topiramate and coriaria-lactone

The earliest records of traditional Chinese medicine (TCM) prevention and treatment of epilepsy dated back to famous "Huang Di Nei Jing." TCM "spasmolytic powder" (equal-ratio compatibility of scorpion and centipede) is a famous prescription which was recognized as a useful add-on drug for refractory epilepsy in clinical observations. Multidrug resistance gene (mdr1) product Pgp overexpression in blood-brain barrier and blood-cerebrospinal fluid barrier is well recognized as the drug resistance mechanism of refractory epilepsy. Here, we established the drug-resistant epilepsy Sprague-Dawley rat model induced by Coriaria Lactone and treated these rats with topiramate and verapamil and low dose, middle dose, and high dose of spasmolytic powder by intragastric administration for 1 week. Electroencephalogram, real-time PCR, and immunohistochemistry were respectively used to detect epileptic discharge frequencies and amplitudes and expression of mdrl mRNA and Pgp on hippocampus and temporal lobe of rats. The results showed that the seizure decreases significantly in the high- and middle-dose groups of spasmolytic powder and topiramate group; in addition, mdr1 mRNA and Pgp expressions on hippocampus and temporal lobe of these drug intervention groups were significantly less than the model group (P < 0.05). These findings indicate that inhibition of intracephalic Pgp expression is possibly one of mechanisms of spasmolytic powder treating refractory epilepsy.

Topics: Animals; Anticonvulsants; Arthropods; ATP Binding Cassette Transporter, Subfamily B, Member 1; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Electroencephalography; Epilepsy; Fructose; Hippocampus; Kindling, Neurologic; Lactones; Male; Medicine, Chinese Traditional; Rats; Rats, Sprague-Dawley; Temporal Lobe; Tissue Extracts; Topiramate; Verapamil

Overexpression of the multiple drug resistance gene 1 (MDR1) was quantified in brain tissue from Coriaria lactone (CL)-kindled Sprague-Dawley (SD) rats after treatment with lamotrigine (LTG) or topiramate (TPM) and compared with that found in rats treated with carbamazepine (CBZ) and valproate (VPA).. Twenty-five CL-kindled SD rats were randomized into five groups (n = 5 for each group) to receive once-daily feeding of CBZ, VPA, TPM, and LTG as the monotherapy equivalent of maximum human adult dosage, or normal saline (NS control) for 1 month. The expression of P-gp in brain tissues of all rats was quantified by using an image analysis and measuring system (Image Pro-plus 4.0). Mean area and mean integrated optical density (mean IOD) of P-gp expression were calculated. In addition, the changes in seizure severity were analyzed via video-camera monitoring.. A significant decrease in the number and duration of seizures with antiepileptic drug (AED) treatment was observed in the TPM and LTG groups. The mean area and mean IOD of P-gp expression were highest in the CBZ group and next highest in the VPA group; much lower values were measured in the TPM and LTG groups, and the lowest in the NS control group (p < 0.05).. TPM and LTG significantly inhibited seizures in this CL model. The expression of P-gp was not significantly increased by TPM or LTG treatment in this study.

Topics: Animals; Anticonvulsants; ATP Binding Cassette Transporter, Subfamily B, Member 1; Brain; Carbamazepine; Disease Models, Animal; Drug Resistance; Epilepsy, Temporal Lobe; Fructose; Gene Expression; Genes, MDR; Humans; Immunohistochemistry; Kindling, Neurologic; Lactones; Lamotrigine; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Topiramate; Triazines; Valproic Acid