IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
STRUCTURES PHENYTOIN- AND TRIMETHADIONE- ANALOGS WITH ANTICONVULSANT ACTIVITY.
Autor/es:
ANDREA ENRIQUE; VALENTINA PASTORE; LUIS BRUNO BLANCH
Reunión:
Congreso; Academy of Sciences for the Developing World/BioVisionAlezandria.NXT 2012 (TWAS/BVA.NXT 2012) Program; 2012
Resumen:
STRUCTURES Phenytoin- and trimethadione- analogs WITH  anticonvulsant activity.   Andrea V. Enrique, Valentina Pastore & Luis E. Bruno Blanch.   Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata (UNLP). 47 & 115, La Plata (B1900AJI), Buenos Aires, Argentina. Phone: 542214235333 ext. 41.   The lack of efficacy and the large number of adverse effects who have AEDs available today justify the search for new anticonvulsant agents. In this work we present the biological evaluation of anticonvulsant activity of heterocyclic phenytoin- and trimethadione- analogs designed and synthesized for this purpose. Phenytoin is a widely used drug in the treatment of epilepsy. It achieves control of different types of crisis, but it also causes a wide-range of side reactions such as drowsiness, digestive disorders, gingival hyperplasia, lupus erythematosus, cutaneous, agranulocytosis, hepatotoxicity and osteomalacia among others(1) .Trimethadione is effective in absence seizures but is no longer a drug of choice due to the high incidence of teratogenic effects that occurs among other undesirable effects (2) . We relied on these structures, on which we performed bioisosteric replacements in order to preserve or enhance the biological activity and achieve a reduction in adverse effects. We present the results of pharmacological evaluation of rigid 5-member heterocyclic compounds  with 3 different heteroatoms (N-1, 2, 3-oxatiazolidin-4-one-2 ,2-dioxides).We have also studied the activity of some synthesis intermediates α-hydroxy amides. The tests were performed according to stage I of the Antiepileptic Drug Development (ADD) Program from the National Institute of Health (NIH) (USA) (3) using MES and PTZ test for the evaluation of anticonvulsant activity and rotorod test for the evaluation of neurotoxic effects. All the compounds tested were classified as Class I of NIH ADD Program, i.e. they present anticonvulsant activity at doses less than or equal to 100 mg / kg with no evidence of neurotoxic effects at the same dose.   (1)Simon Shorvon Handbook of Epilepsy Treatment, Blackwell Science Ltd., London, 2000. (2)Shepard T. et al. Catalog of teratogenic agents. The Johns Hopkins University Press. Eleventh Edition. 2004. (3)Porter et al. Antiepileptic Drug Development Program. Cleve. Clin. Q. 1984, Summer;51(2):293-305.