Structure-activity relations of conotoxins at the neuromuscular junction.

The anticholinergic actions of synthetic conotoxin GI analogues and their structure-activity relationships were studied. Conotoxins competitively blocked the nicotinic acetylcholine receptors in neuromuscular junctions of preparations of rat sciatic nerve, M. gastrocnemius and frog abdominal muscles. They did not have a ganglion-blocking action, at least in the parasympathetic ganglion, or an anti-muscarinic action. The pA2 values of the synthetic conotoxin analogues indicated that the major factors determining the activity of conotoxin are the structural conformation of the peptide defined by two disulfide bridges, and the presence of a proline residue and C-terminal amide.