Effect of oral hypoglycemic drugs on heart norepinephrine (NE) in rats and mice.
We studied the effect of oral hypoglycemic drugs on heart NE in normal and diabetic animals as a possible model for obtaining some insight into the mechanism for the alleged cardiotoxicity of these drugs in diabetic humans. The biguanides, but not the sulfonylureas, lowered NE in the hearts of rats and mice. Our results indicate this effect is not due to changes in blood glucose or a metabolite of the biguanides, but do not completely rule out an effect on biosynthesis or interference with the NE uptake pump in the adrenergic nerve endings. However, the data identify the biguanide portion  of the molecule to be the active moiety and suggest that an indirect toxic effect of the drug probably is involved.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008861:Microsomes / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010629:Phenformin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014044:Tolbutamide / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D014044:Tolbutamide; D010629:Phenformin; D009638:Norepinephrine