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Norclozapine

clozapine metabolite

What it isN-desmethylclozapine, the major active metabolite of clozapine, with muscarinic M1 agonism the parent lacks.

Why it mattersIts M1 agonism is the leading explanation for clozapine’s cognitive and procognitive effects, and its ratio to clozapine tracks adherence and metabolism.

What it changesA norclozapine-to-clozapine ratio above about 0.8 suggests poor adherence with a recent dose; a very low ratio suggests CYP1A2 inhibition.

FDA-approved for

NO BOXED WARNINGS

Principal riskLittle in its own right; see the parent drug

Classes and tags

Clinical profile

Direct muscarinic antagonism0 / 4

Mechanism of action: Norclozapine ballicule

Norclozapine ballicule: receptor binding, kinetics and half-life diagram

Open Norclozapine in the interactive console ↗

Memory aids: mascots and interaction avatars

Norclozapine mascot mnemonic cartoon
“Nor Clozapine”
Symbol in mouth is nor → nitrogen has lost an alkyl substituent
Light blue → cholinergic / muscarinic
Thinking cap → cognitive benefits (M1 agonist)
Hypersalivation (likely multifactorial, M1 contributing)

Open Norclozapine in the interactive console ↗