STUDY OF THE PHARMACOLOGICAL EFFECTS AND TOXICITY OF OXCARBAZEPINE
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Oxacarbazepine (OXC) is a new antiepileptic drug structurally related to carbamazepine. It has shown a powerful protective effect against generalized tonic-clonic seizures with better tolerability and fewer side effects. This study was designed to detect changes in the level of neurotransmitters in different brain regions of rats with chemically-induced epilepsy pretreated by oxcarbazepine for 4 weeks compared to control epileptic and normal rats. Biochemical and the histopathological changes which could occur after prolonged use of oxcarbazepine in liver and kidney of these rats were also explored. Oxcarbazepine treatment abolished all phases of major generalized tonic-clonic chemically-induced seizures. Oxcarbazepine significantly reduced the concentration of dopamine and noradrenaline and increased GABA concentration in all tested brain regions of treated -rats. Oxcarbazepine treatment insignificantly alter biochemical parameters related to liver functions in the form of slight elevation of alkaline phosphatase and transaminase enzymes activities. However, Oxcarbazepine induced a significant hyponatremia and insignificant changes in serum creatinine and blood urea. Similarly, histopathological studies of oxcarbazepine treated rats revealed some minor changes such as dilatation and congestion of the central vein and blood sinusoids of the liver and glomerular hypercellularity with hyaline deposites and dilated cortical tubules in the kidney. In conclusion, oxcarbazepine could be used effectively and safely as a monotherapy in epilepsy. However, liver and kidney functions and serum electrolytes sould be monitored on prolonged use.