CGP7930: A Positive Allosteric Modulator of the GABAB Receptor

Authors

  • C. L. Adams,

    1. Department of Pharmaceutical Biology, Victorian College of Pharmacy, Monash University, Australia
    2. Howard Florey Institute, Parkville, Victoria, Australia
    Search for more papers by this author
  • A. J. Lawrence

    1. Howard Florey Institute, Parkville, Victoria, Australia
    2. Centre for Neuroscience, University of Melbourne, Victoria, Australia
    Search for more papers by this author

  • Conflict of interest: The authors have no conflict of interest.

Address correspondence and reprint requests to: Professor Andrew Lawrence, Howard Florey Institute, Royal Parade, Parkville, Vic 3010, Australia. E-mail: Andrew.Lawrence@florey.edu.au

ABSTRACT

CGP7930 (3-(3′,5′-Di-tert-butyl-4′-hydroxy)phenyl-2,2-dimethylpropanol) is a positive allosteric modulator of the metabotropic GABAB receptor. CGP7930 has been found to modulate the GABAB receptor in the open, or high affinity, state increasing agonist affinity for the receptor and signal transduction efficacy following agonist stimulation. The GABAB heteromeric subunit B2, involved in signal transduction but not ligand binding, seems to be the site of action of CGP7930 and similar allosteric modulators. When administered alone in naïve animals, CGP7930 acts as an anxiolytic in rodents without other overt behavioral effects and has also been demonstrated to reduce self-administration of nicotine, cocaine, or alcohol in rodents, suggesting that “fine tuning” of the GABAB receptor by positive allosteric modulators may be able to regulate abuse of these drugs. Baclofen, the GABAB agonist, is currently finding use in treating addiction and various other disorders, but this can result in off-target effects and tolerance. CGP7930 when co-administered with baclofen enhances its potency, which could in theory minimize deleterious effects. Further study of CGP7930 is required, but this compound, and others like it, holds potential in a clinical setting.

Ancillary