STRUCTURE-ACTIVITY RELATIONSHIP FOR GRAYANOTOXIN DERIVATIVES IN FROG SKELETAL-MUSCLE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 217  (3) , 812-819
Abstract
In the presence of biologically active grayanotoxins, the frog skeletal muscle fiber generated a spontaneous action potential which was followed by a sustained depolarization. This depolarization was due to the specific increase in the membrane permeability to Na, as it was abolished by withdrawal of NA from the external medium or application of 1 .times. 10-6 M tetrodotoxin. Potencies of biological activity of 34 grayanotoxin analogs were estimated from the measurement of critical concentrations for spontaneous generation of a prolonged action potential. The biological activity of grayanotoxins was largely dependent on both stereospecificity and hydrophobicity of the molecules. The essential groups in the grayanotoxin molecules for the biological activity were 3.beta.-OH or 2.beta.,3.beta.-epoxy group, 5.beta.-OH, 6.beta.-OH and 10.beta.-methyl groups. There was an optimal hydrophobicity of the molecule for the maximal biological activity. Four essential groups corresponding to those in the grayanotoxin molecules are present in the molecules of veratridine, batrachotoxin and aconitine, all of which are known to keep the Na channel open.

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