Effects of Tropisetron, a 5-HT₃ Receptor Antagonist, on Proximal Gastric Motor and Sensory Function in Nonulcer Dyspepsia

Abstract

Background: Visceral hypersensitivity is claimed to be involved in the pathogenesis of nonulcer dyspepsia (NUD). In a double-blind crossover study, we evaluated the effects of tropisetron, a 5-HT₃ receptor antagonist, on gastric accommodation, reflex relaxation, and sensitivity in NUD patients. Methods: Eight patients and 10 healthy controls received placebo or 5 mg tropisetron on separate days. On each day, gastric accommodation and relaxation were investigated using a gastric barostat. The perception during gastric distension and relaxation was scored by a verbal perception score. Results: Under both medications, gastric accommodation and postprandial gastric reflex relaxation were not impaired in the NUD patients. The visceral perception was increased in the NUD patients and not substantially influenced by tropisetron. Conclusions: Tropisetron does not influence gastric accommodation, reflex relaxation, or gastric sensitivity in NUD patients and healthy controls.

Kynurenine pathway metabolism and the microbiota-gut-brain axis

“…Around 95% of the body's 5-HT is located within the GI tract, primarily synthesised by enterochromaffin cells, and 5% in the CNS (Camilleri, 2002;Gershon and Tack, 2007;Mayer et al, 2001). In healthy humans, other mammals and in disease states, 5-HT in the GI tract is involved in a range of largely reflexive functions including motility (Chial et al, 2003;Gorard et al, 1994), secretion and absorption (Bearcroft et al, 1997), intestinal transit (Wilmer et al, 1993) and colonic tone (Klatt et al, 1999;Talley et al, 1990). In addition, 5-HT mediates feelings of nausea and can induce vomiting by stimulating 5-HT3 receptors on vagal afferent pathways which signal to the nucleus tractus solitarii (Klatt et al, 1999;Talley et al, 1990).…”

“…In healthy humans, other mammals and in disease states, 5-HT in the GI tract is involved in a range of largely reflexive functions including motility (Chial et al, 2003;Gorard et al, 1994), secretion and absorption (Bearcroft et al, 1997), intestinal transit (Wilmer et al, 1993) and colonic tone (Klatt et al, 1999;Talley et al, 1990). In addition, 5-HT mediates feelings of nausea and can induce vomiting by stimulating 5-HT3 receptors on vagal afferent pathways which signal to the nucleus tractus solitarii (Klatt et al, 1999;Talley et al, 1990). In addition, peripheral 5-HT release in the GI tract can modulate food intake by stimulating vagal afferent pathways (Donovan and Tecott, 2013) and inhibition of peripherial 5-HT synthesis has been shown to reduce obesity and metabolic dysfunction through actions on brown adipose tissue thermogenesis (Crane et al, 2015).…”

Spinal NMDA NR1 subunit expression following transient TNBS colitis

“…Central sensitization is characterized by enlarged neuronal receptive fields, allodynia and hyperalgesia (Baranauskas & Nistri 1998; Dubner & Ruda1992 Ma & Woolf 1995; McRoberts et al 2001; petrenko et al 2003; Ren & Dubner 1999; Urban & Gebhart 1999a; Willert et al 2004; Woolf & Thompson 1991). Further support for NMDA receptor-mediated central sensitization and chronic visceral pain is evidenced by attenuation of central sensitization with NMDA receptor antagonists (Castroman & Ness 2002; Dubner & Ruda1992 ; Klatt et al 1999; Sun et al 1998; Traub et al 2002). …”

Functional Dyspepsia: Motor Abnormalities, Sensory Dysfunction, and Therapeutic Options

“…Other selective 5-HT 3 -receptor antagonists, such as tropisetron, alosetron, and ondansetron, have also been studied. In FD patients and healthy controls, tropisetron did not reduce gastric compliance or sensitivity (102). Alosetron and ondansetron had no effect on gastric compliance and perception in small studies of healthy volunteers (103,104).…”