Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Jul;31(7):812-818.
doi: 10.1177/0269881116684338. Epub 2017 Jan 16.

Altering ethanol pharmacokinetics to treat alcohol use disorder: Can you teach an old dog new tricks?

Carolina L Haass-Koffler  1   2   3 , Fatemeh Akhlaghi  4 , Robert M Swift  1   5 , Lorenzo Leggio  2   3
Affiliations
Review

Altering ethanol pharmacokinetics to treat alcohol use disorder: Can you teach an old dog new tricks?

Carolina L Haass-Koffler et al. J Psychopharmacol. 2017 Jul.

Abstract

Disulfiram was the first pharmacotherapy approved to treat alcohol use disorder in the 1950s. Disulfiram alters ethanol pharmacokinetics and causes uncomfortable reactions (e.g. headache, tachycardia, nausea, flushing and hypotension) when alcohol is consumed. Subsequently, a better understanding of the neurobiological pathways involved in alcohol use disorder led to the development of other medications (e.g. naltrexone and acamprosate). These neurobiological-based medications act on alcohol use disorder-related phenotypes including craving, stress, and/or withdrawal. The original approach to treat alcohol use disorder, by altering ethanol pharmacokinetics has been much less investigated. Recent research on ethanol pharmacokinetics has shed light on the mechanisms of action underlying alcohol use disorder and how some medications that alter ethanol pharmacokinetics may be helpful in treating alcohol use disorder. This review summarizes and discusses the complex pharmacokinetics of ethanol, and proposes that altering ethanol pharmacokinetics via novel pharmacological approaches may be a viable approach to treat alcohol use disorder.

Keywords: Pharmacokinetics; alcohol use disorder; biobehavioral mechanisms; ethanol; human laboratory studies.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

Dr. Swift has received travel and honorarium from D&A Pharma, Lundbeck and consultant fees from CT Laboratories. The other authors report no biomedical financial interests or potential conflicts of interest. The other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1
Figure 1. Pharmacological approaches that target ethanol metabolism via ALDH inhibition
Non selective irreversible inhibition of ALDH (disulfiram) produces aversive side-effects. Selective ALDH2 reversible inhibition (ALDH2i) has been shown to prevent the increase of alcohol-induced rewarding dopamine release in brain, reduce cocaine-induced euphoria and inhibit anxiety-like behaviors.
Figure 2
Figure 2. Pharmacological approaches that can reduce ethanol cytotoxic effects
The pyridoxine-pyrrolidone carboxylate metadoxine can accelerate ethanol metabolism by increasing the activity of ALDH, inhibiting CYP2E1, and accelerating plasma and urinary clearance of ethanol. Metadoxine may also reduce cytotoxic effect of ethanol, reduce intoxication and improve recovery.
Figure 3
Figure 3. Pharmacological approaches that target the biphasic effects of ethanol
The α2-adrenergic antagonist idazoxan can reduce subjective effects secondary to ethanol intoxication.
See this image and copyright information in PMC

References

    1. Amir S. Brain and liver aldehyde dehydrogenase activity and voluntary ethanol consumption by rats: relations to strain, sex, and age. Psychopharmacology (Berl) 1978;57:97–102. - PubMed
    1. Anton RF, Drobes DJ, Voronin K, et al. Naltrexone effects on alcohol consumption in a clinical laboratory paradigm: temporal effects of drinking. Psychopharmacology (Berl) 2004;173:32–40. - PubMed
    1. Ardies CM, Lasker JM, Lieber CS. Characterization of the cytochrome P-450 monooxygenase system of hamster liver microsomes. Effects of prior treatment with ethanol and other xenobiotics. Biochem Pharmacol. 1987;36:3613–3619. - PubMed
    1. Arolfo MP, Overstreet DH, Yao L, et al. Suppression of heavy drinking and alcohol seeking by a selective ALDH-2 inhibitor. Alcohol Clin Exp Res. 2009;33:1935–1944. - PMC - PubMed
    1. Breslow RA, Dong C, White A. Prevalence of alcohol-interactive prescription medication use among current drinkers: United States, 1999 to 2010. Alcohol Clin Exp Res. 2015;39:371–379. - PMC - PubMed

Publication types