Hydroxynefazodone
nefazodone metabolite
What it isThe hydroxy metabolite of nefazodone, retaining the parent’s 5-HT2 antagonism.
Why it mattersIt contributes to nefazodone’s therapeutic effect while sharing its CYP3A4 inhibition.
What it changesIt does not explain the hepatotoxicity, which is attributed to a separate quinone-imine pathway.
FDA-approved for
- depression (metabolite of nefazodone)
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.