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Biotech / Medical : ACADIA Pharmaceuticals Inc (ACAD)
ACAD 22.37-1.5%Nov 3 9:30 AM EST
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To: tuck who wrote (481)6/18/2008 9:01:27 PM
From: rkrw  Read Replies (1) of 588
 
Looking into the failure a little more, I didn't realize this was one and the same as their clozapine metabolite program. They had never given a good reason for why it would lessen agranulocytosis. Still seems surprising it showed absolutely nothing. And surprising the market saw > 1/2 of acadia value in this.

ACP-104 as a Stand-Alone Treatment for Schizophrenia

Overview

ACP-104 is a small molecule drug candidate that we are developing as a stand-alone treatment for patients with schizophrenia. We believe that ACP-104 may provide an effective antipsychotic therapy with the added advantage of improving cognitive function in patients with schizophrenia. It is known that large amounts of ACP-104, or N-desmethylclozapine, are formed in the body after administration of clozapine. That is, clozapine is metabolized to ACP-104. We discovered that ACP-104 has a unique ability to stimulate m1 muscarinic receptors, which are widely known to play an important role in cognition. Since clozapine itself blocks the m1 muscarinic receptor, patients need to extensively metabolize clozapine into ACP-104 to stimulate this receptor and thereby overcome the blocking action of clozapine. Like clozapine, ACP-104 also interacts with 5-HT2A and dopamine receptors. Our research indicates that ACP-104 is a partial agonist that causes weak activation of dopamine D2 and D3 receptors, whereas clozapine and most other antipsychotic drugs block these dopamine receptors. These partial agonist properties of ACP-104 may lead to less motoric side effects than seen with most other antipsychotic drugs.

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