Antipsychotic-like behavioral effects and cognitive enhancement by a potent and selective muscarinic M-1 receptor agonist, AC-260584

AC-260584 (4-[3-(4-butylpiperidin-1-yl)-propyll-7-fluoro-4H-benzo[1,4]oxazin-3-one) is a potent and selective muscarinic M, receptor agonist. AC-260584 was evaluated in animal models: antipsychotic-like effects were tested by the ability to reduce amphetamine- and MK-801-induced hyperactivity and apomorphine-induced climbing; catalepsy was assessed by measuring step-down latency; spatial memory was tested by using the Morris water maze. AC-260584 reduced amphetamine- and MK-801-induced hyperactivity and apomorphine-induced climbing. In contrast to haloperidol, AC-260584 did not produce catalepsy. AC-260584 enhanced performance in the water maze during a probe test without a platform after 6 days of training, similar to the positive control tacrine. These data indicate that AC-260584 has a behavioral profile consistent with antipsychotic-like efficacy with the potential to improve cognitive performance and shows reduced liability for extrapyramidal symptoms.