The effects of granisetron, ICS 205–930 and ondansetron on the visceral pain reflex induced by duodenal distension

Moss, Helen E.; Sanger, Gareth J.

doi:10.1111/j.1476-5381.1990.tb15836.x

Cited by 90 publications

(45 citation statements)

References 20 publications

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“…77 Studies in animals suggest that 5-HT 3 receptors are putative excitatory mediators in visceral sensory pathways; thus, 5-HT 3 antagonists may reduce the level of perception to visceral distension. 88 However, the selective 5-HT 3 antagonists alosetron and ondansetron do not appear to have any significant effects on sensitivity to gastric distension in humans. 89,90 A recent study demonstrated reduction in dyspeptic symptoms in functional dyspepsia patients treated with alosetron.…”

Section: Antinociceptive Agentsmentioning

confidence: 99%

Pathophysiology and Treatment of Functional Dyspepsia

Tack

Lee

2005

Journal of Clinical Gastroenterology

207

247

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Functional dyspepsia is a highly prevalent symptom complex and a heterogenous disorder. Recent studies showed potential associations between specific pathophysiologic disturbances and dyspeptic symptoms. Delayed gastric emptying reported in about 30% of patients with functional dyspepsia is associated with the symptoms of postprandial fullness, nausea, and vomiting. Impaired gastric accommodation present in 40% of functional dyspepsia patients is found to be associated with early satiety. Hypersensitivity to gastric distension is observed in 37% of functional dyspepsia patients and associated with the symptoms of postprandial pain, belching, and weight loss. Psychosocial factors and altered response to duodenal lipids or acid have also been identified as pathophysiologic mechanisms. Therapeutic options are still limited but targeted therapy directed at the underlying pathophysiology seems desirable. Thus, efforts to further elucidate underlying pathophysiologic mechanisms and identify the appropriate patient population using some type of pathophysiologic testing will be required.

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Section: Antinociceptive Agentsmentioning

confidence: 99%

Pathophysiology and Treatment of Functional Dyspepsia

Tack

Lee

2005

Journal of Clinical Gastroenterology

207

247

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“…Studies in the anaesthetized rat using acute levels of noxious colo-rectal or duodenal distension have demonstrated both pressor and depressor blood pressure pseudoaffective reflexes (Ness & Gebhart, 1988; Moss & Sanger, 1990). Of these cardiovascular pseudoaffective reflexes, the depressor response was found to be inhibited by the 5-HT3 receptor antagonists, granisetron and ondansetron, the latter showing only weak activity (Moss & Sanger, 1990;Banner & Sanger, 1991).…”

Section: Introductionmentioning

confidence: 99%

“…Of these cardiovascular pseudoaffective reflexes, the depressor response was found to be inhibited by the 5-HT3 receptor antagonists, granisetron and ondansetron, the latter showing only weak activity (Moss & Sanger, 1990;Banner & Sanger, 1991). As a consequence of these findings, granisetron was tested clinically as a potential visceral analgesic agent since pain and related gastrointestinal sensations are one of the diagnostic features of Irritable Bowel Syndrome (IBS; Thompson et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Differences between 5‐HT₃ receptor antagonists in modulation of visceral hypersensitivity

Banner

Sanger

1995

British J Pharmacology

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Noxious colo‐rectal distension was applied in conscious rats by acute balloon inflation and the effects observed as abdominal muscle contraction with the threshold typically between 10–40 mmHg. The effects of 5‐HT3 receptor antagonists on responses to noxious colo‐rectal distension were then studied in both normal rats and those pretreated with 5‐hydroxytryptophan (5‐HTP). Granisetron and ondansetron (10 μg kg−1 and 1 mg kg−1, s.c.) had no effect on visceromotor thresholds to colo‐rectal distension in normal rats. Hypersensitivity of the colo‐rectum was achieved by systemic administration of a low dose of 5‐HTP (10 mg kg−1, s.c.) which lowered the distension pressure required to induce the visceromotor reflex; analysis of variance showed a highly significant treatment effect (F1,11 = 84.26, P<0.001). Granisetron, zatosetron, bemesetron and renzapride equi‐potently increased the threshold values at which distension evoked a visceromotor reflex after dosing with 5‐HTP, with a maximal response 3.6 to 4.2 fold above saline controls, at 10 μg kg−1, s.c. Metoclopramide (10 μg kg−1) also raised the level of distension required to elicit a response. By comparison, tropisetron caused a small, non‐significant increase in visceromotor threshold values and only at high doses (1 mg kg−1), whilst ondansetron and BRL 46470 had no signficant effects at doses up to 10 mg kg−1. The response to granisetron (10 μg kg−1, s.c.) in 5‐HTP‐treated rats was unaltered by pre‐administration of naloxone (5 mg kg−1, s.c). These results suggest that a 5‐HT3‐like receptor modulates 5‐HTP‐ evoked visceral hypersensitivity. However, the rank order of antagonist potency does not correlate with their order of potency against the classically defined 5‐HT3 receptor.

