NEUROTOXIC SNAKE ENVENOMING

The Ebers Papyrus (ca. 1550 BC) records neurotoxic symptoms reported by a patient bitten by a snake, probably the Egyptian cobra, 'I am as cold as water and then again as hot as fire. All my body sweats, and I tremble. My eyesight is not steady, and I cannot see for the sweat pours over my face.' Central American folklore says the bite of the tropical rattlesnake (Crotalus durissus) (Fig. 1) will break a person's neck wherever inflicted, thus reflecting the flaccid paralysis that may follow envenoming by this snake in some parts of its range. Early British accounts of snakebite in India mention inability to speak or swallow with foaming at the mouth, ptosis, fixed pupils, and other signs of cranial nerve palsies, as well as cyanosis from progressive respiratory failure. Numbness, cramps, difficulty in speaking and swallowing, and respiratory paralysis were described in early accounts of fatal coral snake poisoning in Florida. Nineteenth century research on chemistry of snake venoms established their protein nature and enzymatic activity. The first protein toxin from a snake venom to be isolated and characterized was crotoxin from venom of the Brazilian rattlesnake (C. durissus terrificus). It had neurotoxic activity and was subsequently shown to consist of a basic subunit with phospholipase A activity and a smaller acidic subunit. At about the same time, a neurotoxin with curare-like activity was isolated from Indian cobra venom. In the mid-1960s, by using ion exchange chromatography, postsynaptic neurotoxins were isolated from cobra and sea snake venoms. About 80 neurotoxins of this group have subsequently been isolated and sequenced. Synthesis of a peptide with the sequence and activity of one of the cobra neurotoxins has been accomplished.