Antipsychotic-like behavioral effects and cognitive enhancement by a potent and selective muscarinic M-sub-1 receptor agonist, AC-260584.
AC-260584 (4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one) is a potent and selective muscarinic M-sub-1 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.
Vanover
Kimberly E
KE
ACADIA Pharmaceuticals Inc., San Diego, CA, USA. kvanover@intracellulartherapies.com
Veinbergs
Isaac
I
Davis
Robert E
RE
D000661:Amphetamine; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D048588:Benzoxazines / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D016291:Dizocilpine Maleate; D004347:Drug Interactions; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018697:Nootropic Agents / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects; D013619:Tacrine / Q000494:pharmacology
D014150:Antipsychotic Agents; D048588:Benzoxazines; D018697:Nootropic Agents; D013619:Tacrine; D016291:Dizocilpine Maleate; D000661:Amphetamine; C516553:4-(3-(4-butylpiperidin-1-yl)propyl)-7-fluoro-4H-benzo(1,4)oxazin-3-one