PREJUNCTIONAL ACTION OF NEOSTIGMINE ON MOUSE NEUROMUSCULAR PREPARATIONS

• Published in: British Journal of Anaesthesia 1993-04, Vol.70 (4), p.405-410
• Main Authors: BRAGA, M.F.M., ROWAN, E.G., HARVEY, A.L., BOWMAN, W.C.
• Format: Article
• Language: English
• Subjects: Anesthetics. Neuromuscular blocking agents; Animals; Antagonists: neostigmine; Biological and medical sciences; Cholinesterase Inhibitors - pharmacology; Diaphragm - innervation; Dose-Response Relationship, Drug; In Vitro Techniques; Male; Medical sciences; Membrane Potentials - drug effects; Mice; Mice, Inbred BALB C; Neostigmine - pharmacology; Neuromuscular function: acetyl-choline release; Neuromuscular Junction - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Phrenic Nerve; Potassium Channels - drug effects; Tubocurarine - antagonists & inhibitors
• ISSN: 0007-0912; 1471-6771
• DOI: 10.1093/bja/70.4.405

We have studied the effects of neostigmine on the mouse diaphragm and triangularis sterni isolated nerve-muscle preparations. Mechanical responses of the muscle, end-plate potentials and miniature end-plate potentials, and extracellularly recorded nerve ending currents were recorded. In the mouse diaphragm nerve-muscle preparations, neostigmine 1 μmol litre−1 continued to produce some antagonism of tubocurarine-induced block after cholin-esterase had been inactivated completely by di-isopropyl fluorophosphate 22 μmol litre −1. In the mouse triangularis sterni preparation, neostigmine 0.1–1 μmol litre−1 increased the quantal content of the end-plate potential in a concentration-dependent manner. This effect appeared to be sufficient to account for the cholinesterase-independent antagonistic action to tubocurarine under the conditions of the experiments. Neostigmine 1–100 μmol litre−1 depressed the amplitude of the K+ currents of the perineural waveforms in a concentration-dependent manner, and this may account for its ability to increase the quantal content of the end-plate potential. Although inhibition of acetyl-cholinesterase is the main mechanism of action of neostigmine, the drug also exerts an additional direct action on motor nerve endings to block the delayed rectifier K+ channels and enhance transmitter release. This effect occurred at clinically relevant concentrations of neostigmine. Physo-stigmine and pyridostigmine did not possess this additional action. (Br. J. Anaesth. 1993; 70: 405–410)