The effect of 5-HT3 receptor antagonists on the writhing response in mice.

1. The ability of several 5-HT3 receptor antagonists (MDL 72,222EF, the methyl quaternary ammonium salt of MDL 72,222, dolasetron, tropisetron, granisetron and ondansetron) to inhibit writhing induced in the mouse by either 5-hydroxytryptamine (5-HT), acetylcholine or acetic acid was examined. 2. All of the 5-HT3 receptor antagonists were able to inhibit writhing induced by acetylcholine. MDL 72,222EF and tropisetron were also able to inhibit writhing induced by 5-HT and acetic acid but higher doses were required to have the same effect as against acetylcholine. Dolasetron inhibited writhes induced by 5-HT but failed to significantly affect writhes induced by acetic acid. 3. MDL 72,222EF and its quaternary salt were more potent and had a more rapid onset of action after i.p. than after s.c. administration. 4. 2-Methyl-5-HT did not induce writhing at doses up to 4 mg/kg i.p., whereas 5-HT dose-dependently induced writhing over the range 0.5-2 mg/kg. 5. These results show that 5-HT3 receptor antagonists can inhibit writhes induced by a variety of compounds and this appears to be a local action. However, the inability of 2-methyl-5-HT to induce writhing and the high doses of antagonist required indicate that further studies are required to establish a role for 5-HT3 receptors in this effect.