Disulfiramlike Actions Produced by Hypoglycemic Sulfonylurea Compounds

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Abstract
The object of this investigation was to study the mechanism of this action and especially to determine whether it results from the hypoglycemic action of the drugs. The possibility of an adrenergic blocking action was also explored. Two tests of disulfiram-like activity were used. In rats, doses of tolbutamide in the range of 65 to 250 mg/kg produced increased acetaldehyde (AcH) from 7.0 to 13.5 [mu]/ml higher than in controls given only ethanol. The vasodepressor phase of blood pressure responses in 5 cats injected with 30 mg/kg of AcH was deeper by an average of 16.4 mm Hg (p<.02), whereas this phase of response to epinephrine was unchanged in 5 cats by 200 mg/kg of tolbutamide. Insulin(5 [mu]/kg) did not change the vasodepressor response to either AcH or epinephrine (6 cats). However, a dose of glucose (0.5 to 1.0 g) sufficient to correct the hypoglycemia reversed the tolbutamide-induced potentiation of the hypotensive phase. A bradycardia of vagal origin occurred during the depressor phase of AcH after 200 mg of tolbutamide/kg but experiments with atropine indicated that this was not the cause of the greater fall. Chlorpropamide also was active in potentiating AcH vasodepression.