Nordoxepin
doxepin metabolite
What it isThe N-desmethyl metabolite of doxepin, more noradrenergic and less antihistaminic than the parent.
Why it mattersIt shifts the balance of a doxepin dose from sedation toward noradrenergic effect as it accumulates.
What it changesIt is why doxepin becomes less sedating over weeks, and why the low-dose hypnotic indication uses doses too small to generate much of it.
FDA-approved for
- depression (metabolite of doxepin)
NO BOXED WARNINGS
Principal riskLittle in its own right; see the parent drug
Classes and tags
Clinical profile
Serotonicity
This drug is routinely called serotonergic. By Gillman’s human-effect criteria it does not raise serotonin in the synapse.
It binds the serotonin transporter, and its SERT peg is drawn to that textbook affinity. The pale halo around the peg marks binding that, by Gillman’s human-effect criteria, does not produce clinical serotonin reuptake inhibition.
Gillman’s four human testsA measurable SERT affinity that fails all four is not clinical serotonicity.
- Retarded orgasm
- Efficacy in OCD and cataplexy
- Clonus and hyperreflexia in single-drug overdose
- Serotonin toxicity when combined with an MAOI
Evidence confidenceModerate
Background: what serotonicity is · what is and is not an SRI · what counts as a relevant MAOI.