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Research ArticleArticle

SITES OF ACTION OF SKF 525-A IN NERVE AND MUSCLE

G. SUAREZ-KURTZ and C. PAUL BIANCHI
Journal of Pharmacology and Experimental Therapeutics March 1970, 172 (1) 33-43;
G. SUAREZ-KURTZ
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C. PAUL BIANCHI
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Abstract

The pK. of SKF 525-A was determined, and the effects of the drug on nerve conduction and on the excitation-contraction coupling in striated muscle were studied on isolated preparations of the frog. In both sheathed and desheathed sciatic nerve, the amplitude of the action potential was reduced by SKF 525-A. In the desheathed nerve, the block was greater at pH 6.8 than at pH 7.8; this indicates that the ionized form of the drug, when bound to the nerve membrane, is more effective in blocking excitability than the free base. SKF 525-A depressed the muscle twitch of both the directly and the indirectly stimulated sartorius muscle; this effect was more pronounced on indirect stimulation. The depression of twitch tension in the directly stimulated sartorius was followed by an equivalent reduction in the amplitude of the muscle action potential. In concentrations which depress the action potential in both the sciatic nerve (sheathed and desheathed) and the sartorius muscle, SKF 525-A induced a slight hyperpolarization of the cell membrane. SKF 525-A potentiated the caffeine-induced contracture of the sartorius muscle; this effect was more pronounced at pH 7.2 than at pH 6.2. The contracture of the rectus abdominis muscle produced by calcium removal in the presence of disodium ethylenediamine tetraacetate was also potentiated by SKF 525-A. In both sartorius and rectus abdominis muscles, SKF 525-A blocked the contracture elicited by high potassium without seriously affecting the fall in the demarcation potential of the membrane. The data indicate close similarities between the effects of SKF 525-A and other tertiary amine local anesthetics on nerve conduction and on the excitation-contraction coupling in striated muscle. The significance of the present results in relation to the potentiation and antagonism of neuromuscular blocking agents by SKF 525-A is briefly discussed.

Footnotes

    • Received June 19, 1969.
    • Accepted October 27, 1969.
  • © 1970, by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 172, Issue 1
1 Mar 1970
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Research ArticleArticle

SITES OF ACTION OF SKF 525-A IN NERVE AND MUSCLE

G. SUAREZ-KURTZ and C. PAUL BIANCHI
Journal of Pharmacology and Experimental Therapeutics March 1, 1970, 172 (1) 33-43;

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Research ArticleArticle

SITES OF ACTION OF SKF 525-A IN NERVE AND MUSCLE

G. SUAREZ-KURTZ and C. PAUL BIANCHI
Journal of Pharmacology and Experimental Therapeutics March 1, 1970, 172 (1) 33-43;
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