Mexiletine inhibits nonadrenergic noncholinergic lower oesophageal sphincter relaxation in rabbits

Atsushi Kohjitani, Takuya Miyawaki, Makoto Funahashi, Yoshihiro Mitoh, Ryuji Matsuo, Masahiko Shimada

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Nonadrenergic noncholinergic (NANC) nerves are known to be nitrergic and to have an important role in the regulation of gastrointestinal motility and function. Cardiac antiarrhythmic therapy in humans is accompanied by a high incidence of gastrointestinal side-effects. We investigated the effect of mexiletine, a class Ib antiarrhythmic drug, on NANC lower oesophageal sphincter relaxation. Mexiletine concentration dependently inhibited the NANC relaxation induced by 30 mM KCl (EC50=4.4×10-6 M); the production of 3′,5′-cyclic guanosine monophosphate (cGMP) after KCl stimulation was concentration dependently decreased. The relaxation induced by the exogenous nitric oxide (NO) donor, diethylamine NONOate (10-5 M), was not inhibited by mexiletine, and the cGMP production after diethylamine NONOate application was not altered. Mexiletine did not alter the activity of NO synthase. These findings suggest that mexiletine inhibits NANC relaxation via NO-cGMP pathway modulation, possibly by inhibiting myenteric nitrergic neurotransmission in the lower oesophageal sphincter in rabbits.

Original languageEnglish
Pages (from-to)145-151
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number1-2
Publication statusPublished - Mar 28 2003


  • 3′,5′-Cyclic guanosine monophosphate
  • Lower
  • Mexiletine
  • Nitric oxide (NO)
  • Nitric oxide (NO) synthase
  • Oesophageal sphincter
  • Smooth muscle

ASJC Scopus subject areas

  • Pharmacology


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