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. 1995 Jul;115(5):787–794. doi: 10.1111/j.1476-5381.1995.tb15002.x

Effects of the two enantiomers, S-16257-2 and S-16260-2, of a new bradycardic agent on guinea-pig isolated cardiac preparations.

O Pérez 1, P Gay 1, L Franqueza 1, R Carrón 1, C Valenzuela 1, E Delpón 1, J Tamargo 1
PMCID: PMC1908524  PMID: 8548178

Abstract

1. The electromechanical effects of two enantiomers, S-16257-2 (S57) and S-16260-2 (R60), were studied and compared in guinea-pig isolated atria and ventricular papillary muscles. The possible stereoselectivity of the interaction on the cardiac Na+ channel was analysed by comparing the effects of the two enantiomers on the onset and recovery kinetics of the frequency-dependent Vmax block. 2. In spontaneously beating right atria, S57 and R60 (10(-8)M-10(-4M) exerted a negative chronotropic effect (pIC50 = 5.07 +/- 0.19 and 4.76 +/- 0.18, respectively) and prolonged the sinus node recovery time, this effect being more marked with S57. In electrically driven left atria, S57 decreased (P < 0.05) contractile force only at 10(-4M) and R60 at concentrations > or = 5 x 10(-5M), whereas in papillary muscles the negative inotropic effect appeared at concentrations > 10(-5M). 3. In papillary muscles driven at 1 Hz, S57 and R60 at concentrations higher than 5 x 10(-6M) produced a concentration-dependent decrease in the maximum upstroke velocity (Vmax) and amplitude of the cardiac action potential without altering the resting membrane potential or the action potential duration. S57 and R60 had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular muscle fibres depolarized in high K+ (27 mM) solution. 4. At 5 x 10(-5M), S57 and R60 produced a small tonic Vmax block. However, in muscles driven at rates between 0.5 and 3 Hz both enantiomers produced an exponential decline in Vmax (frequency-dependent Vmax block) which augmented at higher rates of stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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