The metabolism of 3-methyl-5-ethyl-5-phenylhydantoin (mephenytoin) to 5-ethyl-5-phenylhydantoin (Nirvanol) in mice in relation to anticonvulsant activity.
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/kh 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 Nivanol were 19.2 and 8.1 mug/g, respectively. The brain levels of mephenytoin fell to 5.8 mug/g and those of Nirvanol rose to 18.2 mug/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 fo mephenytoin and the later activity to Nirvanol.
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002849:Chromatography, Gas; D004597:Electroshock; D006827:Hydantoins / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D013997:Time Factors
D000927:Anticonvulsants; D006827:Hydantoins