Mechanism of neuromuscular blockade induced by phenthonium, a quaternary derivative of (-)-hyoscyamine, in skeletal muscles

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dc.contributor.authorSouccar, Caden [UNIFESP]
dc.contributor.authorLima-Landman, MTR
dc.contributor.authorBallejo, G.
dc.contributor.authorLapa, Antonio José [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T12:30:36Z
dc.date.available2016-01-24T12:30:36Z
dc.date.issued1998-07-01
dc.description.abstract1 the mechanisms underlying the postjunctional blockade induced by phenthonium [N-(4-phenyl) phenacyl 1-hyoscyamine] were investigated in mammalian and amphibian muscles. This muscarinic antagonist was previously shown to enhance specifically the spontaneous acetylcholine (ACh) release at concentrations that blocked neuromuscular transmission.2 in both rat diaphragm and frog sartorius muscles, phenthonium (Phen, 1-100 mu M) depressed the muscle twitches elicited by nerve stimulation (IC50: 23 mu M and 5 mu M, respectively), and blocked the nerve-evoked muscle action potential. the neuromuscular blockade was not reversed after incubation with neostigmine.3 Equal concentrations of Phen decreased the rate of rise and prolonged the falling phase of the directly elicited action potential in frog sartorius muscle fibres, indicating that the drug also affects the sodium and potassium conductance.4 Phen (50 and 100 mu M) protected the ACh receptor against alpha-bungarotoxin (BUTX) blockade in the mouse diaphragm allowing recording of endplate potentials and action potentials after 5 h wash with physiological salt solution.5 Phen (10-100 mu M) produced a concentration- and voltage-dependent decrease of the endplate current (e.p.c.), and induced nonlinearity of the current-voltage relationship. At high concentrations Phen also shortened the decay time constant of e.p.c (tau(e.p.c.)) and reduced its voltage sensitivity.6 At the same range of concentrations, Phen also reduced the initial rate of [I-125]-BUTX binding to junctional ACh receptors of the rat diaphragm (apparent dissociation constant = 24 mu M), the relationship between the degree of inhibition and antagonist concentration being that expected for a competitive mechanism.7 It is concluded that Phen affects the electrical excitability of the muscle fibre membrane, and blocks neuromuscular transmission through a mechanism that affects the agonist binding to its recognition site and ionic channel conductance of the nicotinic ACh receptor.en
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, Div Cellular Pharmacol, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Ribeirao Preto, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, Div Cellular Pharmacol, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Ribeirao Preto, SP, Brazil
dc.description.sourceWeb of Science
dc.format.extent1270-1276
dc.identifierhttp://dx.doi.org/10.1038/sj.bjp.0701932
dc.identifier.citationBritish Journal of Pharmacology. Basingstoke: Stockton Press, v. 124, n. 6, p. 1270-1276, 1998.
dc.identifier.doi10.1038/sj.bjp.0701932
dc.identifier.issn0007-1188
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/25917
dc.identifier.wosWOS:000074965000034
dc.language.isoeng
dc.publisherStockton Press
dc.relation.ispartofBritish Journal of Pharmacology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectnicotinic receptoren
dc.subjectnoncompetitive blockeren
dc.subjectionic channelen
dc.subjectendplate currenten
dc.subjectmuscarinic antagonisten
dc.titleMechanism of neuromuscular blockade induced by phenthonium, a quaternary derivative of (-)-hyoscyamine, in skeletal musclesen
dc.typeinfo:eu-repo/semantics/article
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