Jul 14, 2007

AC260584 (4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one), a selective muscarinic M1 receptor agonist, increases acetylcholine and dopamine release in rat medial prefrontal cortex and hippocampus

European Journal of Pharmacology
Zhu LiHerbert Y Meltzer

Abstract

Both muscarinic and nicotinic receptors are implicated in cognition. We have previously suggested that stimulation of the muscarinic M1 receptor has a beneficial effect on cognition, based upon evidence that the muscarinic M1 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 M1 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 M1 receptor antagonist telenzepine (3 mg/kg, s.c.) but not by the 5-HT1A receptor antagonist N-[2-(4-2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridyl) cyclo...Continue Reading

  • References36
  • Citations14

Mentioned in this Paper

Dialysis Solutions
Antipsychotic Effect
Atypical Antipsychotic [EPC]
Acetylcholinesterase Inhibitors
Amphetamine
Cortex Bone Disorders
Adrenal Cortex Diseases
Prefrontal Cortex
Neostriatum
Extracellular

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