Selective neuromuscular blocking properties of alpha-conotoxins in vivo

Synthetic alpha-conotoxins GI and MI (based on the natural polypeptides isolated from Conus geographus and C. magus, respectively) were tested for effects on neuromuscular transmission and on the cardiovascular system in anaesthetised cats. Both produced neuromuscular blockade at doses of 20-80 micrograms/kg. Conotoxin GI was about 2.5 times more potent than MI. Both were rapidly reversed by the anticholinesterase neostigmine. At doses that abolished neuromuscular transmission, the alpha-conotoxins had no effects on arterial blood pressure, heart rate, or responses to vagal and preganglionic stimulation, indicating their specificity for nicotinic receptors at the neuromuscular junction.