Effects of the 5‐HT3 receptor antagonist ICS 205‐930 on fat‐delayed gastric emptying and antral motor activity.

Abstract

1. The selective 5‐HT3 receptor antagonist, ICS 205‐930 (Sandoz), has been reported to have potent effects on gastric smooth muscle in vivo and to enhance gastric emptying in animals and in man. 2. This study investigated the effects of ICS 205‐930 on fat‐delayed gastric emptying of a semisolid meal and antral motor activity in humans. 3. Twelve healthy men participated in each of three studies in which 10 or 20 mg of ICS 205‐930 or placebo were infused i.v. in a random double‐blind fashion. Gastric emptying and antral motor activity were studied scintigraphically. 4. Gastric emptying was not altered after 10 mg but slower after 20 mg of ICS 205‐930 than after placebo. Emptying after 20 mg of ICS 205‐930 was significantly slower than after 10 mg of ICS 205‐ 930. 5. Antral contraction amplitude was slightly lower after 20 mg of ICS 205‐930 than after placebo, whereas the effects of 10 mg ICS 205‐ 930 did not differ from those of placebo. 6. The results suggest that the investigated doses of ICS 205‐930 have only slight effects on gastric motor activity of healthy young men, with 20 mg reducing the rate of emptying.

Effects of Ramosetron on Gastrointestinal Transit of Guinea Pig

“…On the other hand, Talley et al29 reported that ondansetron, a selective 5-HT 3 RA, did not significantly alter small intestine transit and oral to cecal transit time in healthy volunteers. Troisetron, a selective 5-HT 3 RA, has been found to either modestly increase gastric emptying or reduce it in healthy volunteers 30. The action of 5-HT 3 RAs to modify contraction-relaxation responses would be dependent on the relative balance of excitatory-inhibitory tone 17,23.…”

Does intravenous ondansetron affect gastric emptying of a solid meal, gastric electrical activity or blood hormone levels in healthy volunteers?

“…Indeed, in animal studies, tropisetron abolishes various intestinal effects of 5‐HT 4 agonists 36 , 47–49 and, in healthy volunteers, Stacher et al . found a further increase in fat‐induced delayed gastric emptying by intravenous tropisetron, 20 mg, compared to 10 mg which did not differ from placebo 21 . In contrast to tropisetron, ondansetron has a very weak affinity to other receptors, such as 5‐HT1c, α1 and μ opioid receptors, which is probably without any clinical relevance 5 , .…”

“…Some investigators have found an accelerated gastric emptying, 14 , 15 but others have not, 16–19 or even demonstrated an opposite effect of 5‐HT 3 receptor antagonists 20 , . 21 …”

“…It has been suggested that the anti‐emetic effect of 5‐HT 3 may not only be due to suppression of nausea and the vomiting reflex, but also to direct or indirect effects on gastric motility. Although evidence for this latter assumption has been found in several animal studies, 9–13 the results from human studies with various 5‐HT 3 receptor antagonists are equivocal 14–21 …”

Subpopulations of Gastric Myenteric Neurons Are Differentially Activated via Distinct Serotonin Receptors: Projection, Neurochemical Coding, and Functional Implications

“…Acceleration (Buchheit et al, 1985;Akkermans et al, 1988), delay (Stacher et al, 1990), and no effect have been reported (Mawe et al, 1989;Gershon et al, 1990). In part, the different results could be explained by the nutrient content of the meal, indicating that 5-HT 3 receptors located on primary afferent nerve fibers and centrally controlled reflexes are involved (Read and G wee, 1994).…”