Desmethylclozapine

Desmethylclozapine

Systematic (IUPAC) name
8-chloro-11-piperazin-1-yl-5H-dibenzo[b,e][1,4]diazepine
Clinical data
Legal status	Uncontrolled
Routes	Oral
Identifiers
CAS number	6104-71-8
ATC code	None
PubChem	CID 2820
ChemSpider	14126465
UNII	1I9001LWY8
ChEMBL	CHEMBL845
Chemical data
Formula	C17H17ClN4
Mol. mass	312.80 g/mol
SMILES Clc1ccc2Nc4ccccc4C(=N\c2c1)/N3CCNCC3

N-Desmethylclozapine (NDMC), or norclozapine, is a major active metabolite of the atypical antipsychotic drug clozapine.^[1][2] Unlike clozapine, it possesses intrinsic activity at the D₂/D₃ receptors, and acts as a weak partial agonist at these sites similarly to aripiprazole and bifeprunox.^[3] Notably, NDMC has also been shown to act as a potent and efficacious agonist at the M₁ and δ-opioid receptors, unlike clozapine as well. Therefore, NDMC is considered a delta-opioid agonist.^[4][5][6] It was hypothesized that on account of these unique actions, NDMC might underlie the clinical superiority of clozapine over other antipsychotics. However, clinical trials found NMDC itself ineffective in the treatment of schizophrenia.^[7][8] This may be because it possesses relatively low D₂/D₃ occupancy compared to 5-HT₂ (<15% versus 64-79% at a dose of 10–60 mg/kg s.c. in animal studies).^[9] In any case, though not useful in the treatment of positive symptoms on its own, it cannot be ruled out that NDMC may contribute to the improvement of cognitive and/or negative symptoms with clozapine.^[7]

See also

• Clozapine

References