Conotoxins

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Conotoxins: essential data
Symptoms and Treatment, Toxicity, Chemistry, Site of Action, Sources, Properties, Terrorist Interest, IDC Codes
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Symptoms, Treatment, Decontamination
Syndrome Name	None
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. Burning pain; Swollen arm and pain; Local numbness, spreading rapidly to involve the entire body but without pain but with some cardiac and respiratory distress at the height of the poisoning; Progressive weakness, loss of coordination, drooping eyelids (ptosis), shallow breathing (a more recent case); Headache, nausea, stomach cramps, shortness of breath (also a recent case). All of those patients made full recoveries. Fatal cases included the following symptoms: Numbness without pain; Lips became stiff; Blurred vision; Paralysis: Coma.
Onset of Symptoms	Almost immediate upon injection.
Rapid diagnostic assay	None available
Antidote	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.

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Toxicity.
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.

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Chemical Properties
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. Click here for an overview of conotoxin structural classes. 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: A Greek letter prefix denoting the structural class (alpha, mu, omega, delta, kappa) A suffix including: one or two letters indicating the species (G = C. geographus, T = C. tulipa, P = C. purpurascens, Tx = C. textile, and so on.); a Roman numeral indicating the order of identification; a letter indicating a variant, such as GIIIA, GIIIB, and GIIIC.
Trivial Names	None.
Registry Number	Individual peptides have their own Registry numbers.
RTECS Number
Molecular Formula	Not applicable
Molecular weight	Not applicable
Solubility	Soluble in water and acidic acetonitrile.
pKa in water
Complete synthesis	Yes, but impractical on a weapons manufacturing scale.

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Site of Action

alpha	mu	omega
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.
delta	kappa	conantonkins
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.

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Source

Conotoxins are obtained from the toxin sacs of predatory snails of the species Conus found mainly in warm Pacific waters around Australia. The snails use their venom to immobilize and kill fish, shellfish, and marine worms. The toxins are small peptides that can be synthesized chemically in quantities sufficient for research use.

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Agent Properties

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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