Abstract
Mephenytoin (3-methyl-5-ethyl-5-phenylhydantoin) is metabolized to Nirvanol (5-ethyl-5-phenylhydantoin). Both compounds block the hind leg tonic extensor phase of the Maximal Electroshock Seizure (M.E.S.) Test in mice. The M.E.S. ED50 of mephenytoin is 42 mg/kg at 30 min and 35 mg/kg at 2 hr after ip administration. The M.E.S. ED50 for Nirvanol at 30 min and 2 hr was 23 and 30 mg/kg, respectively. Brain and plasma levels of mephenytoin and Nirvanol were determined by gas-liquid chromatography after ip administration of 40 mg of mephenytoin per kg. At 30 min the brain levels of mephenytoin and Nirvanol were 19.2 and 8.1 µg/g, respectively. The brain levels of mephenytoin fell to 5.8 µg/g and those of Nirvanol rose to 18.2 µg/g at 2 hr. The total molar concentration of mephenytoin and Nirvanol, however, did not change more than 10% during the 2-hr period. Although the anticonvulsant activity of mephenytoin did not vary greatly during 2 hr after administration, the early activity is due in major part to mephenytoin and the later activity to Nirvanol.
Footnotes
- Received October 11, 1974.
- Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics
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