GABAB receptors as a therapeutic strategy in substance use disorders: Focus on positive allosteric modulators

@article{Filip2015GABABRA,
  title={GABAB receptors as a therapeutic strategy in substance use disorders: Focus on positive allosteric modulators},
  author={Małgorzata Filip and Małgorzata Frankowska and Anna Sadakierska-Chudy and Agata Suder and Łukasz Szumiec and Pawel Mierzejewski and Przemysław Bienkowski and Edmund Przegaliński and John F. Cryan},
  journal={Neuropharmacology},
  year={2015},
  volume={88},
  pages={36-47}
}
γ-Aminobutyric acid B (GABAB) receptors and their ligands are postulated as potential therapeutic targets for the treatment of several brain disorders, including drug dependence. Over the past fifteen years positive allosteric modulators (PAMs) have emerged that enhance the effects of GABA at GABAB receptors and which may have therapeutic effects similar to those of agonists but with superior side-effect profiles. This review summarizes current preclinical evidence supporting a role of GABAB… Expand
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Targeting the GABAB Receptor for the Treatment of Substance Use Disorder
TLDR
This chapter reviews the current preclinical research on the significance of central γ-amino butyric acid (GABA)B receptors in substance use disorder (SUD) and the SUD potential pharmacotherapy based on GABAB receptor ligands, and provides compelling preclinical evidence that GABAB receptors agonists and positive allosteric modulators may have efficacy in the treatment of SUD. Expand
Targeting GABAB receptors for anti-abuse drug discovery
TLDR
The more immediate development of baclofen as a therapeutic for alcohol use disorders may be of significant benefit to some individuals, and genetic and physiological differences are likely to contribute to individual responses to different therapeutic agents. Expand
GABAB Receptors and Drug Addiction: Psychostimulants and Other Drugs of Abuse.
TLDR
Preclinical research suggests that GABABR PAMs are emerging as promising candidates for the treatment of drug addiction, and more are needed, and compounds with better pharmacokinetics and fewer side effects are critically needed. Expand
[GABAB receptor as therapeutic target for drug addiction: from baclofen to positive allosteric modulators].
TLDR
Experimental and clinical data indicating the therapeutic potential of the GABAB receptor agonist, baclofen, in the treatment of alcohol use disorder and substance use disorder are summarized and GABAB PAMs may represent a major step forward in a GABAB receptors-based pharmacotherapy of AUD and SUD. Expand
Efficacy and side effects of baclofen and the novel GABAB receptor positive allosteric modulator CMPPE in animal models for alcohol and cocaine addiction
TLDR
Positive allosteric modulation of the GABAB receptor provides efficacy, and no observable side effects in relapse behavior whereas baclofen may cause, not only sedation, but also considerable impairment of food intake or metabolism, although targeting GABAB receptors may be effective in reducing certain aspects of addictive-like behavior. Expand
KK-92A, a novel GABAB receptor positive allosteric modulator, attenuates nicotine self-administration and cue-induced nicotine seeking in rats
TLDR
Results indicate that KK-92A is a selective GABABR PAM with efficacy in inhibition of the primary reinforcing and incentive motivational effects of nicotine, and attenuation of nicotine seeking, further confirming that GABA BR PAMs may be useful antismoking medications. Expand
Designing modulators of 5-hydroxytryptamine signaling to treat abuse disorders
TLDR
Based on the current evidence, the authors believe that BDNF, as a modulator of the serotonergic pathway, or 5-HT, as one of the modulators of the BDNF system, represent a valuable target to treat drug addiction, which may yield novel therapeutics in the future. Expand
Potential of Cannabinoid Receptor Ligands as Treatment for Substance Use Disorders
TLDR
Recent progress in research regarding the endocannabinoid systems, cannabis reward versus aversion, and the underlying receptor mechanisms is reviewed, and cannabinoid-based medication development for the treatment of SUDs is reviewed. Expand
Anticonvulsant effects of structurally diverse GABAB positive allosteric modulators in the DBA/2J audiogenic seizure test: Comparison to baclofen and utility as a pharmacodynamic screening model
TLDR
The results presented here suggest the DBA/2J mouse AGS test is a potentially useful screening model for detecting PD effects of GABA(B) PAMs and can provide an initial read-out on target-related motor side-effects. Expand
Neuroendocrine response to GABA-B receptor agonism in alcohol-dependent individuals: Results from a combined outpatient and human laboratory experiment
TLDR
Light is shed on the role of the GABAergic system and GABA‐B receptors in the shared neurobiology of alcohol‐, feeding‐, and stress‐related behaviors as well as on the pharmacological manipulation of these receptors by orthosteric agonists and positive allosteric modulators. Expand
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