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Minocycline: A Reasonable Choice for Combination Therapy in Management of Pharmacoresistant Epilepsy

Hamed Ghavimi, Esmael Izadpanah, Kambiz Hassanzadeh

Abstract


About 30% of epileptic patients do not respond to the usual antiepileptic drugs (AEDs). There is accumulating evidence demonstrating that multi-drug transporters such as P-glycoprotein (P-gp) are over-expressed in capillary endothelial cells and astrocytes in epileptogenic brain tissue, resulting in impaired AEDs access to the site of action. Also it has been indicated that glutamate release is critically involved in the over-expression of P-gp at the blood brain barrier (BBB). Glutamate signaling via the N-methyl-D-aspartate (NMDA) receptor is coupled to elevation of Ca+2, generation of intracellular reactive oxygen species (ROS) and activation of cyclooxygenases-2 (COX-2), increase protein expression and transport activity of P-gp in isolated rat brain microvessels endothelial cells (BMECs) capillaries. In addition conditions that generate ROS have been shown to increase P-gp expression in cells derived from liver and kidney. Minocycline, a second-generation tetracycline, has been reported to exert neuroprotective effects over various experimental and clinical models. It has been indicated that minocycline inhibits p-glycoprotein (g-gp). The involvement of antioxidant system, prevention of the activation of Ca+2 dependent intracellular pathways, as well as a marked decrease in glutamate release, blockade of inflammation pathway inhibiting molecules such as COX-2 and inflammatory mediator such as reactive oxygen species (ROS) and Prostaglandin E2 (PGE2) have been reported as neuroprotective effects of Minocycline. Therefore it is hypothesized that minocycline is a reasonable choice for combination therapy in management of pharmacoresistant epilepsy.

Key words: Minocycline; Pharmacoresistant Epilepsy; P-glycoprotein; Antiepileptic Drug

 


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