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|Symptoms, Treatment, Decontamination|
|Symptoms||The conotoxins are paralytic poisons from Pacific cone snails that block
the transmission of a nerve impulse from the nerve to the muscle at the
neuromuscular junction. There are several classes of toxin in venom leading
to complex sets of symptoms. A collection of anecdotal reports of the
effects of being envenomated ("stung") by cone snails collected and published
in the Medical Journal of Australia in 1935 by H. Flecker included
the following symptoms in non-fatal cases.
All of those patients made full recoveries. Fatal cases included the following symptoms:
|Onset of Symptoms||Almost immediate upon injection.|
|Rapid diagnostic assay||None available|
|Supportive Care||Artificial respiration to support breathing and treatment of symptoms.|
|Inactivation||Inactivated by reactive disinfectants such as glutaraldehyde and formaldehyde. Thiol reagents such as BAL (British anti-Lewisite) may also be helpful in the event of aerosol use.|
| Individual conotoxins, even within the same class can vary greatly
in lethality towards mammals. Some of the tremor inducing omega conotoxins
are not lethal, whereas others of the same group are lethal at low levels.
However, the toxicicity in rats and mice is usually reported for the toxins
administered intracranially (into the brain). Some alpha conotoxins have
lethal doses as low as 25 micrograms/kg for mouse. This may be an overestimate
of toxicity because it is determined from the dose required to kill a
mouse in 20 minutes.
In addition, it has to be borne in mind that the toxicity of the complex mixture of peptides that is cone snail venom may be much greater than the sum of its parts because of the synergistic interaction between toxins acting on different aspects of neural function. Incidents of cone snails killing people are known to have occurred.
|Structure||Conotoxins are short peptides of 15-40 amino acids held in very tight
conformations by multiple disulfide bridges. These patterns of disulfide
bridge help to define a number of structural classes of conotoxin.
The image below is of conotoxin GIa prepared from structural information in the Brookhaven Protein Data Bank viewed using the ChIME plug-in for Netscape. The knotted conformation of conotoxins makes them difficult to represent by conventional chemical drawing representations. The disulfide bonds that give this knotted structure are colored yellow.
|Nomenclature||Conotoxins (or conopeptides) are named in a reasonably systemic manner:
|Registry Number||Individual peptides have their own Registry numbers.|
|Solubility||Soluble in water and acidic acetonitrile.|
|pKa in water|
|Complete synthesis||Yes, but impractical on a weapons manufacturing scale.|
|Nicotinic acetylcholine receptors. The effect is a paralysis similar to that seen with curare.||Sodium channels. This is also the target for saxitoxin and tetrodotoxin and the effects are similar.||Calcium channels associated with nerve impulse transmission at the neuromuscular junction.|
|Sodium channels. Unlike mu conotoxins, they slow the inactivation of the sodium channel.||Potassium channels. They are also known as shaker peptides because they block a potassium channel known as "Shaker" and as a result they induce tremors.||NMDA glutamate receptors. This blocks nerve impulses that use glutamic acid rather than acetylcholine as the neurotransmitter.|
These are small, very stable peptides that may be dispersable as aerosols for weapons use. Toxicity data on mammals are sparse, although a great deal is known about their sites of action, and the commonest assay appears to be based on direct injection into the brain, which does not give much of an indication of their toxicity in a weapons context. There do not seem to be any public data on their inhalation toxicity. They are poisonous by injection, which is functionally the same as envenomation by the snail.
Conotoxins are a very complex group of peptides with over two thousand variants known in the six structural classes identified. Individual members can be extremely specific for individual subtypes, of which there can be many, of the target molecule. The toxicity of the venom may come less from the considerable toxicity of a limited number of peptides than from the additive or synergistic effects of several toxins acting on different sites.
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