Calciseptine (CaS) is a natural neurotoxin isolated from the black mamba Dendroaspis p. polylepis venom.

[1] The black mamba (Dendroaspis polylepis) is generally considered to be one of the deadliest snakes on the planet,[2][3] and is responsible for many fatalities throughout its sub-Saharan Africa range.

The three steps were: 1) gel filtration, 2) ion exchange on TSK SP 5PW and 3) reverse-phase chromatography on RP18.

[7] The activities of these toxins - although they are members of the same family - are actually quite diverse and can range from the blocking of acetylcholine receptors to the changing of membrane permeability.

Although the toxic peptides are generally small (about 60 amino acids), their size is sufficient to prevent them from crossing epithelial layers like the blood–brain barrier.

[11] In general, toxic peptides of 10-40 amino acids have been found to have a relatively poor bioavailability due to their size and hydrophilicity.

It has been found that digestion of snake toxic peptides by proteases does occur in the prey tissues, but due to the relative stability of the toxins, the speed with which the toxins act and the amount of venom injected, this is not enough to protect against the consequences of a snake bite.

The reason this structure is so much conserved is probably its stability: the cysteine bridges create a stable core, which possibly slows the breakdown of the protein by proteases.

[10] Calciseptine has been shown to block L-type calcium channels, thus inhibiting smooth muscle contraction and cardiac function.

N-type Ca2+ channels are found in neuronal cells, and play an important role in the coupling of nerve excitation and neurotransmitter secretion.

[1][7][13] Calciseptine resembles the abovementioned 1,4-dihydropyridines in its biological action, as it has the same ability to bind and block the L-type calcium channels in smooth and cardiac muscle.

Multiple sequence alignment studies yielded 12 amino acid residues that were unique to the toxins with channel-blocking activities.

A model has been proposed in which the amino acids 45 to 48, MWPY, of the FS2 toxin are considered to bind the calcium channels.

A short polypeptide of eight amino acid residues, containing this sequence, was indeed found to block the L-type calcium channels, though with a lesser activity.

[7][15] Typical symptoms after being bitten by a black mamba include the rapid onset of dizziness, drowsiness and coughing and having difficulties breathing.

In the most severe case, if untreated, the bite of the black mamba can lead to death by suffocation, resulting from the paralysis of respiratory muscles.

[16] All these symptoms are due to a combination of all the toxic peptides the crude venom of the black mamba contains.

The symptoms are related to calciseptine because it also works as a smooth muscle relaxant,[1] thus explaining the early onset of having difficulties breathing, limb paralysis and even death by suffocation.

The venom is also administered with an adjuvant, like aluminium hydroxide or sodium alginate, to stimulate the immunological response.

These will bind components – the variability of peptides – of the venom, which prevent further activity of the molecule and are ultimately removed by the immune system of the body.

However, the LD50 values for mice have been determined and can be found in the table below:[20] The black mamba can inject 100–120 mg venom in one bite.

Calciseptine relaxes precontracted rat (thoracic) aorta and decreases blood pressure drastically.

[1] The inhibitory effect of calciseptine results in a decreased or total disappearance of electric activity in these cells.

[23] In adult frog skeletal muscle fibers calciseptine also causes an increased Ca2+ current.

[23] Research on rats and guinea pigs revealed that synthetic calciseptine and FS2 as well, have the same effect as their natural counterparts.