Synthesis and characterization of a BODIPY conjugate of the BCR-ABL kinase inhibitor Tasigna (nilotinib): evidence for transport of Tasigna and its fluorescent derivative by ABC drug transporters
We report the synthesis and characterization of a fluorescent derivative of Tasigna, a BCR-ABL kinase inhibitor recently approved by the Food and Drug Administration, to study its interaction with two major ABC transporters, P-glycoprotein (Pgp) and ABCG2, in in vitro and ex vivo assays. A fluorescent derivative of Tasigna, BODIPY FL Tasigna, inhibited the BCR-ABL […]
Role of L-type amino acid transporter 1 at the inner blood-retinal barrier in the blood-to-retina transport of gabapentin
In vivo blood-to-retina gabapentin transfer was evaluated by the rat carotid artery injection technique. In addition, gabapentin transport was examined using in vitro models of the inner (TR-iBRB2 cells) and outer BRB (RPE-J cells). The in vivo [(3)H]gabapentin transfer to the rat retina across the BRB was significantly reduced in the presence of unlabeled gabapentin, […]
P-gp Protein Expression and Transport Activity in Rodent Seizure Models and Human Epilepsy
We assess the viability of combining in vivo and ex vivo preparations of isolated brain capillaries from animal models of seizures and epilepsy as well as from patients with epilepsy to study P-gp at the blood-brain barrier. Exposing isolated rat brain capillaries to glutamate ex vivo upregulated P-gp expression to levels that were similar to […]