Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : ACADIA Pharmaceuticals Inc (ACAD) -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (332)	7/17/2007 11:34:35 AM
From: tuck	Respond to of 588

>>>> Eur J Pharmacol. 2007 Jun 29; [Epub ahead of print] AC260584 (4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one), a selective muscarinic M(1) receptor agonist, increases acetylcholine and dopamine release in rat medial prefrontal cortex and hippocampus. Li Z, Bonhaus DW, Huang M, Prus AJ, Dai J, Meltzer HY. Psychiatry Department, Vanderbilt University School of Medicine, Nashville, TN USA. Both muscarinic and nicotinic receptors are implicated in cognition. We have previously suggested that stimulation of the muscarinic M(1) receptor has a beneficial effect on cognition, based upon evidence that the muscarinic M(1) receptor agonist of N-desmethylclozapine, the major metabolite of clozapine, may contribute to the ability of clozapine to improve some domains of cognition in schizophrenia. Present study examined the effectiveness of a new muscarinic M(1) receptor agonist, 4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one (AC260584), to increase the release of acetylcholine and dopamine in the rat medial prefrontal cortex and hippocampus. Using microdialysis in awake, freely moving rats, AC260584, 3 and 10, but not 1 mg/kg (s.c.), significantly increased dopamine release in the medial prefrontal cortex and hippocampus. However, only the high dose of AC260584, 10 mg/kg (s.c.), significantly increased acetylcholine release in these regions. Moreover, the increases in acetylcholine release produced by AC260584, 10 mg/kg, were attenuated by the muscarinic M(1) receptor antagonist telenzepine (3 mg/kg, s.c.) but not by the 5-HT(1A) receptor antagonist N-[2-(4-2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridyl) cyclohexanecarboxamide (WAY100635, 0.2 mg/kg, s.c.). However, the increase in dopamine release produced by 10 mg/kg AC260584 was blocked by both telenzepine and WAY100635. In addition, pretreatment with the atypical antipsychotic drug risperidone (0.1 mg/kg, s.c.) potentiated AC260584 (1.0 mg/kg, s.c.)-induced acetylcholine and dopamine release in the medial prefrontal cortex. These findings suggest that the muscarinic M(1) receptor agonist property of AC260584 contributes to its enhancement of cortical acetylcholine and dopamine efflux. Therefore, AC260584, as well as other muscarinic M(1) receptor agonists, may be a valuable target for the development of drugs which can improve the cognitive deficits in schizophrenia and perhaps other neuropsychiatric disorders, as well.<< Annoyingly, ACAD still does not have a pipeline chart, nor a publications index, nor do they nor talk much about the early stuff. Is AC260584 being developed, or what? Cheers, Tuck<<