Abstract

The subcellular distribution of 4-¹⁴C-diphenylhydantoin in cerebral cortex after injection into the cisterna magna of male Sprague-Dawley rats has been studied. Diphenylhydantoin readily penetrated into the cerebral cortex and was localized in the major subcellular fractions. The nuclear fraction and supernatant fluid contained the greatest quantity of radioactive drug 15 minutes after injection; the microsomal fraction contained the least. By 12 hours postinjection, the microsomal fraction had retained the drug to a greater extent; approximately 38% of the total radioactivity in the cerebral cortex was bound by these particles. The supernatant fluid contained about 44%, and the mitochondrial and nuclear fractions contained approximately 2% each. Binding of the drug by the microsomal and nuclear fractions was firm and could be released only upon alkaline hydrolysis. From the data presented, it appears that the microsomal fraction is the major binding site for diphenylhydantoin in the cerebral cortex.