norclozapine

Norclozapine, also known as N-desmethylclozapine (NDMC) and ACP-104, is the major active metabolite of clozapine, an atypical antipsychotic. Norclozapine was investigated as a small molecule drug candidate for schizophrenia but was discontinued after failing to demonstrate efficacy in clinical trials[1][2][3]. Mechanistically, norclozapine acts as a partial agonist at dopamine D2 and D3 receptors (unlike clozapine), a potent and efficacious agonist at muscarinic acetylcholine M1 receptor, a moderate-efficacy partial agonist at M2 receptor, weak partial agonist or antagonist at M3 receptor, silent antagonist at M4 receptor, and binds with high affinity to the M5 receptor[1][7]. It also acts on serotonin 5HT1C and 5HT2 receptors with higher affinity than clozapine[7]. Norclozapine may contribute to some of the cognitive effects associated with clozapine therapy due to its cholinergic activity but is not effective for treating positive symptoms of schizophrenia on its own[8].

Other names

norclozapineN-desmethylclozapineNDMCACP-104ACP104ACP 104