CENTRAL MUSCARINIC ANTINOCICEPTION INDUCED BY ET-142 AND SS-20 IN RODENTS

The antinociceptive effects of ET-142 (10-50 mg kg(-1) sc; 10-30 mu g per mouse icy) and SS-20 (10-50 mg kg(-1) sc; 5-30 mu g per mouse icy) were examined in mice by using the hot-plate and abdominal constricti on tests. A similar antinociceptive profile for both compounds (20-40 mg kg(-1) ip) was also observed in rats using the paw pressure test. I n the antinociceptive dose-range, ET-142 and SS-20 did not impair mous e gross behavior and motor coordination evaluated, respectively, by th e Irwin and rotarod tests. The increase in-the pain threshold produced by ET-142 and SS-20 was prevented by atropine, dicyclomine, pirenzepi ne, and hemicholinium-a, but not by naloxone, atropine methyl bromide, and CGP 35348. In vitro experiments showed that the two investigated compounds amplified electrically evoked guinea pig ileum contractions. On the basis oi the above data, it can be postulated that ET-142 and SS-20 exert their antinociceptive effect through a potentiation of cen tral cholinergic transmission. (C) 1997 Wiley-Liss, Inc.