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.
Nagasawa
H T
HT
Medical Research Laboratories, Veterans Administration Medical Center, Minneapolis, MN 55417.
Elberling
J A
JA
Shirota
F N
FN
DeMaster
E G
EG
D000079:Acetaldehyde / Q000097:blood; D000427:Alcohol Deterrents; D000437:Alcoholism / Q000188:drug therapy; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002747:Chlorpropamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D007003:Hypoglycemia / Q000139:chemically induced; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000427:Alcohol Deterrents; D001786:Blood Glucose; C057478:N(1)-ethylchlorpropamide; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D002747:Chlorpropamide