Effects of a 5‐hydroxytryptamine3 receptor antagonist (ICS 205‐930) on colonic motor activity in healthy men.

Stacher, G; Gaupmann, G; Schneider, Christa; Stacher-Janotta, Giselheid; Steiner-Mittelbach, G; Abatzi, Thalia-Anthi; Steinringer, H

doi:10.1111/j.1365-2125.1989.tb05432.x

Cited by 15 publications

(12 citation statements)

References 14 publications

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“…In healthy subjects a single intravenous dose of a 5-HT3 antagonist, ICS 205-930, causes a significant change in the number and amplitude of colonic contractions [21 ]. In a study involving 12 patients with the IBS, single doses of intravenous granisetron, a 5-HTy antagonist, resulted in dose-dependeni reductions in rectal sensitivity to dis tension.…”

Section: Introductionmentioning

confidence: 99%

Modification of Visceral Sensitivity and Pain in Irritable Bowel Syndrome by 5-HT<sub>3</sub> Antagonism (Ondansetron)

et al. 1996

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Intrinsic neurons containing serotonin (5-HT) are involved in the regulation of gastrointestinal motor function and are also thought to be important in the modulation of visceral sensory function. We have evaluated the effect of a specific 5-HT3 antagonist (ondansetron, O) on visceral sensation and rectal compliance in a randomized, double-blind, cross-over, placebo (P) controlled study of·16 mg 3 times/day, in healthy volunteers and patients with irritable bowel syndrome (IBS). Symptoms were also evaluated in the latter group. A 2-week run-in period was followed by two 2-week treatment arms of P and O, separated by a 2-week wash-out period. Twelve healthy subjects and 9 patients with IBS were recruited. Assessment was by daily symptom and bowel function diary, and physiological tests of anal manometry, rectal sensory testing to distension and electrical stimulation, and rectal compliance. Ten healthy subjects completed the entire study, and 6 IBS patients completed the diary card evaluation, including 5 who also completed the physiological evaluation.·caused significantly (p < 0.01) firmer stools when considering both subject groups together. In the healthy subjects no physiological parameters were altered by O. In IBS patients the rectal sensory threshold to electrical stimulation tended to increase with·(20 vs. 28 mA, P vs. O, median, p = 0.06) while the urge (80 vs. 60 ml, p = 0.05) and maximum tolerated volumes (130 vs. 90, p = 0.03) to distension tended to decrease with O. Patients with IBS experienced significantly fewer daily episodes of pain while on·(2 vs. 1, p = 0.03). Serotonin-3 antagonism (O) causes firmer bowel actions in all subjects, and may affect gut sensitivity and pain in patients with IBS.

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Section: Introductionmentioning

confidence: 99%

Modification of Visceral Sensitivity and Pain in Irritable Bowel Syndrome by 5-HT<sub>3</sub> Antagonism (Ondansetron)

et al. 1996

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“…This compound enhances gastric emptying of glass spheroids in conscious guinea pigs with a stomach made atonic by fasting (Buchheit et al, 1985a) and of liquids as well as of solids in rats (Buchheit etal., 1989; Gidda etal., 1988) and reverses cisplatin induced slowing of gastric emptying in fed rats (Eeckhout & Vedder, 1988). In healthy man, ICS 205-930 has been reported to accelerate gastric emptying of a solid meal (Akkermans etal., 1988;McCallum et al, 1989), to accelerate (Meleagros et al, 1987) or not to influence (McCallum et al, 1989) mouth-to-caecum transit of ingesta, and to increase the motor activity of the left colon in the fasting as well as in the postprandial state and after stimulation with neostigmine (Stacher et al, 1989 Lilja et al, 1982;Maton et al, 1982) or intraduodenal instillation (Lamers et al, 1979;Lilja et al, 1982) of fat. Such a mechanism is also suggested by the fact that gastric emptying is delayed at plasma levels of exogenous cholecystokinin which equate with those prevailing after the ingestion of a mixed meal (Liddle et al, 1985).…”

