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

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.

Alcohol withdrawal syndrome

“…Inhibitory and excitatory neurotransmitters in the brain balance neurochemicals. 6,7,9 Neurotransmitters initiate and transmit nerve conduction through the nervous system; alcohol consumption affects each one. 6,7,9 Thiamine (vitamin B-1) is a cofactor for synthesizing neurotransmitters, enhancing neuronal function, and converting carbohydrates into energy.…”

“…6,7,9 Neurotransmitters initiate and transmit nerve conduction through the nervous system; alcohol consumption affects each one. 6,7,9 Thiamine (vitamin B-1) is a cofactor for synthesizing neurotransmitters, enhancing neuronal function, and converting carbohydrates into energy. 10,11 Thiamine is not manufactured in the body and must be acquired from the diet.…”

“…Several mechanisms mediate AWS. Inhibitory and excitatory neurotransmitters in the brain balance neurochemicals 6,7,9. Neurotransmitters initiate and transmit nerve conduction through the nervous system; alcohol consumption affects each one 6,7,9…”

Potential Link Between Exercise and N-Methyl-D-Aspartate Glutamate Receptors in Alcohol Use Disorder: Implications for Therapeutic Strategies

“… 75 The neurotransmitters linked to reinforcing effects of alcohol are said to be endogenous opiates, GABA, serotonin, dopamine, and glutamate acting on NDMA receptors. 76 There have been numerous studies that found chronic ethanol exposure increases expression of NMDARs in the hippocampus; 77 , 78 medial orbitofrontal cortex; 77 agranular insular cortex; 79 nucleus accumbens core; central nucleus of amygdala; 80 and other parts of the central nervous system. 81 It is important to note this compensatory mechanism has been shown to proliferate NMDARs that deviate from the endogenous receptors.…”