Desmethylclomipramine
clomipramine metabolite
What it isThe N-desmethyl metabolite of clomipramine, markedly more noradrenergic than the parent.
Why it mattersIt shifts a clomipramine dose from serotonergic toward noradrenergic as it accumulates, which matters in OCD where serotonergic effect is what works.
What it changesCYP2D6 poor metabolizers accumulate the parent and less metabolite, so their profile is more serotonergic and more anticholinergic.
FDA-approved for
- OCD (metabolite of clomipramine)
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.
NRI-predominant metabolite; ~130x weaker at SERT than clomipramine.
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.