Neuromuscular Blocking Agents--VI. Linear Tetra, Penta-, and Hexa-onium Compounds

Observations Upon Roles of Ether Oxygen, Alkyl Group Size, Number of Onium Centres and Interonium Distance Upon Neuromuscular Block in Bis‐ and Polyonium Compounds

“…Systems of classifying neuromuscular blocking agents which depend upon an attempted correlation of the type of block produced with molecular structural features have proved, in the main, to be unsatisfactory. Thus the stereochemical classification of neuromuscular blocking agents into pachycurares and leptocurares (Bovet, 1951) fails, for example, to account for the depolarizing activity of nicotine, the lack of depolarization by tridecamethonium, tridecamethylene-bis(trimethylammonium), in the chicken (Zaimis, 1952) and by many other linear polyonium muscle relaxants (see Edwards, Stenlake, Lewis & Stothers, 1961, for references). The equidistance concept of neuromuscular blocking activity by bisand tris-onium compounds (for example, Barlow & Ing, 1948;Pfeiffer, 1948;Paton & Zaimis, 1949;Kimura & Unna, 1950) over-emphasized molecular linearity and a onedimensional spatial arrangement and failed to consider the conformational isomerism possible about carbon bonds in non-rigid molecules.…”