Increased Brain Serotonin Rather Than Increased Blood Acetaldehyde as a Common Denominator Behind Alleged Disulfiram-Like Reactions

  title={Increased Brain Serotonin Rather Than Increased Blood Acetaldehyde as a Common Denominator Behind Alleged Disulfiram-Like Reactions},
  author={Petros N. Karamanakos and Periklis Pappas and Vasiliki Boumba and Marios Marselos},
  journal={International Journal of Toxicology},
  pages={248 - 255}
Several pharmaceutical agents are known to produce ethanol intolerance, which is often depicted as disulfiram-like reaction. As in the case with disulfiram, the underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the hepatic aldehyde dehydrogenases, albeit this has not been confirmed in all cases by blood acetaldehyde measurements. Herein, cefamandole, cotrimoxazole, griseofulvin, procarbazine, and propranolol, which are reported to produce… 


Pharmaceutical Agents Known to Produce Disulfiram-Like Reaction: Effects on Hepatic Ethanol Metabolism and Brain Monoamines
The ethanol intolerance produced by these agents, either aldehyde dehydrogenase is inhibited or not, could be the result of a “toxic serotonin syndrome,” as in the case of the concomitant use of serotonin-active medications.
The Alcohol Intolerance Produced by Isoniazid Is Not Due to a Disulfiram-Like Reaction Despite Aldehyde Dehydrogenase Inhibition
Despite inhibition of the hepatic ALDH, ISO did not result in elevated blood acetaldehyde levels after ETH administration, probably due to the induction of cytochrome P450 2E1 which theoretically leads to an increased elimination rate of acetaldehyde preventing its accumulation.
Investigations on the ethanol-induced flushing reaction: effects of propranolol and dipyridamole on acetaldehyde and prostacyclin metabolism.
The results strongly suggest the possibility of producing a deterrent effect on the consumption of alcohol by using propranolol or dipyridamole, in contrast to disulfiram, which could potentially induce the flushing reaction in humans in the presence of low acetaldehyde concentrations.
The mechanism of alcohol intolerance produced by various therapeutic agents.
The results suggest that the so-called "disulfiram-reaction" is mediated mainly, but not exclusively, by inhibition of the low-Km ALDH.
Subcellular Localization of Acetaldehyde Oxidation in Liver a
  • H. Weiner
  • Chemistry, Medicine
    Annals of the New York Academy of Sciences
  • 1987
This article will not focus on any of the physiological or pharmacological effects of acetaldehyde, but only on its subcellular metabolism; an article in 1985 reviews many of those aspects of the p r ~ b l e m ~ While ethanol oxidizing enzymes are primarily localized in liver, those involved in acetaldehyde oxidation are ubiquitous to the body.
The effect of disulfiram on the aldehyde dehydrogenases of sheep liver.
  • T. Kitson
  • Chemistry, Medicine
    The Biochemical journal
  • 1975
It was shown that the mixed disulphide, Et2N-CS-SS- CH2-CH2-Ch2OH, strongly inhibits aldehyde dehydrogenase and the inhibitory effect of diethyldithiocarbamate in vitro is due mainly to contamination by disulfiram.
Disulfiram‐Cotrimoxazole Reaction
The disulfiram‐ethanol reaction is a well‐known clinical phenomenon occurring as a result of acetaldehyde accumulation in the blood. Symptoms usually begin within 5–15 minutes after ingestion of
Acetaldehyde as a substrate for ethanol-inducible cytochrome P450 (CYP2E1).
The results indicate that CYP2E1 is an aldehyde oxidase and thus metabolizes both ethanol and its primary oxidation product, although other water soluble products were also formed as evidenced from incubations with [1,2-14C]acetaldehyde.
Disulfiram-like reaction to certain cephalosporins.
Patients experiencing these often frightening disulfiram-type reactions seldom need specific treatment; however, it is mandatory to strongly caution patients not to consume alcoholic beverages for a few days after treatment with these cephalosporins.
p-Nitrophenol hydroxylation. A microsomal oxidation which is highly inducible by ethanol.
P-nitrophenol may be an extremely useful substrate for the study of changes in drug-metabolizing activity induced by ethanol treatment, and in isolated microsomes, rates of p-nitrocatechol hydroxylation were increased 6-fold after chronic ethanol treatment.