Antagonism of Benzodiazepine Binding in Brain by Antilirium, Benzyl Alcohol, and Physostigmine

Abstract: Antilirium®, which contains eserine (physostigmine) and benzyl alcohol, is effective in reversing diazepam-induced sleep in man and is capable in vitro of inhibiting the binding of labeled benzodiazepine to both rat and human brain homogenates in a dose-dependent manner. We have examined the constituents of Antilirium and report that both benzyl alcohol and eserine inhibit ³HI-diazepam binding to rat brain in a dose-dependent manner. A major portion of the inhibition of binding found with Antilirium is accounted for by benzyl alcohol. Scatchard analysis of inhibition of benzodiazepine binding by benzyl alcohol reveals loss of binding sites and change in equilibrium dissociation constant. Methanol, ethanol, and butanol did not inhibit benzodiazepine binding. The inhibition by benzyl alcohol may be specific since there was no inhibition of labeled ligand binding to the γ-aminobutyric acid, opiate, muscarinic acetylcholine, or β-adrenergic receptors. The other constituent, eserine, is a competitive inhibitor. While eserine is a more potent inhibitor at the benzodiazepine receptor than is benzyl alcohol, it is also much less specific. Eserine inhibited binding of labeled ligand to the γ-aminobutyric acid, opiate, and muscarinic acetylcholine receptors. The inhibition of benzodiazepine binding to brain in vitro by Antilirium and its constituents, eserine and benzyl alcohol, may be the explanation, at least in part, for the reversal by Antilirium of diazepam-induced narcosis in viva, without postulating a cholinergic mechanism for the in vivo effect.