Muscarinic toxins from the green mamba

Muscarinic acetylcholine receptors are involved in many important physiological processes. Discovery of different subtypes of muscarinic receptors that are responsible for modulating specific physiological events was a key development in muscarinic receptor research. However, the lack of highly selective muscarinic agonists and antagonists has made the classification of a muscarinic receptor subtype responsible for the mediation or modulation of a particular response very difficult. Toxins have previously proved to be highly useful pharmacological tools, due to their high potency and selectivity. This review looks at a new class of muscarinic ligand isolated from the venom of the Eastern green mamba (Dendroaspis angusticeps). Just over a decade ago, it was found that two toxins from the green mamba venom appeared to distinguish between different muscarinic receptor subtypes. Since then, at least 10 more muscarinic toxins (MTs) have been isolated from mamba venom. In recent years, some of the MTs have been used as pharmacological tools; for example, to determine the muscarinic receptor subtype involved in inhibition of adenylyl cyclase in rat striatum. This review looks at the progress that has been made over the past 10 years in the area of MT research and examines whether or not these new peptides are a new way forward in the field of muscarinic receptor research.