3,4-Diaminopyridine reverses respiratory paralysis induced by a presynaptically active snake venom and its major neurotoxin

Abstract

Presynaptically active snake venom neurotoxins induce a potentially fatal neuromuscular blockade which cannot be reliably overcome by current therapy. The drug 3,4-diaminopyridine (DAP) is effective in other presynaptic paralytic conditions and was therefore tried in anaesthetized rabbits with respiratory paralysis induced by krait ( Bungarus fasciatus) venom. A strain gauge pneumograph measured rabbit chest circumference during the respiratory cycle to document objectively effects of toxins and treatments. DAP counteracted the effects of both whole krait venom and its purified presynaptically active component, β-bungarotoxin. Respiratory excursions increased within 4–8 min after DAP injection in animals paralysed with β-bungarotoxin and 4–10 min after the injection of DAP in animals paralysed with 1 mg/kg whole krait venom. The onset of complete respiratory paralysis after a lethal dose of whole krait venom (2 mg/kg) was delayed significantly by DAP. This is the first indication that presynaptic venom paralysis can be reversed and suggests that DAP merits further evaluation as treatment for this condition.