A STUDY IN VITRO OF NEW SHORT-ACTING NON-DEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS

Presently available short-acting, depolarizing myoneural blocking agents have significant side effects such as increased intraocular tension, cardiac arrhythmias desensitization of the postjunctional membrane, skeletal muscle injury and muscle pains. Non-depolarizing blocking drugs do not produce profound blocks of short duration. A program was evolved to synthesize compounds producing a non-depolarizing block at low concentrations with a brief action span requiring no antagonists. Several series of mono- and diquaternary esters of alkyl aminoethanols were prepared and studied in vitro. The rates of spontaneous hydrolysis and the hydrolysis catalyzed by acetylcholinesterase and plasmacholinesterase were measured. In addition, the anticholinesterase effects of these agents were evaluated. The myoneural blocking properties were studied with intracellular recordings in frog sciatic nerve-sartorius muscle preparations. Activity-structure relationships are reported. Several compounds warrant further study including investigations in vivo. © 1969.