Lee H S, Go M L
Department of Pharmacology, National University of Singapore, Republic of Singapore.
Arch Int Pharmacodyn Ther. 1996 May-Jun;331(3):221-31.
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.
采用分光光度法研究了抗疟药甲氟喹对犬脑粗微粒体摄取和释放Ca2+的影响。甲氟喹抑制肌醇-1,4,5-三磷酸（IP3）诱导的Ca2+释放，IC50为42微摩尔，但对Ca2+摄取到囊泡中的抑制作用较弱（IC50：272微摩尔）。甲氟喹的这些作用与其对骨骼肌微粒体摄取和释放Ca2+的作用相反，在骨骼肌微粒体中，其主要作用是抑制Ca2+摄取到囊泡中。发现甲氟喹作为犬脑微粒体中IP3敏感储存库释放Ca2+的特异性抑制剂比奎宁更有效。应考虑该药物影响细胞IP3相关信号转导过程的可能性。
