M1 receptor activation is a requirement for arecoline analgesia.

Arecoline, a drug obtained from the Areca Catechu L., induced a dose-dependent antinociception (0.3–1 mg kg−1 i.p.) which was prevented by the muscarinic antagonists pirenzepine (0.1 g per mouse i.c.v.) and S-(−)-ET-126 (0.01 g per mouse i.c.v.). A dose-dependent inhibition of the antinociception induced by arecoline was observed after inactivation of the M1 gene by an antisense oligodeoxyribonucleotide (aODN). This effect was detected 24 h after the last i.c.v. injection of aODN. These results indicate that arecoline antinociception is mediated by the activation of central M1 muscarinic receptors.