Identification of the metabolites of a new hypoglycaemic agent, midaglizole, in dogs.
1. The metabolism of a new hypoglycaemic agent, midaglizole, was studied. Six major metabolites were isolated from the urine of dogs dosed with 14C-midaglizole. The structures of these metabolites were elucidated by n.m.r., i.r., u.v. and mass spectrometry, and confirmed by comparison with synthesized authentic samples. 2. For midaglizole, oxidation on the imidazoline ring and subsequent ring-opening were the major metabolic pathways in dogs. 3. Two metabolites, namely, the imidazole analogue (M-I) and amidine analogue (M-III), had hypoglycaemic activity.
Drug Metabolism Research Center, Daiichi Seiyaku Co., Ltd, Tokyo, Japan.
M
M
Nakaoka
H
H
Hakusui
D000818:Animals; D001711:Biotransformation; D001786:Blood Glucose / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004285:Dogs; D007004:Hypoglycemic Agents / Q000378:metabolism* / Q000652:urine; D007093:Imidazoles / Q000378:metabolism* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007093:Imidazoles; C032368:midaglizole