The membrane stabilizing activity of β-adrenoceptor ligands: Quantitative evaluation of the interaction of phenoxypropanolamines with the [ 3H]batrachotoxinin a 20-α-benzoate binding site on voltage-sensitive sodium channels in rat brain

Abstract

The interaction of 12 phenoxypropanolamines, all ligands with high affinity towards β-adrenoceptors, with the [ 3H]batrachotoxinin A 20-α-benzoate ([ 3H]BTX-B) binding site on voltage-sensitive sodium channels in a rat brain synaptosomal preparation, was studied as a measure for local anaesthetic activity. All derivatives are capable of displacing [ 3H]BTX-B from its specific binding site, penbutolol displaying the highest affinity. Multiple regression analyses were performed, correlating biological activity (p K i values) with physicocheraical parameters. Lipophilicity is of prime importance in the established regression equations, but steric factors are relevant as well. Comparisons were made with analogous equations relating β 1- and β 2-adrenoceptor affinity with physicochemical parameters, leading to the conclusion that “cardioselective” β-adrenoceptor ligands appear to have fewer membrane stabilizing properties.