Effect of Four Medications Associated with Gastrointestinal Motility on Oddi Sphincter in the Rabbit

Abstract

Aim: Modulatory drugs of gastrointestinal (GI) motility are a possibility for use to relieve the main clinical presentation of sphincter of Oddi (SO) dysfunctions which are not easily distinguished from those occurring in high prevalence functional GI disorders. The aim of this study was to investigate the effects of GI motility modulators including pinaverium, domperidone, trimebutine, and tegaserod on the contractile activity of SO stimulated by carbachol in the rabbit. Methods: The contraction responses precontracted by carbachol (0.1 μM) of in vitro rabbit SO rings were evaluated before and after the addition of a series concentration (10−13 to 10−3 M) of pinaverium, domperidone, trimebutine, and tegaserod. Results: Pinaverium induced a concentrationdependent relaxation of isolated SO rings (10−13 vs. 10−7 vs. 10−13 M = 16.6 ± 4.8 vs. 47.1 ± 5.5 vs. 81.2 8 6.2%, p<0.001 by ANOVA) precontracted with carbachol (0.1μM). Tegaserod did not significantly effect (10−13 vs. 10−7 vs. 10−3 M = 2.3 ± 2.2 vs. 6.7± 2.1 vs. 10.1 ± 2.3%, p>0.05 by ANOVA) SO motility, but domperidone seemed to stimulate SO contractions (1010−12 vs. 1010−7 vs. 1010−3 M = −2.2 ± 1.5 vs. −13.9 ± 2.0 vs. −21.0 ± 2.7%, p<0.05 by ANOVA). At low doses (10−13 to 10−7 M), trimebutine stimulated SO contraction (−8.7 ± 1.4 vs. −9.3 ± 2.0%); however, high doses (10−6 to 10−3 M) of trimebutine inhibited SO motility (−-5.9 ± 1.7 vs. 14.5 ±2.0%, p<0.05 by ANOVA). Conclusion: Pinaverium totally inhibits contractions induced by carbachol and tegaserod has no effect on carbachol-induced contractions. Domperidone stimulates contractions induced by carbachol. Trimebutine could either stimulate or inhibit SO contractions depending on its dosage.