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Muscarinic Toxin 2 One of the two original green mamba muscarinic toxins; it binds M1 and M4 near-irreversibly and acts as a slow muscarinic agonist, but it is markedly less selective than its early reputation suggested.
- the first peptide ligand ever found for muscarinic receptors
- produces M1 activation that persists through washout
- improves memory consolidation in rats after intrahippocampal injection
- binds M4 as well as M1, which suits experiments that want both
- not M1-selective; activates M3 and M5 at higher concentrations
- binds alpha-1 adrenoceptors
- the activation does not wash out, so a preparation is single use
- no human data of any kind
- the abbreviation collides with melanotan II in most search results
Overview
Historically important and now mostly a cautionary tale. Described as an M1-selective agonist for over a decade on the strength of binding assays, it turned out under functional testing to activate M3 and M5 as well and to bind alpha-1 adrenoceptors. Anyone still calling it selective is quoting the 1990s literature rather than the current picture; MT7 has taken over the M1 work.
- MT2 was treated as an M1-selective ligand for more than a decade on the strength of radioligand binding; when it was finally tested functionally in transfected cells it turned out to activate M3 and M5 as well.
Mechanism
MT2 binds receptors in two steps, a fast low-affinity encounter followed by a slow isomerisation into a much more stable complex, which is what gives it high apparent potency despite a weak initial interaction [4]. In radioligand work it inhibits N-methylscopolamine binding at cloned M1 and M4 receptors essentially irreversibly, binds M5 with lower affinity, and reversibly displaces prazosin from alpha-1 adrenoceptors at roughly 20-fold lower affinity, so it is not a -only [3].
Functionally it behaves as an rather than a blocker: in CHO cells it raises cytosolic calcium through m1 above 100 nM, through m3 between 25 and 800 nM and through m5 between 800 and 1600 nM, a much wider profile than the binding assays had implied [2]. The activation appears to happen at a site distinct from the pocket, since the responses are not reversed by washing and are not prevented by conventional antagonists [3].
receptor fingerprint
M1 (CHRM1)Agonist, effectively irreversible
M4 (CHRM4)High-affinity binder
M3 (CHRM3)Weak agonist
M5 (CHRM5)Weak agonist
Alpha-1 adrenoceptorReversible binder
Safetyrisks and cautions, not medical advice
There is no human exposure to MT2 and no toxicology on the purified protein; everything known comes from rodent brain injections and cell assays. Injected into the dorsal hippocampus of rats immediately after training, MT2 improved memory consolidation on an inhibitory avoidance task, the opposite direction from MT3 in the same experiment [5]. Because the M1 activation does not wash out, a tissue or an animal exposed to it stays exposed, which is a practical problem in an experiment rather than a clinical risk [3]. Its activity at M3 and M5 and its affinity for alpha-1 adrenoceptors mean any physiological effect attributed to M1 needs controls before it can be believed [2].
History
MT2 was one of the first two muscarinic toxins ever described, isolated from green mamba venom at Uppsala in 1988 alongside MT1, at a point when no peptide was known to act on muscarinic receptors at all. Early competition work against pirenzepine suggested it was M1-preferring, and groups in South America used it through the 1990s as a muscarinic agonist in memory consolidation experiments. That selectivity claim did not survive functional testing; by 2002 and 2003 the same toxin was shown to activate M3 and M5 in transfected cells and to bind alpha-1 adrenoceptors in brain and vas deferens. It has since been displaced by MT7 for M1 work and survives mainly as the compound that established that snake venom contains muscarinic ligands at all.
Reputation
MT2 sits in an awkward place: genuinely important historically, and now cited as often for what it got wrong as for what it does. It is still sold and still used, but a modern reader should treat any description of it as a selective M1 agonist as out of date. Outside the muscarinic toxin literature almost nobody has heard of it, and its abbreviation is far better known as shorthand for melanotan II.
Subjective profileweighing the evidence above
Historically important and now mostly a cautionary tale. Described as an M1-selective agonist for over a decade on the strength of binding assays, it turned out under functional testing to activate M3 and M5 as well and to bind alpha-1 adrenoceptors. Anyone still calling it selective is quoting the 1990s literature rather than the current picture; MT7 has taken over the M1 work.
Resources
This entry is here for reference.
Research
- 1988first citedToxins from the venom of the green mamba Dendroaspis angusticeps that inhibit the binding of qu…
- 2011most recentMuscarinic toxins
- 1.Toxins from the venom of the green mamba Dendroaspis angusticeps that inhibit the binding of quinuclidinyl benzilate to muscarinic acetylcholine receptors
- 2.Effects of muscarinic toxins MT2 and MT7, from green mamba venom, on m1, m3 and m5 muscarinic receptors expressed in Chinese Hamster Ovary cells
- 3.Effects of muscarinic toxins MT1 and MT2 from green mamba on different muscarinic cholinoceptors
- 4.Two-step binding of green mamba toxin to muscarinic acetylcholine receptor
- 5.Role of hippocampal M1 and M4 muscarinic receptor subtypes in memory consolidation in the rat
- 6.Muscarinic toxins from the venom of Dendroaspis snakes with agonist-like actions
- 7.Anti-muscarinic toxins from Dendroaspis angusticeps
- 8.Muscarinic toxins: novel pharmacological tools for the muscarinic cholinergic system
- 9.Muscarinic toxins
9 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is MT2 the same as melanotan II?
No, and the collision causes real confusion. Melanotan II is a synthetic melanocortin peptide taken for tanning; MT2 here is muscarinic toxin 2, a 7 kDa protein from green mamba venom that acts on muscarinic acetylcholine receptors. They share nothing but an abbreviation.
Is MT2 an agonist or an antagonist?
An agonist, though it took functional work to establish that. In binding assays it looks like a blocker because it displaces the radioligand; in cells it raises intracellular calcium through M1, M3 and M5, which is agonist behaviour.
Why is it called a slow agonist?
Because the association happens in two stages. The first contact is fast and weak, and the second is a slow rearrangement into a complex that barely comes apart. The result is a response that takes a long time to develop and then does not reverse.
Should MT2 still be used to probe M1?
Not on its own. MT7 is more selective by orders of magnitude and has no adrenoceptor activity, so for anything that needs a clean M1 attribution it is the better tool. MT2 remains useful where a persistent, non-washable activation of M1 is what the experiment actually calls for.
Adverse effects
- not M1-selective; activates M3 and M5 at higher concentrations
- binds alpha-1 adrenoceptors
- the activation does not wash out, so a preparation is single use
- no human data of any kind
- the abbreviation collides with melanotan II in most search results