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confidence: 99%

“…This compound enhances gastric emptying of glass spheroids in conscious guinea pigs with a stomach made atonic by fasting (Buchheit et al, 1985a) and of liquids as well as of solids in rats (Buchheit etal., 1989;Gidda etal., 1988) and reverses cisplatin induced slowing of gastric emptying in fed rats (Eeckhout & Vedder, 1988). In healthy man, ICS 205-930 has been reported to accelerate gastric emptying of a solid meal (Akkermans etal., 1988;McCallum et al, 1989), to accelerate (Meleagros et al, 1987) or not to influence (McCallum et al, 1989) mouth-to-caecum transit of ingesta, and to increase the motor activity of the left colon in the fasting as well as in the postprandial state and after stimulation with neostigmine (Stacher et al, 1989). Furthermore, Correspondence: Professor Dr G. Stacher, Psychophysiologisches Laboratorium, Wahringer Gtirtel 18-20, A-1090 Wien, Austria found to reduce stool frequency in some patients with the carcinoid syndrome (Anderson et al, 1987) and to prevent cisplatin-induced emesis not only in the ferret (Costall et al, 1986) but also in man (Leibundgut & Lancranjan, 1987).…”

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confidence: 99%

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

Stacher

Bergmann

Schneider

et al. 1990

Brit J Clinical Pharma

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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.

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“…Therefore, antagonism of the 5-HT 3 receptors may be useful in treating functional bowel disease because of their possible inhibitory activity on hypermotility and /or hypersensitivity. In this study, while granisetron strongly inhibited many kinds of diarrhea, it decreased stool output in naive rats, supporting that constipation tend to result from the clinical use of 5-HT3-receptor antagonists (38,39).…”

Section: Discussionmentioning

confidence: 73%

Laxative and Anti-diarrheal Activity of Polycarbophil in Mice and Rats

Saito

Mizutani

Iwanaga

et al. 2002

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the laxative and anti-diarrheal activity of polycarbophil, an insoluble hydrophilic polymer, in comparison with other agents used for treating functional bowel disorder (FBD). In naive rats, polycarbophil (500 mg /kg) increased fecal weight and water contents without producing diarrhea. Carboxymethylcellulose (CMC) did not produce evident changes in bowel movement. Picosulfate markedly produced diarrhea. Loperamide, trimebutine and granisetron decreased stool output dose-dependently. Constipation, indicated by decrease in fecal weight, was produced by loperamide and clonidine in rats. Polycarbophil (500 mg /kg) and CMC increased fecal weight without diarrhea. Conversely trimebutine further decreased fecal weight in constipated rats. Polycarbophil (500 mg /kg) suppressed diarrhea induced by castor oil, and at 250 -500 mg /kg, it produced shaped stools in animals with stools loosened by prostaglandin E2, serotonin or carbachol in mice. Polycarbophil (500 mg /kg) also reduced stools in rats with stool output increased by wrap restraint stress (WRS). CMC had no effect in the diarrhea models, except for carbachol-induced diarrhea, and WRS-induced evacuation. Loperamide, trimebutine and granisetron inhibited diarrhea production and WRS-induced evacuation, except for carbachol-induced diarrhea. The results show that polycarbophil prevents constipation and diarrhea without inducing diarrhea or constipation, which is different from the other agents. Hydrophilic polymers such as polycarbophil will be promising agents for the treatment of FBD.

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Effects of a 5‐hydroxytryptamine3 receptor antagonist (ICS 205‐930) on colonic motor activity in healthy men.

Cited by 15 publications

References 14 publications

Modification of Visceral Sensitivity and Pain in Irritable Bowel Syndrome by 5-HT<sub>3</sub> Antagonism (Ondansetron)

Modification of Visceral Sensitivity and Pain in Irritable Bowel Syndrome by 5-HT<sub>3</sub> Antagonism (Ondansetron)

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

Laxative and Anti-diarrheal Activity of Polycarbophil in Mice and Rats

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