Abstract: AIM:To study the effect of Lomerizine on the activity of P-glycorprotein (P-gp)in primary cul- tured rat brain microvessel endothelial cells (RBMECs). METHODS:Flow cytometry was used to study the efflux of rhodamine123 (Rh123)and expression of P-gp in RB- MECs.RT-PCR was used to measure the expression in mRNA level of mdr1 gene in RBMECs .Transwell model was used to detect the influence of Lomerizine on the transport of Rh123 through RBMECs monolayer.RE- SULTS :Lomerizine inhibited the efflux of Rh123 in RB- MECs.No changes of P-gp and mdr1 gene mRNA ex- pression were detected in RBMECs after the treatment with 30 μ mol·L ^-1 Lomerizine for 72 h .In the study of Transwell model , Lomerizine increased significantly the transport of Rh123 through RBMECs monolayer from up- per compartments to lower compartments, and inhibited obviously the transport in reverse direction .CONCLU- TION:The effect of Lomerizine on the activity of P-gp was mainly via its direct inhibitory effect on the function of P-gp in RBMECs and the transport of P-gp substrates in BBB may be affected by lomerizine.

Key words: P-glycoprotein ;Lomerizine ;rat brain microvessel endothelialcells ;flow cytometry ;transwell , rhodamine123