Diphenylhydantoin substrate induced difference spectra: inhibition by other anticonvulsant drugs

The ability of five commonly used anticonvulsants to produce substrate induced difference specta was assessed. Only diphenylhydantoin (DPH) and phenobarbitone were observed to produce such spectra and were of Type I. Mean Ks values for DPH and phenobarbitone were 6.8 x 10(-5) and 4.0 x 10(-4)M, respectively. The anticonvulsants sulthiame, ethosuximide, sodium valproate and phenobarbitone exhibited inhibition of DPH substrate induced difference spectra to varying degrees. Analysis of data as in the classical enzyme/inhibitor models resulted in mean Ksi values for the four anticonvulsants of 1.3 x 10(-4), 0.53 x 10(-2), 3.0 x 10(-3), and 6.8 x 10(-3), respectively. Inhibition of DPH substrate induced difference spectra by sulthiame and phenobarbitone was strong and competitive. Inhibition by ethosuximide was weak and competitive, while sodium valproate's inhibition was weak and uncompetitive.