Schizophrenia Daily News Blog

ACP-104 Future Schizophrenia Drug?

ACADIA Pharmaceuticals is announcing the molecular properties of ACP-104 that would make it an effective antipsychotic. They are currently developing this drug so it can be used to treat schizophrenia in the future.

The following information looks like it comes (either directly, or indirectly) from ACADIA Pharmaceuticals marketing department - so, as with any marketing material from any company, we think you should be skeptical of the information. It looks interesting, but all company marketing departments tend to highlight the positive points of their products, while avoiding mention of any possible negative aspects, and pharmaceutical companies are no different in this respect. The most reliable information is generally from independent sources (with no monetary ties to the medication), such as NIMH (National Institute of Mental Health) – sponsored studies.

ACADIA Pharmaceuticals Inc. , a biopharmaceutical company utilizing innovative technology to fuel drug discovery and clinical development of novel treatments for central nervous system disorders, today announced publication of research in the Journal of Pharmacology and Experimental Therapeutics (JPET) that shows that ACP-104, the major metabolite of clozapine, is a partial agonist that causes weak activation of dopamine D2 and D3 receptors, whereas clozapine and most other antipsychotic drugs block these receptors. ACADIA believes that these partial agonist properties of ACP-104 may lead to less motoric side effects than seen with most other antipsychotic drugs. ACADIA is developing ACP-104 as a novel therapy for schizophrenia, with the added potential benefit of improving cognition.

The JPET article (August 31, 2005, e-pub) describes the research conducted by ACADIA scientists of 41 marketed and experimental antipsychotic drugs and their ability to alter the activities of dopamine D2, D3, and D4 receptors. Using ACADIA's proprietary R-SAT(R) technology platform, the scientists developed assays that detect subtle changes in the activities of these receptors. Among the 41 drugs, only two of them, ACP-104 and aripiprazole (marketed as ABILIFY(R)), were partial agonists causing weak activation of dopamine D2 and D3 receptors. Most antipsychotic drugs were shown to block these dopamine receptors. Prior research has shown that blockade of the dopamine receptors may cause undesirable motoric side effects, including Parkinson-like symptoms and tardive dyskinesia.

"Precisely balancing dopaminergic tone with an antipsychotic drug being a partial dopamine agonist is a very exciting concept that I have championed for many years," said Arvid Carlsson, M.D., Ph.D., Professor Emeritus of Pharmacology at the University of Goteborg, Sweden, and winner of the 2000 Nobel Prize for Medicine. "I find it most intriguing that ACP-104, the major metabolite of the first atypical antipsychotic drug, clozapine, has this property."

About ACP-104
ACP-104 is a small molecule drug candidate that ACADIA has discovered and is developing as a novel, stand-alone therapy for schizophrenia. It combines an atypical antipsychotic efficacy profile with the added potential benefit of improving cognition, one of the major challenges in treating schizophrenia today. ACP-104, or N-desmethylclozapine, is the major metabolite of clozapine, and has a unique ability to stimulate M1 muscarinic receptors. The M1 muscarinic receptors are widely known to play an important role in cognition. ACADIA is currently conducting initial Phase II studies to evaluate safety, tolerability, and preliminary efficacy of ACP-104 in patients with schizophrenia.

ACP-104 has not been FDA approved in the US and there are few clinical trials that have studied its effects. Just remember to be skeptical of trials done by those who are marketing the medication (in this case, ACP-104).

SOURCE: ACADIA Pharmaceuticals You can view the full press release by clicking here.

To view another article on ACP-104 and its effects, click here.