Pranlukast, a leukotriene receptor antagonist, prolongs the duration of the migrating motor complex in dogs.
Current information on the effects of leukotriene receptor antagonists on gastrointestinal motility and their mechanisms of gastrointestinal side effects are unknown. Our study aimed to answer the question whether the leukotriene inhibition induced by Pranlukast alters the normal gastrointestinal contraction patterns, and whether any motility abnormalities found explain the gastrointestinal side effects of these types of medications. Seven dogs were used after implanting force transducers in the body and antrum of the stomach, duodenum, and jejunum to monitor gastrointestinal motility. Pranlukast was given orally to each dog at the end of the migrating motor complex during fasting experiments and 30 min after a standard meal during the fed stage, with continuous monitoring. The migrating motor complex was significantly prolonged, especially during phase I of 208.5 +/- 15.4 min (P < 0.05) at 30 mg/kg and of 280.3 +/- 12.5 min (P < 0.05) at 60 mg/kg, compared with controls (93.5 +/- 5.5 min). A significant reduction in the postprandial motility index was also noticed at 60 mg/kg (445.20 +/- 31.30 g x min; P < 0.001) compared to controls (728.20 +/- 26.76 g x min). In conclusion, we are the first to demonstrate that Pranlukast produces a significant inhibitory effect on gastrointestinal motility, which could explain in part some of the side effects observed with these types of drugs.
Garcia
Moises
M
Department of Surgery, Gunma University School of Medicine, 3-39-22 Showamachi, Maebashi 371-8511, Japan. moises.garcia@aurora.org
Nakabayashi
Toshihiro
T
Mochiki
Erito
E
Haga
Norihiro
N
Pacheco
Ivan
I
Suzuki
Tomoaki
T
Kuwano
Hiroyuki
H
D000818:Animals; D002867:Chromones / Q000627:therapeutic use*; D004285:Dogs; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D020024:Leukotriene Antagonists / Q000627:therapeutic use*; D015289:Leukotrienes / Q000502:physiology; D008297:Male; D016065:Myoelectric Complex, Migrating / Q000187:drug effects*; D019518:Postprandial Period / Q000502:physiology; D013997:Time Factors
D002867:Chromones; D020024:Leukotriene Antagonists; D015289:Leukotrienes; C047681:pranlukast