Description
Mephenytoin is N-methylated at position 3 with an ethyl group replacing one of the phenyl substituents at position 5.
It is indicated for focal and jacksonian seizures in patients refractory to less toxic AEDs. Mephenytoin produces more sedation
than phenytoin and should be used only when safer drugs have failed, because it is associated with an increased incidence of
serious toxicities, such as severe rash, agranulocytosis, and hepatitis. Its N-desmethyl metabolite, 5-phenyl-
5-ethylhydantoin, contributes to both efficacy and toxicity for mephenytoin. The drug is no longer commercially available inside
but is still available outside the United States.
Originator
Mesantoin,Sandoz
Uses
rac-Mephenytoin is an anticonvulsant agent.
Definition
ChEBI: Mephenytoin is an imidazolidine-2,4-dione (hydantoin) in which the imidazolidine nucleus carries a methyl group at N-3 and has ethyl and phenyl substituents at C-5. An anticonvulsant, it is no longer available in the USA or the UK but is still studied largely because of its interesting hydroxylation polymorphism. It has a role as an anticonvulsant.
Manufacturing Process
23 parts sodium was dissolved in 300 parts of ethanol and added to 160 parts of 5-phenylcyanacetamide in 750 parts of ethanol. A mixture was cooled straight away and a sodium salt of amide precipitated as a white powder. 200 parts of ethyl iodide was added to this mixture and heated for 1.5 hours. The ethanol was distilled off, water was added to the residue and rapidly hardened oil precipitated. After recrystallization from ethanol, 5-ethyl-5- phenylacetamide afforded; MP: 116°C.
100 parts of sodium hydroxide was solved in 500 parts of water and added to
83 parts of bromine by cooling. 5-Ethyl-5-phenylacetamide was added to
above prepared mixture. It dissolved quickly, whereupon all mass was heated
some time, cooled and stood at room temperature some hours. Then a
solution of sodium bisulfite was added before the formed precipitate dissolved.
The reaction mixture was filtered, the filtrate was acidified to give rapidly
hardened oil. After recrystallization from ethanol 5-ethyl-3-methyl-5-phenylhydantoin was yielded as the bright needles; MP: 201°-202°C.
brand name
Mesantoin (Novartis).
Therapeutic Function
Anticonvulsant, Antiepileptic
Biological Activity
CYP2C19 substrate. Anticonvulsant.
Biochem/physiol Actions
CYP2B6 and CYP2C19 substrate; anticonvulsive, antiepileptic.
Side effects
Side effects, including rash, fever, and fatal blood dyscrasia, prevent the use as an anticonvulsant drug of first choice.
Safety Profile
Poison by ingestion and
intraperitoneal routes. Human systemic
effects by ingestion: somnolence,
hemorrhage, changes in teeth and
supporting structures. Human mutation data
reported. An experimental teratogen. An
FDA proprietary drug used as an
anticonvulsant. When heated to
decomposition it emits toxic fumes of NOx.
