August 04, 2004

New Research to Improve Schizophrenia Cognition

Acadia Pharmaceutical recently published a research study showing that the compound ACP-104 (N-desmethylclozapine) is similar in its chemical action to the drug clozapine (trade name Clorazil), the only anti-psychotic that partially improves cognition in schizophrenia patients.

ACP-104 (the principal metabolite of clozapine) acts on m1 muscarinic receptors in the brain that affect cognitive abilities. Based on the mechanism of action of the metabolite, researchers hypothesize that it might be responsible for the cognitive benefits of clozapine. The research notes that only ACP-104, not clozapine itself, is responsible for stimulating the muscarinic receptors. They are looking at possibly developing the metabolite compound into a new therapy for schizophrenia.

"By directly administering ACP-104, thereby avoiding the highly variable step of having it metabolized in the body from clozapine, we hope to offer an improved therapy that provides a more consistent cognitive benefit to patients," says Dr. Mark Brann, President and Chief Scientific Officer of Acadia Pharmaceuticals.

The research also included drug blood level analysis of 92 schizophrenia patients taking clozapine. Results noted that patients with higher levels of ACP-104 metabolite (relative to clozapine) in their blood performed better on cognitive performance tests.

For more information, see the following press release: 'Acadia Study Links ACP-104 to Improved Cognition in Schizophrenia Patients' (Aug 3, 2004) from PR Newswire (

To read the published research abstract, see 'The Role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine' (Psychopharmacology, 2004 Jul 16) at Pubmed (

For more information about the drug clozapine, see the Medications section on the website (


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