A comparison of the S(+) and R(-) enantiomers of 5-ethyl-5-phenylhydantoin as hypolipidemic agents in rodents.
An investigation of the effects of the S-(+) and R-(-) enantiomers of 5-ethyl-5-phenylhydantoin as hypolipidemic agents was undertaken. The serum cholesterol and triglyceride levels were reduced approximately 40% by either oral or i.p. administration at 20 mg/kg.day of either enantiomer. Both agents blocked activities of enzymes involved in the de novo synthetic pathway of lipids. Lipids removed from the blood compartment were not deposited into tissue, but appeared to be cleared from the body at a more rapid rate. Serum lipoproteins showed a reduction in cholesterol and triglyceride content of very low density (VLDL) and low density (LDL) fractions after two-week administration at 20 mg/kg.day and HDL cholesterol content was elevated particularly with the R-(-) enantiomer. The LD50 values of the enantiomers were 500 mg/kg i.p. or greater.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27514.
Maguire
J H
JH
Wong
O T
OT
Day
P A
PA
Alpin
R S
RS
D000284:Administration, Oral; D000818:Animals; D002784:Cholesterol / Q000097:blood; D005243:Feces / Q000032:analysis; D006827:Hydantoins / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D007536:Isomerism; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008617:Mephenytoin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood
D006827:Hydantoins; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; C014544:ethylphenylhydantoin; D002784:Cholesterol; D008617:Mephenytoin