Sodium channel blockers alter slow-wave frequency of the rat stomach in vivo.
Treatment with sodium-channel-blocking agents is accompanied by a high incidence of gastrointestinal side effects. We therefore studied the influence of two sodium channel blockers, mexiletine and flecanaide, on gastric and jejunal myoelectrical activity of unanesthetized rats. Bipolar electrodes were implanted chronically on the serosal surface of the antrum or the jejunum of male rats (weight: 250-350 g). Electrical activity was recorded on a Polygraph starting on day 5 after the operation After 1 h of baseline recordings, either vehicle or an active drug was given randomly. Recordings were continued for 4 h after drug administration. Vehicle did not induce changes in slow-wave frequency. In contrast, gastric slow-wave activity significantly decreased after the administration of both mexiletine and flecanaide. Jejunal myoelectrical activity was only slightly affected by sodium channel blockade. The disruption of gastric myoelectrical activity may contribute to the side effects observed during chronic treatment with class I antiarrhythmic drugs.
Bielefeldt
K
K
Center of Health Sciences, School of Pharmacy, Madison, Wisc.
Bass
P
P
D000818:Animals; D004567:Electrodes, Implanted; D005424:Flecainide / Q000494:pharmacology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology
D015222:Sodium Channels; D008801:Mexiletine; D005424:Flecainide