Antinociceptive property of the nicotinic agonist AG4 in rodents

AG-4 has been characterized as a nicotinic agonist by binding (Ki = 26 ± 1.4 mM) and in vitro functional assays. The antinociceptive effect of AG-4 was examined in mice and rats, using the hot plate, abdominal constriction, and paw-pressure tests. In both species, AG-4 (25–150 mg per mouse icv; 100–150 mg per rat icv) produced significant antinociception which was prevented by mecamylamine (2 mg kg–1 ip) and pempidine (3 mg kg–1 i.p.), but not by atropine (5 mg kg–1 ip), naloxone (1 mg kg–1 ip) and CGP 35348 (100 mg kg–1 ip). In the antinociceptive dose range, AG-4 did not impair mice motor coordination and spontaneous motility as well as inspection activity. The present results have shown that AG-4 is a compound endowed with antinociceptive properties mediated via nicotinic activation and may be a promising beginning for new nicotinic agonists.