Investigation into the Effects of Mosapride on Motility of Guinea Pig Stomach, Ileum, and Colon

Abstract

Mosapride citrate (Mosapride) is a new prokinetic agent that enhances the gastrointestinal (GI) motility by stimulation of 5-HT4 receptors. This agent stimulates acetylcholine release from enteric cholinergic neurons in the GI wall. It was reported in several studies that mosapride selectively enhanced the upper, but not lower, GI motor activity. However, in these studies other 5-HT4 receptor agonists exerted stimulating effects on the motility of the colon. Moreover, it is well known that the receptors of 5-HT4 are also located in the colon. The purpose of this study was to estimate the effect of mosapride on the motility of the stomach, ileum and colon in the guinea pig and to investigate whether or not mosapride influenced the colonic motility. Mosapride significantly increased the amplitude of the contraction waves in the guinea pig stomach by electrical stimulation. In addition, it significantly increased the number of peaks, the area under the curve and the propagation velocity of the peristaltic contraction of the guinea pig ileum in a concentration dependent fashion. Mosapride also significantly shortened the transit time of the guinea pig colon. Accordingly, we concluded that mosapride exerted prokinetic effect on the entire GI tract of the guinea pig. Based on the possibility of similar results in humans, we suggest the potential use of mosapride for lower GI motor disorders such as constipation and upper GI motor disorders such as gastroesophageal reflex disease or gastroparesis.

The Pharmacology of TD-8954, a Potent and Selective 5-HT4 Receptor Agonist with Gastrointestinal Prokinetic Properties

“…Following TD-8954 administration and injection of carmine red dye into the proximal colon, the time for excretion of the first fecal pellet containing the marker was markedly reduced. The potent prokinetic activity of TD-8954 in this guinea pig model is in keeping with the proposed role of 5-HT and 5-HT 4 receptor activation in promoting GI motility (Muller-Lissner, 1987; Jin et al, 1999; Briejer et al, 2001b; Ji et al, 2003). The TD-8954-induced relaxation of the rat esophagus in this study is also consistent with agonist activity at the 5-HT 4 receptor (Triggle et al, 1988; Reeves et al, 1991).…”

“…The GI prokinetic activity of 5-HT 4 receptor agonists, such as tegaserod (Zelnorm ® ), cisapride (Propulsid ® ), velusetrag (TD-5108), prucalopride (Resolor ® ), and mosapride has been demonstrated in a variety of species (Jin et al, 1999; Briejer et al, 2001b; Inui et al, 2002; Ji et al, 2003; Manini et al, 2009), and clinical efficacy has been established in patients with irritable bowel syndrome with constipation (IBS-C), chronic idiopathic constipation, functional dyspepsia, or gastroparesis (Deruyttere et al, 1987; Muller-Lissner, 1987; Abell et al, 1991; Camilleri, 2001; Johanson, 2004; Patel et al, 2004; Camilleri et al, 2008; Goldberg et al, 2010). Cisapride and tegaserod were used widely to treat upper and lower GI disorders of reduced motility, respectively, although their clinical efficacy in many patients was modest (Kellow et al, 1995; Evans et al, 2004), possibly reflecting their interactions with receptors other than the 5-HT 4 subtype (Briejer et al, 1995; Beattie et al, 2004; Beattie and Smith, 2008; De Maeyer et al, 2008).…”

Effects of the Addition of Mosapride to Gastroesophageal Reflux Disease Patients on Proton Pump Inhibitor: A Prospective Randomized, Double-blind Study

“…23,[33][34][35] In this study, PPI treatment was associated with significant delays in gastric emptying by 53.9% prolongation in T 1/2 compared to baseline which was slightly higher than the previous report with 15-40% delay in T 1/2 during PPI treatment. 5,36 However, with mosapride added to PPI, the delayed gastric emptying did not occurr. The delaying effect of PPI on gastric emptying appears to be manifested by the increase in percentage of meal retained at 30, 60 and 90 minutes compared with pre-treatment baseline values.…”

Exploration of Antiemetics for Osteoporosis Therapy-Induced Nausea and Vomiting Using PET Molecular Imaging Analysis to Gastrointestinal Pharmacokinetics

“…Interestingly, mosapride and prochlorperazine slightly restored the gastrointestinal motility of [ 18 F]FDG. Mosapride is a selective 5-HT 4 receptor agonist that facilitates the release of locally endogenous acetylcholine and is thought to selectively stimulate upper, but not lower, GI motility, and to have no effects on the central nervous system (CNS) (27)(28)(29). The mechanism of action of prochlorperazine has not been fully determined, but has been attributed to dopamine and histamine blockade in the chemoreceptor trigger zone (19,20,30).…”