Interactions between suxamethonium and non-depolarizing neuromuscular blocking drugs.
In anaesthetized cats, we have confirmed that previously injected suxamethonium potentiates non-depolarizing neuromuscular blocking drugs whereas, when injected during the block, suxamethonium antagonizes the paralysis. We have attempted to explain these interactions by studying the effects of suxamethonium on extracellularly recorded nerve ending waveforms that correspond to the ionic currents in the mouse triangularis sterni isolated nerve-muscle preparation. The preparations were paralysed with mu-conotoxin (obtained from the cone snail), which is believed to act by selectively blocking sodium channels in muscle, and which therefore should not interfere with currents at the nerve endings. Suxamethonium, in concentrations of 0.5-300 mumol litre-1, produced a concentration-dependent increase in the amplitude of the waveform corresponding to the inward calcium current evoked by a nerve impulse. This effect did not occur in the presence of tubocurarine, suggesting that suxamethonium, which is a nicotinic agonist, may have been acting on a nicotinic receptor on the nerve endings that is coupled to the voltage-operated calcium channels. The inward calcium current is believed to be responsible for neurotransmitter (acetylcholine) release. It is concluded, therefore, that its enhancement by suxamethonium contributes to the ability of this drug to reverse non-depolarizing block. Suxamethonium also exerted complex effects on the waveform corresponding to the outward flowing calcium-activating potassium current at the nerve endings, but no effect was observed in this isolated nerve-muscle preparation that could obviously explain the ability of suxamethonium to potentiate subsequently injected non-depolarizing blocking drugs.
Braga
M F
MF
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow.
Rowan
E G
EG
Harvey
A L
AL
Bowman
W C
WC
D015761:4-Aminopyridine / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000077770:Amifampridine; D000818:Animals; D002415:Cats; D004347:Drug Interactions; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009119:Muscle Contraction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013390:Succinylcholine / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013997:Time Factors; D014403:Tubocurarine / Q000037:antagonists & inhibitors; D014673:Vecuronium Bromide / Q000494:pharmacology
D003473:Neuromuscular Nondepolarizing Agents; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D014673:Vecuronium Bromide; D015761:4-Aminopyridine; D013390:Succinylcholine; D000077770:Amifampridine; D014403:Tubocurarine