NON-COMPETITIVE EFFECTS OF DISOPYRAMIDE AT THE NEUROMUSCULAR JUNCTION: EVIDENCE FOR ENDPLATE ION CHANNEL BLOCK
| Autor: | Ian G. Marshall, S.V.P. Jones |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
Male
Agonist medicine.medical_specialty Carbachol medicine.drug_class Neuromuscular Junction Tubocurarine In Vitro Techniques Motor Endplate Ion Channels Neuromuscular junction Membrane Potentials Internal medicine medicine Animals Magnesium Dose-Response Relationship Drug business.industry Rats Inbred Strains Neostigmine Rats Electrophysiology Anesthesiology and Pain Medicine medicine.anatomical_structure Endocrinology Mechanism of action Biophysics medicine.symptom Disopyramide business Chickens Acetylcholine Muscle Contraction medicine.drug |
| Zdroj: | British Journal of Anaesthesia. 59:776-783 |
| ISSN: | 0007-0912 |
| DOI: | 10.1093/bja/59.6.776 |
| Popis: | The effects of disopyramide were studied at the neuromuscular junction in an attempt to elucidate the mechanism of its blocking action at this site. Disopyramide 5 X 10(-5) - 10(-3) mol litre-1 produced a concentration-dependent reduction of twitch amplitude in the indirectly stimulated chick biventer cervicis preparation, but greater concentrations were required to reduce twitches elicited directly in the presence of erabutoxin-b 1 microgram ml-1. Equieffective twitch blocking doses of either disopyramide or tubocurarine greatly reduced agonist responses to acetylcholine and carbachol, but the reduction was less for magnesium-blocked twitches. Neostigmine antagonized tubocurarine-induced, but not disopyramide-induced, blockade of twitches. Concentration-response profiles to acetylcholine and carbachol were shifted to the right in a non-parallel fashion and the maximal response was depressed by disopyramide 5 X 10(-5) - 10(-4) mol litre-1. Intracellular recording studies carried out in the cut, voltage-clamped costo-cutaneous muscle of the garter snake showed that disopyramide 5 X 10(-5) - 5 X 10(-4) mol litre-1 produced a concentration- and voltage-dependent reduction of the amplitude of neurally evoked endplate-currents (EPC) and of the time constant of decay (tau) of EPC. We conclude that disopyramide possesses a non-competitive blocking action at the neuromuscular junction, which is not reversible by anticholinesterase agents. The voltage-dependent nature of the block suggests that it is mediated via blockade of the open form of the acetylcholine-activated receptor-ion channel complex. |
| Databáze: | OpenAIRE |
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