Correlation between Pharmacoresistance in Epilepsy, Seizure-Induced P-glycoprotein Overexpression, and the Potential Role of Cyclooxygenase-2 Overexpression | ||||
| Suez Canal University Medical Journal | ||||
| Article 6, Volume 27, Issue 4, April 2024, Page 0-0 | ||||
| Document Type: Review Article | ||||
| DOI: 10.21608/scumj.2024.430733 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Reham M. Elsayed   ; Amira S. Mohamed; Mona K. Tawfik; Magda M. Hagras
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| Clinical Pharmacology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt | ||||
| Abstract | ||||
| Background: Epilepsy is a chronic neurological disease. However, about third of epileptic patients are refractory to treatment. Antiseizure drugs (ASDs) must traverse the blood brain barrier (BBB) in an adequate therapeutic concentration, which is capable to activate specific receptors sites. The over expression of drug transporters at the BBB could be considered as one of the most important causes of the development of refractoriness in epilepsy. P-glycoprotein (P-gp) overexpression at the BBB during seizures had been linked to decreased brain uptake of ASDs and thus could play an important role in pharmacoresistant epilepsy. Cyclooxygenase-2 (COX-2) plays a crucial role in hyperexcitability, post seizure inflammation, and it is thought to contribute in the secondary damage that develops in brain after seizures. Also, elevated COX-2 activity may participate in P-gp upregulation during seizures. Consequently, COX-2 inhibition can provide neuroprotective effect, decreased P-gp expression, and enhanced uptake of ASDs at the BBB. Objective: To investigate the potential effect of COX-2 inhibition in suppressing P-gp expression to overcome the pharmacoresistance that develops after chronic use of ASDS. Methods: The data used in the present study were collected by searching the keyword combinations of medical subject heading (mesh) of “pharmacoresistance”, “antiseizure drugs”, “P-glycoprotein”, “COX-2 inhibition”, using scientific search engines and databases in Google Scholar, Science Direct, PubMed, Cochrane Database of Systematic Reviews, and Scopus. Results: P-gp suppression using inhibitors like COX-2 inhibitors, had improved the pharmacoresistance that developed with chronic use of ASDS. Conclusion: COX-2 inhibition was accompanied with downregulation of P-gp expression at the BBB, with a consequent decreased inflammation, increased ASDS level, and decreased pharmacoresistance. | ||||
| Keywords | ||||
| P-glycoprotein; Antiseizure drugs; Pharmacoresistance; ABCB1 gene; Cyclooxygenase-2 | ||||
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