Comparative pharmacokinetics of (S)-MP3950, a novel 5-HT4 receptor agonist, in normal and atropine-induced gastrointestinal motility disorders rats

Abstract

1. (S)-MP3950 is the (S)-enantiomer of active metabolite of mosapride, which exhibits higher 5-HT receptor agonistic effect than mosapride. It shows promise to become a novel drug candidate for the treatment of gastrointestinal motility disorders (GMDs). However, the pharmacokinetic behavior of (S)-MP3950 in the pathological state of GMDs remains unclear. Herein, we investigated the comparative pharmacokinetics of (S)-MP3950 in normal and GMDs rats. 2. The comparative pharmacokinetics of (S)-MP3950 in normal and atropine-induced GMD rats were studied by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The validated UPLC-MS/MS method was successfully applied to investigate the pharmacokinetic profiles of (S)-MP3950 in normal and atropine-induced GMDs rats. Results showed that comparing to normal rats, C reduced by 73.8%, AUC decreased by 57.6% and AUC declined by 56.8% in model rats. Additionally, the elimination half-life (t) and T were prolonged slightly. 3. The pharmacokinetic results demonstrated that the atropine-induced GMDs reduced the absorption of (S)-MP3950. The pharmacokinetics research in the pathological state might provide more useful information for further study of novel gastric motility candidates.

Metabolomics Analysis of L-Arginine Induced Gastrointestinal Motility Disorder in Rats Using UPLC-MS After Magnolol Treatment

“…The pathogenic factors of gastrointestinal motility disorder are complex. At present, there is no objective criterion for gastrointestinal motility disorder model, but atropine and L-arginine are commonly selected drugs for this model (Ren et al, 2017; Wang et al, 2018). The results of gastric emptying and intestinal propulsion also indicate that L-arginine had inhibited gastric emptying and intestinal propulsion, which indicated that the model of gastrointestinal motility disorder was successful.…”

Prucalopride Inhibits Proliferation of Ovarian Cancer Cells via Phosphatidylinositol 3-Kinase (PI3K) Signaling Pathway

“…Studies have shown that the activation of 5-HT 4 receptor in the cholinergic nerve endings of the enteric nervous system increases the release of acetylcholine in motor neurons, thereby stimulating gastrointestinal motility [ 9 ]. Thus, a new generation of 5-HT 4 receptor agonists is being used for the treatment of gastrointestinal peristalsis disorders [ 10 ]. Studies have found that 5-HT 4 receptors up-regulated the expression of estrogen receptor β in hormone-naive prostates, which may affect the progression of prostate cancer [ 11 ].…”

Weissella paramesenteroides WpK4 ameliorate the experimental amoebic colitis by increasing the expression of MUC‐2 and the intestinal epithelial regeneration

“…Crypts are glandular invaginations located in the intestine that are present in their base intestinal stem cells (ISC). These cells play a fundamental role in intestinal epithelium proliferation and differentiation under physiological and pathological conditions (Perše and Cerar 2012; Wang et al 2018).…”

“…According to some authors, the use of probiotics is capable of stimulating the proliferation and cell regeneration of the GIT (Ribeiro et al 2018; Wang et al 2018). Studies using the cell proliferation markers CDC‐47 and KI67 revealed that there is an increase in these molecules after treatment with conjugated linoleic acid (CLA) and Lactobacillus helveticus and Lactobacillus rhamnosus (Rodrigues et al 2012) .…”

“…In this context, the use of probiotics, living micro‐organisms that confer health benefits when administered in an adequate amount (FAO/WHO 2002), may present as complementary or as an alternative to the current treatment of amoebiasis. The inducing mechanisms of probiotics protection are still being studied but seem to include the toxic and competitive effects against pathogenic species, strengthening of the mucosal barrier and activation of adaptive immunity in the host (Gareau et al 2010; Wang et al 2018). We have observed that the Weissella paramesenteroides strain WpK4 (WpK4), a probiotic candidate bacterium, has protective effects against infections by Salmonella enterica serovar Typhimurium and Giardia lamblia (Alvim et al 2016; Fonseca et al 2019).…”