CGP7930: A Positive Allosteric Modulator of the GABAB Receptor

Abstract

CGP7930 (3-(3′,5′-Di-tert-butyl-4′-hydroxy)phenyl-2,2-dimethylpropanol) is a positive allosteric modulator of the metabotropic GABA_B receptor. CGP7930 has been found to modulate the GABA_B receptor in the open, or high affinity, state increasing agonist affinity for the receptor and signal transduction efficacy following agonist stimulation. The GABA_B 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 GABA_B receptor by positive allosteric modulators may be able to regulate abuse of these drugs. Baclofen, the GABA_B 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.