The effect of levosulpiride on in vitro motor patterns in the human gastric fundus, antrum, and jejunum

Background Levosulpiride is a 5HT(4) agonist/D-2 antagonist prokinetic agent used to improve gastric emptying in patients with functional dyspepsia or gastroparesis. The aim of this study was to characterize its effect on the main in vitro motility patterns in the human fundus, antrum, and jejunum. Methods Circular muscle strips from human stomach (antrum and fundus) and jejunum, obtained from 46 patients undergoing bariatric surgery, were studied using organ baths. Enteric motor neurons (EMNs) were stimulated by electrical field stimulation (EFS). Key Results Levosulpiride, caused an increase in the EFS-induced cholinergic contractions in the gastric antrum (+37 +/- 15.18% at 100 mu M, pEC(50) = 4.46 +/- 0.14; p < 0.05, n = 8) and jejunum (+ 45.4 +/- 22.03% at 100 mu M, pEC(50) = 3.78 +/- 6.81; p < 0.05, n = 5), but not in the gastric fundus. It also caused a slight decrease in tone and frequency of spontaneous contractions in the jejunum, but did not have any major effect on tone or spontaneous contractions in the stomach. It did not have any effect on EFS induced relaxations mediated by nitric oxide (NO) in the stomach (antrum and fundus) and by NO and ATP in the jejunum. Conclusions & Inferences Our results suggest that the prokinetic effects of levosulpiride in humans are mainly due to the facilitation of the release of acetylcholine by enteric motor neurons in the gastric antrum and the jejunum.