Drug-induced modification of ionic conductance at the neuromuscular junction

J. J. Lambert, N. N. Durant (Lead / Corresponding author), Edward G. Henderson

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

As an experimental probe, the alteration of ACh receptor channel kinetics by ACh channel blockers has provided a better understanding of the ACh receptor channel complex. The diverse chemical structures of the drugs that interact with the ACh ionic channel suggests that in comparison to the stereospecificity of the ACh recognition site of the receptor the ionic channel is relatively nonspecific. Agonists and antagonists may bind to a common recognition site on the ACh receptor; however, it appears that several channel blocker binding sites (distinct from the recognition site) exist. The safety factor for neuromuscular transmission makes it unlikely that Ach channel blockade alone will block neuromuscular transmission, although in some cases it may provide an explanation for drug interactions and drug side effects. Block of neurotransmitter-activated channels by several agents at other synapses has been observed, although the contribution of channel blockade by these agents to their therapeutic and pharmacological effects remains to be determined.

Original languageEnglish
Pages (from-to)505-539
Number of pages35
JournalAnnual Review of Pharmacology and Toxicology
Volume23
DOIs
Publication statusPublished - 1 Jan 1983

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Neuromuscular Junction
Cholinergic Receptors
Ion Channels
Drug interactions
Pharmaceutical Preparations
Neuromuscular Blockade
Safety factor
Therapeutic Uses
Drug-Related Side Effects and Adverse Reactions
Drug Interactions
Synapses
Neurotransmitter Agents
Binding Sites
Pharmacology
Safety
Kinetics

Cite this

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Drug-induced modification of ionic conductance at the neuromuscular junction. / Lambert, J. J.; Durant, N. N. (Lead / Corresponding author); Henderson, Edward G.

In: Annual Review of Pharmacology and Toxicology, Vol. 23, 01.01.1983, p. 505-539.

Research output: Contribution to journalArticle

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AB - As an experimental probe, the alteration of ACh receptor channel kinetics by ACh channel blockers has provided a better understanding of the ACh receptor channel complex. The diverse chemical structures of the drugs that interact with the ACh ionic channel suggests that in comparison to the stereospecificity of the ACh recognition site of the receptor the ionic channel is relatively nonspecific. Agonists and antagonists may bind to a common recognition site on the ACh receptor; however, it appears that several channel blocker binding sites (distinct from the recognition site) exist. The safety factor for neuromuscular transmission makes it unlikely that Ach channel blockade alone will block neuromuscular transmission, although in some cases it may provide an explanation for drug interactions and drug side effects. Block of neurotransmitter-activated channels by several agents at other synapses has been observed, although the contribution of channel blockade by these agents to their therapeutic and pharmacological effects remains to be determined.

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