Antipsychotics block muscarinic acetylcholine receptor-mediated cyclic GMP formation in cultured mouse neuroblastoma cells

Antipsychotic drugs (for example, phenothiazines, butyrophenones) have side effects similar to those of atropine, suggesting that they block the muscarinic acetylcholine receptor. Receptor-binding studies with radioactively-labelled ligands have been used to study the muscarinic acetylcholine receptor and to show that antipsychotic drugs vary in their potency at displacing the ligand from binding sites in rat brain homogenates. In all receptor binding studies it is essential to demonstrate that binding data in fact reflect a drug-receptor interaction in a pharmacological sense. These correlations are ideally determined using the same tissue for binding and for biological studies such as was done for certain polypeptide hormone receptors and for the β-adrenergic receptor. For the muscarinic acetylcholine receptor of nervous tissue, however, a direct correlation of binding data with pharmacological data has not been shown. Thus, there remains a question whether the displacement by antipsychotic drugs of a radioactively-labelled muscarinic receptor antagonist from brain homogenates reflects blockade by these drugs of this receptor. We report here that antipsychotic drugs block the muscarinic acetylcholine receptor in cultured nerve cells.