N-desmethylclozapine

N-desmethylclozapine (NDMC), also known as ACP-104, is a small molecule and the primary active metabolite of the atypical antipsychotic clozapine. It is distinguished from its parent compound by its unique pharmacological profile, specifically acting as a partial agonist at the **muscarinic M1 receptor**, whereas clozapine acts as an antagonist. NDMC also functions as an agonist at the **5-HT1A receptor** and an antagonist at **5-HT2A**, **5-HT2C**, and **dopamine D2/D3 receptors**. The stimulation of M1 receptors by NDMC is hypothesized to enhance cognitive function by increasing the release of acetylcholine and dopamine in the prefrontal cortex, potentially addressing the cognitive deficits associated with schizophrenia. ACADIA Pharmaceuticals developed NDMC (as ACP-104) for the treatment of schizophrenia and related cognitive impairments, but clinical development was terminated following a Phase II trial that failed to meet its primary efficacy endpoints.

Other names

norclozapine