Effect of a new hypoglycemic agent, A-4166 [(-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine], on postprandial blood glucose excursion: comparison with voglibose and glibenclamide

Biol Pharm Bull. 1997 Apr;20(4):354-9. doi: 10.1248/bpb.20.354.


(-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166) is a new nonsulfonylurea hypoglycemic agent that lowers blood glucose by stimulating insulin release. In the present study, we examined the effects of A-4166, voglibose (an alpha-glucosidase inhibitor), and glibenclamide (a sulfonylurea) on the postprandial glycemic increase in rats with or without diabetes mellitus. Oral administration of A-4166 (25-100 mg/kg) dose-dependently decreased blood glucose with a rapid onset and short duration in normal rats. On the other hand, glibenclamide (1-4 mg/kg) showed a slower onset of its hypoglycemic action, and voglibose (0.2 mg/kg) had no effect. In the case of postprandial glucose excursion, the carbohydrate-induced increase in blood glucose was reduced by oral administration of either A-4166 or voglibose without causing sustained hypoglycemia in both normal and neonatal streptozotocin-induced diabetic rats. However, the efficacy of voglibose varied with the type of carbohydrate load. Glibenclamide produced a prolonged decrease in blood glucose without any appreciable effect on the initial glucose excursion. After sucrose loading, plasma insulin levels during the initial 1 h were significantly higher in A-4166-treated rats than in control rats, while voglibose completely inhibited the insulin response to sucrose. In glibenclamide-treated rats, an augmented insulin response was not seen. In conclusion, unlike other hypoglycemic agents, A-4166 suppresses postprandial glucose excursions by stimulating the early phase of insulin secretion.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Glucose / analysis*
  • Cyclohexanes / pharmacology*
  • Diabetes Mellitus, Experimental / blood*
  • Enzyme Inhibitors / pharmacology
  • Glucose / administration & dosage
  • Glyburide / pharmacology
  • Hypoglycemic Agents / pharmacology*
  • Inositol / analogs & derivatives
  • Inositol / pharmacology
  • Insulin / blood
  • Male
  • Nateglinide
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacology
  • Postprandial Period*
  • Rats
  • Rats, Wistar
  • Sucrose / administration & dosage


  • Blood Glucose
  • Cyclohexanes
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Nateglinide
  • Phenylalanine
  • Inositol
  • Sucrose
  • Glucose
  • voglibose
  • Glyburide