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Chemical systems for delivery of antiepileptic drugs to the central nervous system

, : Chemical systems for delivery of antiepileptic drugs to the central nervous system. Epilepsy Research 13(1): 1-16

The chemical delivery system (CDS) approach, a recently developed procedure conceived to enhance the specific central nervous system (CNS) uptake of drugs, has been applied to several antiepileptic agents. CDSs based on dihydropyridine<-->pyridinium salt type redox targetors, reversibly linked to the drug, were designed, synthesized and tested for some traditional (phenytoin, valproate) and potential (stiripentol) antiepileptic drugs, as well as some compounds (GABA, adenosine) with important roles in epileptogenesis. Physicochemical, in vitro stability, in vivo tissue distribution, activity and toxicity studies were performed for the new derivatives. The results of these investigations indicated that selected CDSs possessed properties required for delivering the drugs to the CNS. In vivo experiments indicated improved brain uptake and enhanced pharmacologic activity in some of the examined cases. On the other hand, no toxic side effects were registered during the studies. Properly developed CDSs could enhance the therapeutic indexes of the anticonvulsant drugs.


PMID: 1478193

DOI: 10.1016/0920-1211(92)90002-b

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