(-)-Enantiomer EMD 57439 Antagonizes the Ca^<2+> Sensitizing Effect of (+)-Enantiomer EMD 57033 on Diastolic Function but Not on Systolic Function in Rabbit Ventricular Cardiomyocytes

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Author(s)

Abstract

EMD 53998 (5-[1-(3, 4-dimethoxybenzoyl)-1, 2, 3, 4-tetrahydro-6-quinolyl]-6-methyl-3, 6-dihydro-2<I>H</I>-1, 3, 4-thiadiazin-2-one), the racemic mixture of (+)-enantiomer EMD 57033 and (-)-enantiomer EMD 57439, is a prototype of Ca<SUP>2+</SUP> sensitizers that act via a central and/or down-stream mechanism in cardiac E-C coupling. In rabbit ventricular cardiomyocytes loaded with indo-1/AM, EMD 53998 and EMD 57033 shifted the relationship between Ca<SUP>2+</SUP> transients and cell shortening (systolic function) to the left to the same extent as compared with that of elevation of [Ca<SUP>2+</SUP>]<SUB>o</SUB>. EMD 57439 did not elicit a positive inotropic effect (PIE). The PIE of EMD 57033 was associated with a more pronounced decrease in the diastolic cell length than that of EMD 53998, whereas the systolic effects of these compounds were equivalent. These results indicate that weak phosphodiesterase (PDE) III inhibition may exert a differential action on diastolic and systolic function. Thus, EMD 57439 antagonizes the Ca<SUP>2+</SUP>-sensitizing effect of EMD 57033 on diastolic function with no effect on systolic function, which may lead to a decease in diastolic cell length of a lesser extent with the racemate EMD 53998 compared with (+)-enantiomer EMD 57033.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 80(1), 55-65, 1999-05-01

    The Japanese Pharmacological Society

References:  32

Cited by:  2

Codes

  • NII Article ID (NAID)
    10008194606
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4733125
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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