CJZ3, a lomerizine derivative, modulates P-glycoprotein function in rat brain microvessel endothelial cells

Aim: To investigate the modulatory effect of CJZ3, a lomerizine derivative, on P-glycoprotein (P-gp) function in rat brain microvessel endothelial cells (RBMEC). Methods: RBMEC were isolated and cultured in Dulbecco's modified Eagle's medium/F12 (1:1)medium, and the amount of intracellular rhodamine 123 (Rh123) was determined using a fluorescence spectrophotometer to evaluate the modulatory effect of CJZ3 on P-gp function. Results: The accumulation of Rh123 was potentiated in a concentration-dependent manner after incubation with CJZ3 for RBMEC, but not for human umbilical vein endothelial cells (HUVEC). CJZ3 caused the accumulation of intracellular Rh123 in a time-dependent manner and significantly decreased the efflux of Rh123 from the cells. The inhibitory effect of CJZ3 on P-gp function was reversible and remained for 120 min after CJZ3 (2.5 umol/L) was removed from the medium. Conclusion: CJZ3 has a potent in vitro effect on the inhibition of P-gp function.