The action of flecainide acetate and its enantiomers on mammalian non-myelinated nerve fibres

Abstract

The effects of flecainide acetate racemate and its two enantiomers on voltage-operated sodium and potassium channels and on the sodium pump activity of non-myelinated fibres of the guinea-pig vagus nerve were studied with the sucrose-gap method. The racemic mixture as well as the R enantiomer and S enantiomer in a concentration range of 3 x 10(-5)-3 x 10(-4) M caused suppression of the compound action potential, a diminished propagation velocity and a reduction of the post-tetanic potential (PTH), which was also observed with lidocaine. There was no significant difference in the effect caused by the enantiomers separately. The R enantiomer tended to evoke a stronger effect compared with the S enantiomer. However, the magnitude of the action is concentration-dependent. At a concentration less than 10(-4) M the action of the racemate was stronger than an equimolar concentration of the enantiomers. The activity of the sodium pump, defined by the time constant of post-tetanic potential decay, was affected at a concentration of 10(-4) M of the racemate, in contrast to lidocaine. The racemate and both enantiomers of flecainide acetate possess a similar local anaesthetic action, as reflected by the inhibition of voltage-operated sodium channels.