en Cellular and molecular Neuroscience Cellular and molecular Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue.<br> <strong>Methods</strong>: We have studied P-gp and MRP-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15).<br> <strong>Results</strong>: Statistically significant over expression of both P-gp (P<0.0001) and MRP-1 (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of P-gp was more pronounced than MRP-1. Immunohistochemistry of the patient group showed increased immunoreactivity of P-gp at blood-brain barrier and increased reactivity of MRP-1 in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy.<br> <strong>Conclusion</strong>: Our results suggested that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy. P-gp and MRP-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.</div> Drug-efflux transporters, Drug-resistant epilepsy, Mesial temporal lobe epilepsy (MTLE), Permeability glycoprotein (P-gp), Multi-drug resistance 1 (MDR1), Multidrug resistance protein 1 (MRP1) 615 630 http://bcn.iums.ac.ir/browse.php?a_code=A-10-2554-3&slc_lang=en&sid=1 Mandeep Kaur kaurmandeephg@gmail.com 13700319475328460046663 13700319475328460046663 No Department of Anatomy, Institute of Medical Education and Research, Chandigarh, India. Tulika Gupta tulikag11@gmail.com 13700319475328460046664 13700319475328460046664 Yes Department of Anatomy, Institute of Medical Education and Research, Chandigarh, India. Mili Gupta miligupta8@yahoo.com 13700319475328460046665 13700319475328460046665 No Department of Biochemistry, Singh Judge Institute of Dental Sciences and Hospital, Panjab University, Chandigarh, India. Navneet Singla drnavi2007@yahoo.co.in 13700319475328460046666 13700319475328460046666 No Department of Neurosurgery, Institute of Medical Education and Research, Chandigarh, India. Parampreet S Kharbanda neuroparam@hotmail.com 13700319475328460046667 13700319475328460046667 No Department of Neurology, Institute of Medical Education and Research, Chandigarh, India. Yogender Singh Bansal yogendrabansal@hotmail.com 13700319475328460046668 13700319475328460046668 No Department of Forensic Medicine, Institute of Medical Education and Research, Chandigarh, India. Daisy Sahni daisy_sahni@rediffmail.com 13700319475328460046669 13700319475328460046669 No Department of Anatomy, Institute of Medical Education and Research, Chandigarh, India. Bishan Das Radotra bishanradotra@gmail.com 13700319475328460046670 13700319475328460046670 No Department of Histopathology, Institute of Medical Education and Research, Chandigarh, India. Sunil Kumar Gupta 13700319475328460046671 13700319475328460046671 No Department of Neurosurgery, Institute of Medical Education and Research, Chandigarh, India.