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 Paweł Mierzejewski and Przemysław Bieńkowski and Edmund Przegaliński and John F. Cryan},
  journal={Neuropharmacology},
  year={2015},
  volume={88},
  pages={36-47}
}

Figures and Tables from this paper

Targeting GABAB receptors for anti-abuse drug discovery

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.

GABAB Receptors and Drug Addiction: Psychostimulants and Other Drugs of Abuse.

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.

[GABAB receptor as therapeutic target for drug addiction: from baclofen to positive allosteric modulators].

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.

KK-92A, a novel GABAB receptor positive allosteric modulator, attenuates nicotine self-administration and cue-induced nicotine seeking in rats

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.

Designing modulators of 5-hydroxytryptamine signaling to treat abuse disorders

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.

Potential of Cannabinoid Receptor Ligands as Treatment for Substance Use Disorders

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.

Activation of the γ-Aminobutyric Acid Type B (GABA(B)) Receptor by Agonists and Positive Allosteric Modulators.

The recent report of the X-ray structure of the GABA(B) receptor with bound agonists and antagonists provides new insights for the development of compounds that bind the orthosteric site of this receptor.
...

References

SHOWING 1-10 OF 164 REFERENCES

GABAB receptors in addiction and its treatment.

Allosteric Modulators of GABAB Receptors: Mechanism of Action and Therapeutic Perspective

It is shown that, as expected, these molecules have more pronounced in vivo responses and less side effects than pure agonists, offering new potential therapeutic applications for this new class of GABAB ligands.

Chemistry and pharmacology of GABAB receptor ligands.

The GABAB Receptor-Positive Modulator GS39783 and the GABAB Receptor Agonist Baclofen Attenuate the Reward-Facilitating Effects of Cocaine: Intracranial Self-Stimulation Studies in the Rat

Assessment of the ability of the novel GABAB-positive modulator GS39873 or baclofen to modulate the behavioral effects of cocaine strongly suggest that activation of GABAB receptors attenuates the rewarding effects of acute cocaine.

GABAB receptors in reward processes.

Evaluation of the anxiolytic-like profile of the GABAB receptor positive modulator CGP7930 in rodents

GABA(B) receptors in drug addiction.

The present review summarizes the contribution of GABA(B) receptors to the rewarding, locomotor and discriminative stimulus properties of drugs of abuse and their withdrawal symptoms in laboratory animals.

GABAB Receptor-Positive Modulators: Enhancement of GABAB Receptor Agonist Effects In Vivo

Examining the in vivo positive modulatory properties of the GABAB receptor-positive modulators provides evidence that CGP7930 and rac-BHFF act in vivo as positive modulators at GABAB receptors mediating loss of righting, but not at neurons mediating hypothermia.

GABAB receptors and depression. Current status.

Effects of GABAB receptor ligands in animal tests of depression and anxiety.

The results indicate that differential manipulation of GABA(B) receptors can modify behaviors relevant to depression and anxiety.
...