Effects of mefloquine on the isolated chick biventer cervicis and rat phrenic nerve hemidiaphragm preparations

Abstract

The effects of the antimalarial agent mefloquine on skeletal muscle and its neurotransmission were investigated on the isolated chick biventer cervicis and rat phrenic nerve hemidiaphragm. At concentrations of 64, 128 and 257 microM, mefloquine reduced twitch contraction responses to nerve stimulation, and inhibited carbachol- and KCl-induced contractures of avian muscle. Qualitatively similar responses were observed for chloroquine (257 microM) and quinine (512 microM) but the inhibitory effects of mefloquine were more pronounced and less readily reversible. On the rat phrenic nerve hemidiaphragm, mefloquine (50, 75 and 100 microM) inhibited twitch contractions stimulated indirectly via the nerve. When nerve transmission has been blocked with alpha-bungarotoxin, mefloquine inhibited twitch responses obtained by direct stimulation of the hemidiaphragm. The present findings indicate that its prime action seems to be on muscle contractility, possibly by inhibiting excitation-contraction coupling.