Description
CGP 7930 is a positive allosteric modulator of GABA
B receptors. It enhances GABA binding with a maximal effect of 143% compared to a GABA-only control in CHO cells membranes expressing the GABA
B(1b/2) receptor and enhances GABA binding to rat cortical membranes when used at a concentration of 30 μM. It is selective for GABA binding to heterodimeric GABA
B(1b/2) over monomeric GABA
B(1b) receptors. CGP 7930 potentiates the efficacy of the GABA
B receptor agonist baclofen in decreasing the spontaneous firing rate of dopaminergic neurons in the rat ventral tegmental area (VTA)
in vitro (EC
50 = 0.27 μM). It also potentiates the sedative-reducing effects induced by the GABA
B receptor agonists baclofen and γ-hydroxybutyric acid (GHB) in rats when administered at doses ranging from 10 to 170 mg/kg, effects that can be blocked by the GABA
B receptor antagonist SCH 50911. CGP 7930 reduces self-administration of nicotine, alcohol, and cocaine in rodent models. It suppresses the acquisition of alcohol drinking behavior in alcohol-naïve Sardinian alcohol-preferring rats over a five-day period when administered at doses ranging from 25 to 100 mg/kg and transiently reduces the maintenance of alcohol drinking behavior in alcohol-experienced rats at a dose of 100 mg/kg.
Biological Activity
Positive allosteric modulator of GABA B receptors. Increases the potency and efficacy of GABA at both native and recombinant GABA B receptors (EC 50 values are 5.37 and 4.60 μ M respectively) and enhances the inhibitory effect of the agonist L-baclofen in cultured cortical neurons. Reduces operant self-administration of ethanol in alcohol-preferring rats following i.p. administration.
