Opryshko V. Antioxidative modulatoon of pharmacological activity of analgesic drugs and anticonvulsants

Thesis is devoted to the experimental solution of a problem of medicamental pain therapy at raised convulsive brain readiness (experimental equivalents of an epilepsy), and also on application of antiepileptic drugs. It was established that among analgetics and anticonvulsants pharmacodynamic antagonism is observed which shows leveling of anticonvulsive activity of anticonvulsants by analgetics (tramadol, diclofenac sodium, ketoprofen, ketorolac) and reduction of analgesic action of analgetics (tramadol, paracetamol, diclofenac sodium, parecoxib, celecoxib, ketoprofen, ketorolac, analben, benzofurocaine) by antiepileptic drugs, thus "vicious circle" is formed. The mechanism of such phenomenon has been found out in neurophysiologic researches. It was established that convulsions, as well as pain stimulation, initiate oxidative stress development. It was shown that analgesic activity of analgetics is increased and its negative influence on anticonvulsive activity of anticonvulsants is leveled at combined action of analgetics (tramadol) together with antioxidants. On the other hand, the combination of anticonvulsants and antioxidants leads to increasing of antiparoxysmal activity of anticonvulsants. On the basis of pharmacological and toxicological researches the new combined preparation "Carbatril" in the form of tablets (carbamazepine 150 mg and thiotriazolin 100 mg).