The membrane stabilizing activity of beta-adrenoceptor ligands. Quantitative evaluation of the interaction of phenoxypropanolamines with the [3H]batrachotoxinin A 20-alpha-benzoate binding site on voltage-sensitive sodium channels in rat brain.

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Ijzerman AP, Nagesser A, Garritsen A

Biochem Pharmacol. 1987 Dec 15;36(24):4239-44.

PubMed ID

2446632 [ View in PubMed

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Abstract

The interaction of 12 phenoxypropanolamines, all ligands with high affinity towards beta-adrenoceptors, with the [3H]batrachotoxinin A 20-alpha-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 (pKi values) with physicochemical 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 beta 1- and beta 2-adrenoceptor affinity with physicochemical parameters, leading to the conclusion that "cardioselective" beta-adrenoceptor ligands appear to have fewer membrane stabilizing properties.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Penbutolol	Beta-2 adrenergic receptor	Protein	Humans	Yes	Antagonist Partial agonist	Details