SLC Neurotransmitter Transporters as Therapeutic Targets for Alcohol Use Disorder: A Narrative Review

Alcohol Clin Exp Res. 2020 Oct;44(10):1965-1976. doi: 10.1111/acer.14445. Epub 2020 Sep 20.

Abstract

Alcohol use disorder (AUD) is 1 of the most prevalent of all substance use disorders and contributes significantly to global disease burden. Despite its prevalence, <10% of individuals with AUD receive treatment. A significant barrier to receiving treatment is a lack of effective pharmacotherapies. While 3 medications have been approved by the FDA for AUD (disulfiram, acamprosate, naltrexone), their efficacy remains low. Furthermore, a number of undesirable side effects associated with these drugs further reduce patient compliance. Thus, research into new effective pharmacotherapies for AUD is warranted. Due to their involvement in regulating synaptic neurotransmitter levels, solute carrier (SLC) transporters could be targeted for developing effective treatment strategies for AUD. Indeed, a number of studies have shown beneficial reductions in alcohol consumption through the use of drugs that target transporters of dopamine, serotonin, glutamate, glycine, and GABA. The purpose of this narrative review is to summarize preclinical and clinical studies from the last 2 decades targeting SLC neurotransmitter transporters for the treatment of AUD. Limitations, as well as future directions for expanding this field, are also discussed.

Keywords: Alcohol; Alcohol Use Disorder; Neurotransmitter Transporters; Neurotransmitters; SLC Transporters.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alcoholism / drug therapy*
  • Amino Acid Transport System X-AG / metabolism
  • Amino Acid Transport System X-AG / physiology
  • Animals
  • Dopamine / metabolism
  • Dopamine / physiology
  • GABA Plasma Membrane Transport Proteins / metabolism
  • GABA Plasma Membrane Transport Proteins / physiology
  • Glycine Plasma Membrane Transport Proteins / drug effects
  • Glycine Plasma Membrane Transport Proteins / metabolism
  • Glycine Plasma Membrane Transport Proteins / physiology
  • Humans
  • Neurotransmitter Agents / metabolism*
  • Neurotransmitter Agents / physiology
  • Serotonin / metabolism
  • Serotonin / physiology
  • Solute Carrier Proteins / drug effects*
  • Solute Carrier Proteins / metabolism
  • Solute Carrier Proteins / physiology

Substances

  • Amino Acid Transport System X-AG
  • GABA Plasma Membrane Transport Proteins
  • Glycine Plasma Membrane Transport Proteins
  • Neurotransmitter Agents
  • Solute Carrier Proteins
  • Serotonin
  • Dopamine