Studies of midaglizole (DG-5128). A new type of oral hypoglycemic drug in healthy subjects.
Midaglizole (DG-5128), 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate, is a novel alpha 2-adrenoceptor antagonist. Its effects on plasma glucose, immunoreactive insulin (IRI), and immunoreactive glucagon (IRG) in healthy male volunteers were investigated. Volunteers received single oral administrations of midaglizole (150-500 mg), multiple increasing oral administration on 3 separate days (150-300 mg 3 times daily), or successive daily oral administration for 1 wk (200 mg 3 times daily). The hypoglycemic action of midaglizole was observed within 0.5-1.0 h after its administration and thereafter for 5 h. The maximum hypoglycemic effect was found 1.0-1.5 h after administration. Midaglizole decreased postprandial hyperglycemia in a dose-dependent manner. In the fasting state, midaglizole significantly increased IRI secretion and suppressed IRG secretion. Midaglizole inhibited epinephrine-induced platelet aggregation after successive administration for 1 wk (200 mg 3 times daily). The plasma half-life of midaglizole was only 3 h, and the drug was rapidly excreted into the urine and feces, with greater than 80% in its unchanged form, within 24 h. Midaglizole did not affect the results of any clinical or laboratory tests performed. Our data indicate that midaglizole is a possible hypoglycemic agent. Further clinical investigations are required to confirm its effects on diabetes mellitus.
D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007093:Imidazoles; D007328:Insulin; C032368:midaglizole; D005934:Glucagon