Abstract
Considering the importance of hydantoin derivatives in treatment of status epilepticus, four 5-phen- ylhydantoins, whose lipophilicities were estimated to be similar to that of phenytoin, were synthesized. Evaluation of their anticonvulsant activities was performed on rats by subcutaneous pentylenetetrazol seizure test and intravenous pentylenetetrazol threshold test, and spontaneous locomo- tor activity test was used to assess possible sedative effects. X-ray analysis of three compounds suggested that certain analogies might be drawn between interactions in crystal packing and biological interactions responsible for their anticonvulsant activity. It was found that 5-ethyl-5-phenyl- 3-propylhydantoin exhibits the most favorable pharmaco- logical properties among the synthesized compounds, i.e., anticonvulsant activity comparable to phenytoin with lower liability for induction of sedation in rats.
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