Mechanisms of the Synergistic Interactions between Organic Calcium Channel Antagonists and Various Neuromuscular Blocking Agents

Chang Chuan Chiung, Chiou Lih Chu, Hwang Lin Lin, Huang Chen Yen

Research output: Contribution to journalArticle

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Abstract

Nicardipine, nifedipine, diltiazem and verapamil on the neuromuscular blocking activities of tubocurarine, succinylcholine (SCh), decamethonium and neomycin were studied in isolated mouse phrenic nerve-diaphragm preparations. The effective concentration of SCh for 50% inhibition (IC50) of single indirect twitch responses were reduced markedly by more than 3-fold when the preparations were pretreated with OCA at 10 μM; the latter alone did not appreciably affect the indirect twitch response or the amplitude of miniature endplate potentials. The neuromuscular blocking effect of decamethonium was also enhanced synergistically by OCA to a similar extent. On the other hand, under the comparable condition, the combined uses of OCA plus tubocurarine or neomycin, neomycin plus tubo curarine or SCh, and Mn2+ plus tubocurarine, SCh or neomycin all resulted in insignificant potentiation. These results suggest that OCA have a specific effect to enhance the agonist effect of depolarizing agents on nicotinic acetylcholine receptors. Nicardipine at 2 μM non-competitively inhibited depolarizations of endplates elicited by SCh and decamethonium and abolished them completely at 10 μM nicardipine. The IC50's in inhibiting endplate potentials and miniature endplate potentials by SCh and decamethonium were also reduced 2 to 3.5-fold by nicardipine. It is inferred that OCA are endowed with a unique capability to allosterically affect the postsynaptic nicotinic acetylcholine receptor, promoting its desensitization liability, hence synergistic interaction with depolarizing agents. Presynaptic effects of OCA are probably not involved.

Original languageEnglish
Pages (from-to)285-292
Number of pages8
Journalthe japanese journal of pharmacology
Volume53
Issue number3
DOIs
Publication statusPublished - Jan 1 1990
Externally publishedYes

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Neuromuscular Blocking Agents
Succinylcholine
Calcium Channel Blockers
Nicardipine
Neomycin
Tubocurarine
Nicotinic Receptors
Inhibitory Concentration 50
Neuromuscular Agents
Phrenic Nerve
Diltiazem
Nifedipine
Verapamil
Diaphragm
decamethonium

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mechanisms of the Synergistic Interactions between Organic Calcium Channel Antagonists and Various Neuromuscular Blocking Agents. / Chuan Chiung, Chang; Lih Chu, Chiou; Lin Lin, Hwang; Chen Yen, Huang.

In: the japanese journal of pharmacology, Vol. 53, No. 3, 01.01.1990, p. 285-292.

Research output: Contribution to journalArticle

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