Disulfiram-ethanol reaction in the rat. 1. Blood alcohol, acetaldehyde, and liver aldehyde dehydrogenase relationships.
Studies were carried out to determine whether the disulfiram-ethanol reaction (DER) in the rat could be correlated with blood acetaldehyde, ethanol, and liver aldehyde dehydrogenase (ALDH) inhibition. Both hypothermia and hypotension were used as indices of the DER. Female Sprague-Dawley rats were given disulfiram (DSF) (100 mg/kg, i.p.) and low and high liver ALDH determined. No effect on high Km ALDH was found. Inhibition of low Km ALDH was dependent on DSF pretreatment time, with significant inhibition observed at 6, 8, and 12 hr following DSF. In rats receiving ethanol only, maximal blood ethanol was reached within 120 min. Blood acetaldehyde was almost undetectable. No change in rat core temperature was observed. In rats pretreated with DSF (100 mg/kg, i.p.) 8 hr before ethanol challenge (1 g/kg, i.p.), a marked increase in blood acetaldehyde was found and remained elevated throughout the temperature and blood pressure monitoring period. Blood ethanol reached a maximum within 90 min and then declined. Maximal hypothermia and hypotension occurred 120 min after ethanol. The administration of the dopamine receptor blocker pimozide (0.5 mg/kg, i.p.) 60 min before ethanol challenge, attenuated the hypothermia and hypotension. Pimozide was effective when given either 60 min before ethanol or 30 min after ethanol. The onset and duration of hypothermia and hypotension during the DER appears to follow the rise and fall of blood ethanol but not blood acetaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)
D000079:Acetaldehyde / Q000097:blood*; D000444:Aldehyde Dehydrogenase / Q000097:blood*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004221:Disulfiram / Q000008:administration & dosage*; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D008099:Liver / Q000201:enzymology*; D010868:Pimozide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D010868:Pimozide; D000431:Ethanol; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D004221:Disulfiram