Effects of mefloquine on Ca2+ uptake and release by dog brain microsomes.
The effects of the antimalarial drug, mefloquine, on the uptake and release of Ca2+ by crude microsomes from dog brain were investigated using a spectrophotometric method. Mefloquine inhibited the inositol-1,4,5-phosphate (IP3)-induced Ca2+ release with an IC50 of 42 microM, but was a weaker inhibitor of the uptake of Ca2+ into the vesicles (IC50: 272 microM). These effects of mefloquine are in contrast to its actions on Ca2+ uptake and release by skeletal muscle microsomes, where its predominant effect was seen to be the inhibition of Ca2+ uptake into the vesicles. Mefloquine was found to be more potent than quinine as a specific inhibitor of Ca2+ release from IP3-sensitive stores in dog brain microsomes. The possibility of the drug affecting cellular IP3-linked signal transduction processes should be considered.
Lee
H S
HS
Department of Pharmacology, National University of Singapore, Republic of Singapore.
Go
M L
ML
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D015544:Inositol 1,4,5-Trisphosphate / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D015767:Mefloquine / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects; D011803:Quinine / Q000494:pharmacology
D000962:Antimalarials; D015544:Inositol 1,4,5-Trisphosphate; D011803:Quinine; D002118:Calcium; D015767:Mefloquine