Effects of aldehyde dehydrogenase inhibitors on hexobarbital sensitivity and neuroamine metabolism in rat brain.
Several authors have found that the aldehyde dehydrogenase (ALDH) inhibitor, disulfiram, prolongs hexobarbital-induced anaesthesia. It was suggested that this effect was caused by an alteration of the serotonergic system in brain, mediated by elevated levels of biogenic aldehydes. In the present study, disulfiram (300 mg/kg) was found to cause a 4-fold prolongation of hexobarbital-induced anaesthesia, while coprine (another potent ALDH-inhibitor) had no effect. This strongly suggested that biogenic aldehydes were not involved in this effect of disulfiram. The hexobarbital concentration in brain, at the electroencephalogram (EEG) criteria used for measuring hexobarbital sensitivity, was unaffected in rats given 75-300 mg/kg disulfiram, indicating that factors other than an increased brain hexobarbital sensitivity were responsible for the prolonged anaesthesia. Also 10-100 mg/kg coprine did not affect hexobarbital sensitivity measured this way. No alteration of the dopamine level in brain was found in rats given disulfiram, and in both disulfiram- and coprine-treated rats, similar changes in the serotonergic system were found. However, the level of norepinephrine was decreased in brains of disulfiram-treated rats, but it was unaffected by coprine. Thus, norepinephrine may have been involved in the prolongation of hexobarbital-induced anaesthesia caused by disulfiram.
D000445:Aldehyde Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001679:Biogenic Amines / Q000032:analysis*; D001923:Brain Chemistry / Q000187:drug effects*; D004221:Disulfiram / Q000008:administration & dosage*; D004298:Dopamine / Q000032:analysis; D004347:Drug Interactions; D005973:Glutamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006591:Hexobarbital / Q000008:administration & dosage*; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008297:Male; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis
D001679:Biogenic Amines; D005973:Glutamine; C014423:coprine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D006591:Hexobarbital; D000445:Aldehyde Oxidoreductases; D004221:Disulfiram; D004298:Dopamine; D009638:Norepinephrine