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“…Hence, there is a potential for 5-HT 3 receptors to modulate distension-induced postprandial changes in blood pressure. In rodents, the decreases in diastolic blood pressure resulting from duodenal distension with intraluminal pressures of 10 -75 cmH 2 O are attenuated by intravenous granisetron in doses of 1-100 g/kg (27).…”

Section: Discussionmentioning

confidence: 99%

Role of 5-hydroxytryptamine mechanisms in mediating the effects of small intestinal glucose on blood pressure and antropyloroduodenal motility in older subjects

Gentilcore

Little²,

Feinle‐Bisset³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Gentilcore D, Little TJ, Feinle-Bisset C, Samsom M, Smout AJ, Horowitz M, Jones KL. Role of 5-hydroxytryptamine mechanisms in mediating the effects of small intestinal glucose on blood pressure and antropyloroduodenal motility in older subjects. Am J Physiol Gastrointest Liver Physiol 293: G692-G698, 2007. First published August 9, 2007; doi:10.1152/ajpgi.00199.2007.-Postprandial hypotension is an important clinical problem, particularly in the elderly. 5-Hydroxytryptamine3 (5-HT3) mechanisms may be important in the regulation of splanchnic blood flow and blood pressure (BP), and in mediating the effects of small intestinal nutrients on gastrointestinal motility. The aims of this study were to evaluate the effects of the 5-HT3 antagonist granisetron on the BP, heart rate (HR), and antropyloroduodenal (APD) motility responses to intraduodenal glucose in healthy older subjects. Ten subjects (5 male, 5 female, aged 65-76 yr) received an intraduodenal glucose infusion (3 kcal/min) for 60 min (t ϭ 0 -60 min), followed by intraduodenal saline for a further 60 min (t ϭ 60 -120 min) on 2 days. Granisetron (10 g/kg) or control (saline) was given intravenously at t ϭ Ϫ25 min. BP (systolic and diastolic), HR, and APD pressures were measured. Pressure waves in the duodenal channel closest ("local") to the infusion site were quantified separately. During intraduodenal glucose, there were falls in systolic and diastolic BP and a rise in HR (P Ͻ 0.0001 for all); granisetron had no effect on these responses. Granisetron suppressed the number and amplitude (P Ͻ 0.05 for both) of local duodenal pressures during intraduodenal glucose. Otherwise, the effects of intraduodenal glucose on APD motility did not differ between study days. We conclude that in healthy older subjects, 5-HT3 mechanisms modulate the local duodenal motor effects of, but not the cardiovascular responses to, small intestinal glucose. heart rate; 5-hydroxytryptamine3; granisetron; intraduodenal glucose; antropyloroduodenal motility POSTPRANDIAL HYPOTENSION, defined as a fall in systolic blood pressure of Ն20 mmHg within 2 h of a meal that is sustained for at least 30 min, is now recognized as a major cause of morbidity and mortality (7, 16) by predisposing to a number of disorders, including syncope, transient ischemic attacks, stroke, and angina (16). Postprandial hypotension occurs more frequently than orthostatic hypotension (16), and those at greatest risk include the elderly and patients with autonomic dysfunction, the latter usually secondary to diabetes (16). Current treatment options are suboptimal.Several factors, including impaired regulation of splanchnic blood flow, the release of gastrointestinal hormones, and duodenal sympathetic nerve activity, have been identified as possible pathophysiological mechanisms in postprandial hypotension (16). The magnitude of the fall in blood pressure is dependent on meal composition; ingestion of carbohydrate, particularly glucose, has been reported to have the greatest suppressive effect on blood pressure (17). Th...

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The effects of granisetron, ICS 205–930 and ondansetron on the visceral pain reflex induced by duodenal distension

Cited by 90 publications

References 20 publications

Pathophysiology and Treatment of Functional Dyspepsia

Pathophysiology and Treatment of Functional Dyspepsia

Differences between 5‐HT₃ receptor antagonists in modulation of visceral hypersensitivity

Role of 5-hydroxytryptamine mechanisms in mediating the effects of small intestinal glucose on blood pressure and antropyloroduodenal motility in older subjects

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The effects of granisetron, ICS 205–930 and ondansetron on the visceral pain reflex induced by duodenal distension

Cited by 90 publications

References 20 publications

Pathophysiology and Treatment of Functional Dyspepsia

Pathophysiology and Treatment of Functional Dyspepsia

Differences between 5‐HT3 receptor antagonists in modulation of visceral hypersensitivity

Role of 5-hydroxytryptamine mechanisms in mediating the effects of small intestinal glucose on blood pressure and antropyloroduodenal motility in older subjects

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Product

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Differences between 5‐HT₃ receptor antagonists in modulation of visceral hypersensitivity