The action of flecainide acetate and its enantiomers on mammalian non-myelinated nerve fibres.
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.
Lie-A-Huen
L
L
Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, the Netherlands.
van den Akker
J
J
den Hertog
A
A
Meijer
D K
DK
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005424:Flecainide / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009186:Myelin Sheath / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013237:Stereoisomerism
D012964:Sodium; D005424:Flecainide; D011188:Potassium