Targeting GABA_B receptors for anti-abuse drug discovery

Abstract

Introduction: There is increasing evidence encouraging the development of drugs that positively modulate the γ-aminobutyric acid type B (GABA_B) receptor for combating addiction. Compounds that target GABA_B receptors are unique as anti-abuse therapies because of their impact against multiple addictive drugs.

Areas covered: The authors present the basic information concerning the drug actions of GABA and GABA_B receptor orthosteric agonists and positive allosteric modulators (PAM). Furthermore, they discuss several recent excellent reviews and newer results pertaining to GABA_B receptor drug effects on responses to and self-administration of: alcohol (ethanol), nicotine, cocaine, (meth)amphetamine, and opioids. Preclinical and clinical data are considered.

Expert opinion: Clinical data exist only for baclofen and mostly for alcohol use disorders. Additional trials are needed, but effects are promising. Whether PAMs, given alone or in combination with a direct GABA_B receptor agonist, will be clinically effective and have fewer side effects requires investigation. The sedative effects of baclofen, a Food and Drug Administration (FDA)-approved drug, become less severe over time. Based on existing data, baclofen is well-tolerated. However, genetic and physiological differences are likely to contribute to individual responses to different therapeutic agents. The more immediate development of baclofen as a therapeutic for alcohol use disorders may be of significant benefit to some individuals.

Keywords::

• addiction
• alcohol
• amphetamine
• baclofen
• cocaine
• ethanol
• methamphetamine
• nicotine
• opioid
• positive allosteric modulator

Notes

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