NEUROMUSCULAR BLOCKING-AGENTS - SOME APPROACHES TO SHORT-ACTING COMPOUNDS

A series of amidic and N-methylamidic methyl and trideuteromethyl quaternary analogues of atracurium have been prepared. All were less potent and longer acting neuromuscular blocking agents than atracurium, and all showed appreciable vagal blockade at neuromuscular blocking doses. Replacement of NCH3 by NCD3 failed to affect potency. Fluorosubstitution in the central chain did not reduce duration of action. Attachment of acyloxy substituents to the interquaternary chain of atracurium and related compounds adjacent to their ester groups shortened the duration of action significantly. Diformyloxy substitution was the most effective in reducing duration without adversely affecting other properties apart from potency, which was significantly less than that of atracurium.