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Effects of a new neuroprotective agent KR-31378 on liver cytochrome P450s in male Sprague Dawley rats.

Abstract
The effects of KR-31378, a neuroprotective agent for ischemia-reperfusion damage, on liver microsomal cytochrome P450s (CYPs) were investigated in male Sprague Dawley rats. When rats were treated orally with KR-31378 for 7 consecutive days, CYP3A-selective erythromycin N-demethylase (ERDM) activity was significantly induced in a dose-dependent manner. In Western immunoblotting, CYP 3A proteins were clearly induced by treatment with KR-31378. Within 24 h after treatment with 80 mg/kg of KR-31378, ERDM activity was induced in liver microsomes in accompanied by induction of the level of CYP 3A proteins. The present results suggest that KR-31378 might modulate the expression of CYP 3A enzymes in humans.
AuthorsTae Cheon Jeong, Ji-Young Kim, Hye Young Ji, Dong Ha Lee, Sun-Ok Kim, Hong Lim, Sung Eun Yoo, Hye Suk Lee
JournalArchives of pharmacal research (Arch Pharm Res) Vol. 26 Issue 10 Pg. 800-4 (Oct 2003) ISSN: 0253-6269 [Print] Korea (South)
PMID14609126 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Guanidines
  • N''-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N'-benzylguanidine
  • Neuroprotective Agents
  • Pyrans
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2E1
  • Aryl Hydrocarbon Hydroxylases
  • CYP3A protein, human
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP2B1
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating
Topics
  • Administration, Oral
  • Animals
  • Aryl Hydrocarbon Hydroxylases (biosynthesis)
  • Blotting, Western
  • Cytochrome P-450 CYP1A1 (biosynthesis)
  • Cytochrome P-450 CYP2B1 (biosynthesis)
  • Cytochrome P-450 CYP2E1 (biosynthesis)
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System (biosynthesis, drug effects)
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Electrophoresis, Polyacrylamide Gel
  • Guanidines (administration & dosage, metabolism, pharmacokinetics)
  • Male
  • Microsomes, Liver (drug effects, enzymology)
  • Neuroprotective Agents (chemical synthesis, pharmacology)
  • Oxidoreductases, N-Demethylating (biosynthesis)
  • Pyrans (administration & dosage, metabolism, pharmacokinetics)
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

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