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 0007-0912Full text not available in this repository. (Request a copy from the Strathclyde author)
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.
|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:||27 Apr 2016 14:18|