Structure:action relationships among some desacetoxy analogues of pancuronium and vecuronium in the anesthetized cat.
The hypothesis that the neuromuscular blocking potency of pancuronium and vecuronium depends on the two acetylcholine moieties present at positions 3 and 17 was tested in cats by examining the neuromuscular profile of several desacetoxy analogues. Blockade of sciatic nerve-induced contraction of the tibialis and soleus muscles, as well as the effects on vagal-induced bradycardia and on sympathetically induced contractions of the nictitating membrane, were studied. The bis-desacetoxy analogue of pancuronium (ORG 7931) was one-fifth as potent as the parent compound as a neuromuscular blocking drug and as a vagolytic agent, but the neuromuscular block was faster in onset and shorter in duration than that produced by pancuronium. The desacetoxy analogues of vecuronium (ORG 8730 and ORG 8764) also were less potent neuromuscular blocking drugs, and, in addition, produced more vagal block than did vecuronium itself. The neuromuscular block produced by these desacetoxy analogues was of more rapid onset and shorter duration than that produced by vecuronium. The results thus showed that the greater neuromuscular blocking potency of pancuronium and vecuronium is lost after removal of one or both of the acetylcholine moieties. An analysis of the relationship between neuromuscular blocking dose and duration of action revealed that it was reciprocal, and it is suggested that a nondepolarizing equivalent of suxamethonium, when discovered, may necessarily be a drug of relatively low potency.
D000818:Animals; D002415:Cats; D005260:Female; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D010197:Pancuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014673:Vecuronium Bromide / Q000031:analogs & derivatives* / Q000494:pharmacology
D009466:Neuromuscular Blocking Agents; C056450:(dideacetoxy)vecuronium; C056447:(dideacetoxy)pancuronium; D014673:Vecuronium Bromide; C056449:3-(deacetoxy)vecuronium; C056448:3-(deacetoxy)pancuronium; D010197:Pancuronium