The pharmacological action of MT-7

The mamba toxin MT-7 is the most selective ligand currently available for the muscarinic M₁ receptor subtype. The toxin binds stably to the receptor and blocks the agonist-induced activation non-competitively. Although its mode of action on M₁ receptors is not yet fully understood, some of the toxin properties support an allosteric mechanism. Thus, the toxin fails to elicit a complete inhibition of the binding of either the muscarinic antagonist [³H]N-methyl-scopolamine ([³H]NMS) or the agonist [³H]acetylcholine ([³H]ACh). When added to ligand-occupied M₁ receptors, the toxin slows the dissociation rate of [³H]NMS and increases that of [³H]ACh. Site-directed mutagenesis studies have provided important information about the toxin amino acid residues which are critical for the stable binding to the receptor and for the allosteric modulation of antagonist dissociation. In vivo studies have shown that the intracerebral injection of MT-7 causes a long-lasting blockade of M₁ receptor, thus providing a tool for the characterization of the functional role of this receptor subtype in discrete brain areas.