, Hiemke C. The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19. Pharmaceutical Research. July 2002. doi:10.1023/a:1016478708902 · PMID 12180536
8. Other Sinepin Capsules 25mg - Summary of Product Characteristics (SPC). 22 September 2011

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.