A new hypoglycemic agent, midaglizole, blunts diabetic platelet aggregation: a possible role of alpha 2 blockade.
A newly developed alpha 2 blocker, midaglizole (DG-5128, 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate) has been shown to have a hypoglycemic action in healthy controls as well as in diabetics. Since human platelets are rich in alpha 2 receptors, the effects of midaglizole on platelet aggregation were investigated. In normal controls, ADP- or epinephrine-induced platelet aggregation was significantly inhibited 2 h after oral administration of 300 mg midaglizole. Midaglizole also suppressed diabetic platelet aggregation stimulated by 10 or 100 microM epinephrine and delayed the initiation of collagen-induced aggregation at 30 micrograms/ml. In vitro addition of midaglizole at 9 or 90 microM significantly inhibited epinephrine-induced platelet aggregation. Furthermore, long-term administration of midaglizole suppressed diabetic platelet aggregation induced by 0.5-1 microM ADP or 1 microM epinephrine. These results suggest that alpha 2 blockade not only blunts diabetic epinephrine-induced platelet aggregation but also affects ADP- or collagen-stimulated platelet aggregation, indicating that this alpha 2 blocker may offer a new approach to the treatment of diabetic microangiopathy.
Inaba
M
M
Department of Internal Medicine, Saitama Medical School, Japan.
Katayama
S
S
Kawazu
S
S
Suzuki
M
M
Negishi
K
K
Ishii
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; C032368:midaglizole