A nonhypoglycemic chlorpropamide analog that inhibits aldehyde dehydrogenase

Chlorpropamide (CP), a sulfonylurea-type oral hypoglycemic agent, is known to provoke a flushing reaction reminiscent of the disulfiram-ethanol reaction in certain individuals. This is manifested in rodents by an increase in blood acetaldehyde levels after ethanol administration. When the sulfonamide N1-nitrogen of CP was substituted with an ethyl group, the product, N1-ethylchlorpropamide, was found to be three times as active as CP in raising ethanol-derived blood acetaldehyde. However, whereas CP lowered fasting blood glucose in rats measured over 6 h, N1-ethylchlorpropamide was devoid of hypoglycemic activity, suggesting that the latter might be potentially useful as an alcohol deterrent agent.