data + articles · 11 listed
newest 2020spec sheet7 rows
Muscarinic Toxin 7 A 65 residue three-finger protein from green mamba venom that blocks the M1 muscarinic receptor from an allosteric site; it is the most subtype-selective muscarinic ligand anyone has found.
- proves an effect is M1-mediated
- blocks M1 with no measurable action at M2 to M5
- no detectable adrenoceptor binding, unlike its relatives
- the block survives washout, so timing is easy to control
- a working scaffold for engineering new receptor-selective proteins
- no human data of any kind
- irreversible on the experimental timescale, so a preparation cannot be reused
- a 7 kDa protein, so in vivo work needs direct injection into tissue
- expensive and supplied in microgram amounts
- displaced by low molecular weight polyethylene glycols, which caused real trouble during crystallisation
Overview
The reagent that settles the argument. If an effect survives MT7, the M1 attribution is usually accepted, and no small molecule comes close to that standard of proof. The cost is that it is a protein, so it has to be delivered to the tissue directly, and once it is on the receptor it does not come off.
- Membranes treated with MT7 and then washed by centrifugation and resuspension had still not recovered normal antagonist binding after eight hours at 30 degrees C.
- Structure-guided mutation of MT7's three finger loops re-pointed it from M1 to M2, which was the first time a snake three-finger toxin had its receptor target deliberately switched.
Mechanism
MT7 binds the extracellular vestibule of the M1 receptor rather than the pocket, which makes it an rather than a competitive one [2]. The 2.55 angstrom crystal structure of the M1 receptor with MT7 bound shows the toxin's second finger loop plugging the entrance to the orthosteric site while contacts with extracellular loop 2 and the top of transmembrane helix 7 hold the receptor in its inactive shape; those contact residues are precisely the ones not conserved across M1 to M5, which is where the selectivity comes from [1].
Functionally it is a negative modulator of signalling and a positive allosteric modulator of binding: it abolishes -stimulated GTPgammaS binding and inositol phosphate accumulation at M1 while leaving M2, M3 and M4 untouched, and it slows N-methylscopolamine dissociation about fivefold [2]. Only a handful of receptor residues carry the preference; substituting two M1 glutamates into the equivalent positions of M3 is enough to convert M3 into an MT7 binder [4]. Synthetic MT7 is at least 20,000 times more potent at M1 than at any other subtype and binds quasi-irreversibly; mutating the single arginine at position 34 restores reversibility [3].
receptor fingerprint
M1 (CHRM1)Allosteric antagonist
M2 (CHRM2)No measurable activity
M3 (CHRM3)No measurable activity
M4 (CHRM4)No measurable activity
M5 (CHRM5)No measurable activity
Alpha adrenoceptorsNo measurable activity
Safetyrisks and cautions, not medical advice
MT7 has never been given to a person. It is a laboratory reagent, and the green mamba venom it is purified from is medically dangerous for reasons that have nothing to do with this component. Its own pharmacology describes what an exposure would do: a complete and durable shutdown of M1 signalling with the M2 to M5 arms of cholinergic transmission left running.
The block does not wash off; membranes pretreated with MT7 and then washed do not recover normal antagonist binding for at least eight hours at 30 degrees C, so the effect outlasts the exposure by a wide margin [2]. Unlike several of its relatives it shows no detectable binding to adrenoceptors, so the usual off-target confound for this toxin family does not apply to it [8]. Toxicity, immunogenicity and systemic distribution of purified MT7 have not been studied in humans, so nothing can be said about what a whole-body exposure would look like.
History
Green mamba venom was shown to contain antimuscarinic proteins in 1988 by Adem and colleagues in Uppsala, which is where the MT1 to MT7 numbering begins. Potter's laboratory in Miami independently purified the principal anti-M1 component in 1993 and named it m1-toxin for what it did rather than where it sat in a fraction order; later work resolved that activity into a family of near-identical isotoxins, of which m1-toxin1 has the same sequence as the toxin the European groups were calling MT7.
