title: Potentiation between neostigmine and 3,4-diaminopyridine in antagonizing the neuromuscular block induced by D-tubocurarine.
abstract: The antagonisms to the d-tubocurarine-induced neuromuscular blockade by neostigmine and 3,4-diaminopyridine (DAP) were studied quantitatively in the isolated phrenic nerve-diaphragm preparation of mice in vitro and in lethality of mice in vivo by assaying concentrations of d-tubocurarine needed to produce 70% block of indirect muscle contraction and LD50, respectively. The "antagonist efficacies", defined as the ratio of d-tubocurarine concentration (dose) after pretreatment with antagonistic agents over that of control, were 1.87, 2.24 and 14.7, respectively, for neostigmine, DAP and both agents combined when the stimulus pulses were at 0.1 Hz. Under 50 Hz train stimulation, the antagonist efficacies were lower, being 1.85, 1.64 and 5.33, respectively. For the lethality to d-tubocurarine, the values were still lower, being only 1.21, 1.33 and 1.84, respectively. The synergism between neostigmine and DAP, as evident from the marked increase of antagonist efficacy in vitro, is more than expected from the possible interaction of the major pharmacological actions of these two agents.
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives*; D000077770:Amifampridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D005260:Female; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009388:Neostigmine / Q000494:pharmacology*; D009407:Nerve Block / Q000009:adverse effects; D009435:Synaptic Transmission / Q000187:drug effects; D014403:Tubocurarine / Q000037:antagonists & inhibitors* / Q000633:toxicity
chemical_list: D000631:Aminopyridines; D009388:Neostigmine; D015761:4-Aminopyridine; D000077770:Amifampridine; D014403:Tubocurarine