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Effects of a new 1,3-thiazole Derivative ZSY-39 on force of contraction and cyclic AMP content in canine ventricular muscle

  • Experimental Pharmacology
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Summary

A newly synthesized 1,3-thiazole derivative ZSY-39 increased the force of contraction in a concentrationdependent manner in association with elevation of tissue cyclic AMP levels in the isolated canine ventricular trabeculae electrically driven at 0.5 Hz at 37°C. ZSY-39 shortened the duration of isometric contractions mainly by abbreviation of the relaxation time. The maximal response to and EC50 of ZSY-39 were 0.7 (isoproterenol=1.0) and 4.6×10−5 M. Bupranolol (3×10−7 M) did not affect the positive inotropic effect of ZSY-39. The time course of increases in the force of contraction induced by ZSY-39 (10−4 M) coincided with that of cyclic AMP accumulation. The concentration-response curve for the increase in the force of contraction produced by ZSY-39 was superimposable on that of the elevation of cyclic AMP levels. Carbachol (3×10−6 M) shifted the concentration-response curve for the increase in force by ZSY-39 to the right and downward, and decreased the accumulation of cyclic AMP induced by ZSY-39 (10−4 M). ZSY-39 (10−5 M) enhanced significantly the positive inotropic effect of isoproterenol. The relationship between the force of contraction and cyclic AMP levels after the administration of ZSY-39 was not modified by the addition of carbachol or isoproterenol. These findings indicate that cyclic AMP plays an important role in the positive inotropic effect of ZSY-39 on canine ventricular muscle.

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Authors and Affiliations

  1. Department of Pharmacology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, 990-23, Yamagata, Japan

    Masao Endoh MD, Hiroshi Satoh, Ikuo Norota & Katsuhisa Hirano

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  1. Masao Endoh MD
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  2. Hiroshi Satoh
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  3. Ikuo Norota
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  4. Katsuhisa Hirano
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Endoh, M., Satoh, H., Norota, I. et al. Effects of a new 1,3-thiazole Derivative ZSY-39 on force of contraction and cyclic AMP content in canine ventricular muscle. Cardiovasc Drug Ther 4, 1127–1134 (1990). https://doi.org/10.1007/BF01856509

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