Potencies of neuromuscular blocking agents at the receptors of the atrial pacemaker and the motor endplate of the guinea pig.
Drug receptor dissociation constants (KB) were determined for four neuromuscular relaxants at the cardiac pacemaker as well as at the motor endplate. The ratios KB(atrium)/KB(lumbrical) were found to be high for d-tubocurarine and dimethyltubocurarine, 264 and 136, respectively. Thus, interaction at muscarinic sites would occur only with large doses of these drugs. In contrast, the ratios were low for pancuronium and gallamine, 5.3 and 2.4, respectively. Hence, the concentrations of these drugs needed for clinical neuromuscular blockade would occupy appreciable fractions of cardiac muscarinic receptors, and thus might produce vagal blockade and thereby produce the tachycardia seen clinically with these two agents.
D002628:Chemoreceptor Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D008297:Male; D009045:Motor Endplate / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects*; D010197:Pancuronium / Q000494:pharmacology; D013610:Tachycardia / Q000139:chemically induced; D014403:Tubocurarine / Q000031:analogs & derivatives / Q000494:pharmacology
D009466:Neuromuscular Blocking Agents; D010197:Pancuronium; D005703:Gallamine Triethiodide; D014403:Tubocurarine