MEMANTINE, AS A P-GLYCOPROTEIN EXPRESSION MODULATOR, ENHANCES LEVETIRACETAM THERAPEUTIC RESPONSE IN EPILEPTIC PATIENTS

  • SAHAR AHMED HARBY Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
  • RASHA A NASSRA Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
  • JAIDAA F MEKKY Department of Neuropsychiatry, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
  • SAMIA M ALI Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
  • CHERINE A ISMAIL assisstant professor, clinical pharmacology department, faculty of medicine, alexandria university

Abstract

Objective: The principal aim of the present study was to assess the importance of multidrug transporter; P-glycoprotein (P-gp) as a potential therapeutic target in patients with epilepsy. Can P-gp transporter expression modulation by memantine add to the standard antiepileptic drugs (AEDs) response?


Methods: A cohort of 56 epilepsy patients was included in a 4 monthly visits prospective study. Patients were on levetiracetam (LEV) 1000 mg/ day alone or combined with other AEDs. They were randomly assigned into two groups; LEV only group including LEV-treated patients and LEV + memantine group including patients on LEV with add-on oral memantine 10 mg/day until the end of the study. During monthly follow-up visits, therapeutic responses were evaluated for each patient by recording the monthly seizures frequency. Blood samples were drawn from every patient twice (on the first and last visits) for assessment of P-gp mRNA expression level.


Results: Fifty patients completed the study. At the end of 4th month, LEV only group showed a non-significant decrease in P-gp expression and seizure frequency compared to the 1st month, whereas, in LEV + memantine group, P-gp expression was significantly reduced and associated with significant seizure control.


Conclusion: Memantine by hindering P-gp overexpression was apt to enhance LEV efficacy and exhibit a better seizure control.

Keywords: P-glycoprotein, N-methyl d-aspartate receptor, Memantine, Levetiracetam, Epilepsy

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HARBY, S. A., R. A. NASSRA, J. F MEKKY, S. M ALI, and C. A ISMAIL. “MEMANTINE, AS A P-GLYCOPROTEIN EXPRESSION MODULATOR, ENHANCES LEVETIRACETAM THERAPEUTIC RESPONSE IN EPILEPTIC PATIENTS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 5, Mar. 2020, pp. 104-8, doi:10.22159/ajpcr.2020.v13i5.37011.
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