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Expert Opin Drug Discov. 2014 Nov;9(11):1307-17. doi: 10.1517/17460441.2014.956076. Epub 2014 Sep 8.

Targeting GABAB receptors for anti-abuse drug discovery.

Author information

1
Oregon Health & Science University, Veterans Affairs Medical Center, Department of Behavioral Neuroscience , 3710 SW US Veterans Hospital Rd, Portland, OR 97239 , USA +1 503 220 8262 Ext. 56674 ; +1 503 721 1029 ; phillipt@ohsu.edu.

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

PMID:
25195620
DOI:
10.1517/17460441.2014.956076
[Indexed for MEDLINE]

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