Detail of "668-94-0"

Reference

Inhibition of microsomal phenytoin metabolism by nafimidone and related imidazoles

Inhibition of microsomal phenytoin metabolism by nafimidone and related imidazoles. Potency and structural considerations. Kapetanovic, I. M.; Kupferberg, H. J. (Preclin. Pharmacol. Sect., Natl. Inst. Neurol. Communicative Disorders and Stroke, Bethesda, MD 20205, USA). Drug Metab. Dispos., 13(4), 430-7 (English) 1985. CODEN: DMDSAI. ISSN: 0090-9556. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Nafimidone [64212-22-2] and other 1-imidazoles were potent inhibitors of phenytoin [57-41-0] p-hydroxylation in rat hepatic microsomes, being very effective even at submicromolar concns. The inhibitory potency of these 1-imidazoles was similar to that of SKF 525-A [62-68-0] and considerably greater than that obsd. for other imidazoles (4,5-diphenylimidazole [668-94-0], cimetidine [51481-61-9], metronidazole [443-48-1]), metyrapone [54-36-4], or other anticonvulsants. The effects of structural modification on the drug-metab. inhibitory activity were examd. Except at the 2-position on the imidazole, alkyl substitution increased the inhibitory potency, probably because of increased lipophilicity. Substitution at the 2-position caused marked diminution in inhibitory activity, possibly due to steric hindrance. The hydroxy analogs of nafimidone exhibited greater inhibitory activity than the corresponding keto compds. Furthermore, pretreatment of the rats with nafimidone resulted in greater Vmax values for both low affinity and high affinity metabolic sites.