Action of mefloquine on agonist-induced contractions of the guinea-pig isolated ileum

Abstract

Responses of the guinea-pig isolated ileum to cumulative concentrations of acetylcholine (ACh), histamine (H), and prostaglandin E2 (PGE2) were obtained in the presence or absence of mefloquine or quinine. The effects of increasing the external calcium concentration and the presence of a low concentration (1.8 nmol/l) of PGE2 on the mefloquine- and quinine-induced inhibition of the ACh cumulative dose-response curves were also investigated. Mefloquine (1-10 μmol/l) and quinine (50-100 μmol/l) both caused a dose-dependent non-parallel right shift of the log concentration-response curve of every agonist. Mefloquine is a more potent inhibitor of PGE2-induced responses whereas quinine inhibited all three agonist-induced responses to the same extent. Increasing the external calcium concentration enhanced the inhibitory effects of both drugs on ACh-induced responses. Pre-incubation with 1.8 mmol/l PGE2 had a similar effect. The actions of mefloquine on ACh- and H-induced contractions are non-specific, like other antimalarials, but its greater inhibitory action on PGE2 may involve a more complex effect.