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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Munday, I. T. Lees, G. Edwards, M. D. Jones, R. M. |
| Description | Author Affiliation: Lees G ( Department of Anaesthetics, Imperial College of Medicine, (St Mary's Hospital Medical School), London.) |
| Abstract | 1. The in vitro potency and mode of action of the novel, rapid-onset steroidal relaxant ANQ9040 were characterized in the rat isolated phrenic nerve hemidiaphragm. 2. At 32 degrees C, ANQ9040 antagonized neurally evoked contractures with EC50s of 21.5 microM for unitary twitches; 14.4 microM for 2 Hz 'trains of four'; and 7.5 microM for 50 Hz (2 s) tetanic stimulus trains. 3. (+)-Tubocurarine was 22-24 times more potent than ANQ9040 in comparative organ bath experiments. 4. Intracellular recording from endplates revealed that ANQ9040 (0.53-10.0 microM) dose-dependently and reversibly decreased the amplitude of miniature-endplate potentials (IC50 of circa 0.95 microM) without changing transmembrane potential. 5. Surmountable antagonism of subthreshold responses to exogenous (ionophoretic) acetylcholine provided evidence for a non-depolarizing and competitive blockade of post-junctional nicotinic receptors. 6. Sucrose gap recordings of phrenic nerve action potentials revealed that, at concentrations up to 32 microM, ANQ9040 produced no tonic or frequency-dependent antagonism of axonic Na+ channels. 7. We conclude that ANQ9040 is a relatively low-affinity, non-depolarizing, nicotinic antagonist. The in vitro results are discussed in relation to factors impinging on relaxant kinetics and current models for frequency-dependent fade. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 2 |
| Volume Number | 113 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1994-10-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Androstanes Pharmacology Azasteroids Neuromuscular Nondepolarizing Agents Action Potentials Drug Effects Animals Axons Metabolism Diaphragm Electric Stimulation Electrophysiology In Vitro Techniques Mannitol Muscle Contraction Phrenic Nerve Cytology Rats, Sprague-Dawley Sodium Channels Tubocurarine |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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