Hypoglycemic effect of S(-)-hydroxyhexamide, a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide.
A short-lasting hypoglycemic effect was observed when S(-)-hydroxyhexamide (S-HH), a major metabolite of acetohexamide, and its enantiomer R(+)-hydroxyhexamide (R-HH), were administered orally to rats. Since the reductive metabolism of acetohexamide is known to be reversible in rats, oral administration of R-HH may exhibit the hypoglycemic effect through the generation of acetohexamide. However, oral administration of R-HH to rabbits, in spite of their inability to oxidize R-HH to acetohexamide, caused a significant decrease and increase, respectively, of plasma glucose and insulin levels. Furthermore, both S-HH and R-HH were found to stimulate the secretion of insulin from hamster HIT T15 cells (pancreatic beta-cells). These results provide further evidence that both R-HH and S-HH exhibit a significant hypoglycemic effect.
Imamura
Y
Y
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan. yorishig@gpo.kumamoto-u.ac.jp
Sanai
K
K
Seri
K
K
Akita
H
H
D000092:Acetohexamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000032:analysis / Q000097:blood; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013997:Time Factors; D000096926:Benzenesulfonamides
D000092:Acetohexamide; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C020362:hydroxyhexamide; D000096926:Benzenesulfonamides