Cuiping Li1, Wei Qian, Xiaohua Hou. 1. Division of Gastroenterology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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 microM) 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 concentration-dependent relaxation of isolated SO rings (10(-13) vs. 10(-7) vs. 10(-3)M = 16.6 +/- 4.8 vs. 47.1 +/- 5.5 vs. 81.2 +/- 6.2%, p < 0.001 by ANOVA) precontracted with carbachol (0.1 microM). 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 (10(-12) vs. 10(-7) vs. 10(-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. Copyright 2009 S. Karger AG, Basel.
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 microM) 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 concentration-dependent relaxation of isolated SO rings (10(-13) vs. 10(-7) vs. 10(-3)M = 16.6 +/- 4.8 vs. 47.1 +/- 5.5 vs. 81.2 +/- 6.2%, p < 0.001 by ANOVA) precontracted with carbachol (0.1 microM). 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 (10(-12) vs. 10(-7) vs. 10(-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. Copyright 2009 S. Karger AG, Basel.