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Prejunctional action of neostigmine on mouse neuromuscular preparations

Braga, M.F.M. and Rowan, E.G. and Harvey, Alan L. and Bowman, W.C. (1993) Prejunctional action of neostigmine on mouse neuromuscular preparations. British Journal of Anaesthesia, 70 (4). pp. 405-410. ISSN 0007-0912

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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 mumol litre-1 continued to produce some antagonism of tubocurarine-induced block after cholinesterase had been inactivated completely by diisopropyl fluorophosphate 22 mumol litre-1. In the mouse triangularis sterni preparation, neostigmine 0.1-1 mumol 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 mumol 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. Physostigmine and pyridostigmine did not possess this additional action.

Item type: Article
ID code: 18521
Keywords: nicotinic acetylcholine receptor, motor nerve terminals, muscle, anticholinesterases, pyridostigmine, Pharmacy and materia medica, Anesthesiology and Pain Medicine
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Depositing user: Dr EG Rowan
Date Deposited: 17 Nov 2010 14:32
Last modified: 21 May 2015 11:28

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