Neuromuscular blocking activity of a new series of quaternary N-substituted choline esters.
1. The neuromuscular blocking activity of a new group of mono- and diquaternary N-substituted choline esters of several carboxylic acids has been evaluated in various whole animal preparations in the mouse, rat and cat.2. A basic non-depolarizing mechanism was present in all but one compound-a depolarizing agent, which was studied for comparison. There was evidence of facilitatory activity and nicotinic stimulation in the monoquaternary compounds. These effects were diminished in the diquaternary compounds.3. The presence of a bulky aromatic ring system on the nitrogen atom appeared to increase both neuromuscular blocking potency and facilitatory activity in the experimental animal. A similar relationship had previously been demonstrated in vitro in another study.4. The duration of action, although short in most compounds, did not correlate well with previously determined in vitro hydrolysis rates, possibly because of species differences.5. The general pharmacology of each compound appeared to depend considerably upon the structure of the choline moiety.
D000818:Animals; D002264:Carboxylic Acids; D002415:Cats; D002794:Choline / Q000494:pharmacology* / Q000633:toxicity; D004952:Esters / Q000494:pharmacology; D005703:Gallamine Triethiodide / Q000494:pharmacology; D005725:Ganglia, Autonomic / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology* / Q000633:toxicity; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013390:Succinylcholine / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology
D002264:Carboxylic Acids; D004952:Esters; D009467:Neuromuscular Depolarizing Agents; D003473:Neuromuscular Nondepolarizing Agents; D000644:Quaternary Ammonium Compounds; D009538:Nicotine; D013390:Succinylcholine; D002794:Choline; D005703:Gallamine Triethiodide; D014403:Tubocurarine