Total chemical synthesis in 2003 made the toxin available without the snake and showed that a single arginine at position 34 is what makes the binding stick. In 2020 a Stanford group solved the crystal structure of the M1 receptor with MT7 bound and then used it to re-point the toxin at M2, the first demonstration that the three-finger fold can be deliberately reprogrammed as a scaffold for receptor-selective proteins.
Reputation
Among muscarinic pharmacologists MT7 is the gold standard for M1 selectivity, and a result that survives it is generally taken as M1-mediated. It is sold in microgram quantities by specialist peptide suppliers and is essentially unknown outside receptor pharmacology and structural biology. Its standing rose again in 2020, when the structure turned it from a useful blocker into a design template.
Subjective profileweighing the evidence above
The reagent that settles the argument. If an effect survives MT7, the M1 attribution is usually accepted, and no small molecule comes close to that standard of proof. The cost is that it is a protein, so it has to be delivered to the tissue directly, and once it is on the receptor it does not come off.
Resources
This entry is here for reference.
Research
- 1993first citedPurification and properties of m1-toxin, a specific antagonist of m1 muscarinic receptors
- 2020most recentStructure and selectivity engineering of the M1 muscarinic receptor toxin complex
- 1.Structure and selectivity engineering of the M1 muscarinic receptor toxin complex
- 2.Inhibition of acetylcholine muscarinic M(1) receptor function by the M(1)-selective ligand muscarinic toxin 7 (MT-7)
- 3.Chemical synthesis of MT1 and MT7 muscarinic toxins: critical role of Arg-34 in their interaction with M1 muscarinic receptor
- 4.Muscarinic toxin 7 selectivity is dictated by extracellular receptor loops
- 5.Effects of muscarinic toxins MT2 and MT7, from green mamba venom, on m1, m3 and m5 muscarinic receptors expressed in Chinese Hamster Ovary cells
- 6.Action of the muscarinic toxin MT7 on agonist-bound muscarinic M1 receptors
- 7.Different interactions between MT7 toxin and the human muscarinic M1 receptor in its free and N-methylscopolamine-occupied states
- 8.Adrenoceptor activity of muscarinic toxins identified from mamba venoms
- 9.m1-toxin isotoxins from the green mamba (Dendroaspis angusticeps) that selectively block m1 muscarinic receptors
- 10.Purification and properties of m1-toxin, a specific antagonist of m1 muscarinic receptors
- 11.Muscarinic toxins
11 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is MT7 the same thing as m1-toxin?
Yes. Two laboratories found the same protein and named it by different conventions; the Swedish numbering gave MT7, and Potter's group in Miami named it for its target as m1-toxin, later refined to m1-toxin1 once the near-identical isotoxins were separated.
Can I take MT7?
No. There is no human formulation, no human dose and no human safety data. It is a venom protein sold to laboratories as a receptor probe, it would not survive the gut, and it does not reach the brain from the bloodstream.
Why call it irreversible when nothing really is?
Because on any timescale an experiment runs, it behaves that way. Washed membranes still had not recovered normal antagonist binding after eight hours at 30 degrees C, so the dissociation constant cannot even be measured by the usual methods.
Does MT7 block acetylcholine directly?
Not at the acetylcholine site. It sits above it, in the extracellular vestibule, with one of its finger loops covering the entrance. That is why it slows the exit of an antagonist already bound underneath it while still shutting down agonist signalling.
What makes it so much more selective than a small molecule?
It reads the extracellular loops rather than the binding pocket. The acetylcholine pocket is nearly identical across M1 to M5, but the loops above it are not, and a protein large enough to touch several of them at once can tell the subtypes apart.
Adverse effects
- no human data of any kind
- irreversible on the experimental timescale, so a preparation cannot be reused
- a 7 kDa protein, so in vivo work needs direct injection into tissue
- expensive and supplied in microgram amounts
- displaced by low molecular weight polyethylene glycols, which caused real trouble during crystallisation