Inhibition of baclofen binding to rat cerebellar membranes by phaclofen, saclofen, 3-aminopropylphosphonic acid and related GABAB receptor antagonists.

The inhibition of the binding of the GABAB agonist 3H-baclofen to rat cerebellar membranes by some sulfonic and phosphonic acid analogues of GABA has been studied. These analogues have been shown to act as GABAB antagonists in the rat cortical wedge and the guinea-pig isolated ileum preparations. The order of potency of phaclofen (IC50 118 microM), 2-hydroxysaclofen (IC50 5.1 microM) and saclofen (IC50 7.8 microM) as inhibitors of 3H-baclofen binding was similar to the order of potency of these compounds as GABAB antagonists, whereas 3-aminopropylphosphonic acid (IC50 1.5 microM) and 4-aminobutyl-phosphonic acid (IC50 3.9 microM) were much more potent than anticipated from their relatively weak GABAB antagonist actions. These results indicate that inhibition of 3H-baclofen binding to rat cerebellar membranes does not reflect antagonist activity at GABAB receptors seen in the rat cortical wedge preparation or the guinea-pig isolated ileum preparation. This may indicate a heterogeneity of GABAB binding and receptor sites.