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Discovery of a natural peptide from black mamba venom, with anticholinergic properties

​In a collaborative study, a team from SIMoS (DMTS) identifies and characterizes a toxin isolated from black mamba venom, whose specific anticholinergic properties at the type 2 acetylcholine receptor, a regulator of arterial tone, position it as a potential drug candidate for the treatment of cardiovascular diseases.

Published on 21 November 2022

​The five muscarinic acetylcholine receptors (mAChRs) (M1-M5)* possess very important physiological and regulatory properties. While M1, M4 and M5 receptors are mainly expressed in neurons and glial cells of the central nervous system, in the heart, acetylcholine (ACh) binds to M2 and M3 subtypes and plays a crucial role in the control of cardiac excitability via the vagal nerve.
In order to better understand the contribution of each receptor subtype for a given function, scientists are looking for selective pharmacological tools, capable of binding only one receptor subtype. Snake venoms, and mamba venoms in particular, contain a proven diversity of toxins that interact with M1 and M4 mAChRs. These toxins (peptides of 65-66 residues) belong to the 3FTx (three-finger fold)** structural family and present different selectivity profiles and modes of action (antagonistic or allosteric interaction) on mAChRs.

In this study, researchers isolated, identified, synthesized and characterized for the first time a 3FTx toxin from black mamba venom, which binds only to the M2 receptor***, with no activity on the other 4 muscarinic receptor subtypes. This toxin, MT9, phylogenetically distinct from previously discovered muscarinic toxins, acts as a noncompetitive antagonist of acetylcholine in activation tests of isolated rat mesenteric arteries. These results were confirmed in human mammary arteries.

In conclusion, MT9, the first fully characterized natural toxin specific to the M2 endothelial receptor, should be able to position itself as a new drug candidate for the management of cardiovascular diseases.

Contact : Nicolas Gilles (

*The five muscarinic acetylcholine receptors (mAChRs) are members of the G protein-coupled receptor (GPCRs) superfamily. They contribute to multiple functions of the central and peripheral nervous systems, as well as to vegetative processes.
** The 3FTx or "three-finger" toxins, whose structure evokes three erect fingers, belong to the alpha-neurotoxin family, present in the venom of certain snakes.
*** Interestingly, to date, only one toxin purified from green mamba venom has been described as interacting with the M2 receptor but its characterization has remained incomplete.

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