Desmethylsertraline
sertraline metabolite
What it isThe N-desmethyl metabolite of sertraline, far weaker at SERT but with a much longer half-life.
Why it mattersIts weak activity is why sertraline has little accumulation effect despite a metabolite that persists three times longer.
What it changesIt contributes little clinically, which is part of why sertraline is predictable across patients.
FDA-approved for
- depression (metabolite of sertraline)
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.
~260x weaker at SERT than sertraline; no independent clinical SRI role.
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.