EFFECTS OF MEFLOQUINE ON CA2-MUSCLE( UPTAKE BY CRUDE MICROSOMES OF RABBIT SKELETAL)

The effects of the antimalarial agent, mefloquine, and its derivatives on Ca2+ uptake and release by crude microsomes from the rabbit skelet al muscle were investigated using a spectrophotometric method. These c ompounds diminished the rate of Ca2+ uptake and inhibited the Ca2+ pum p ATPase activity of the microsomes. Except for quinine, they appear t o have negligible effects on Ca2+ release channels, Of the compounds i nvestigated, mefloquine had the most pronounced effect on Ca2+ uptake and was also the most potent (noncompetitive) inhibitor of Ca2+-ATPase (K-i: 53 mu M). The ability of mefloquine to interfere with Ca2+ sequ estration into the sarcoplasmic reticulum via inhibition of the Ca2+ p ump ATPase, may explain some of its actions on the isolated skeletal m uscle (relaxation, inhibition of twitch responses, diminution of caffe ine contractures) observed in earlier studies. However, its contractil e effects are less readily explained, The novel finding that mefloquin e inhibits the Ca2+ pump ATPase of the skeletal muscle, suggests that it may have similar effects on the Ca2+-ATPases of other tissues.