The 5‐HT4 receptor agonist, tegaserod, is a potent 5‐HT2B receptor antagonist in vitro and in vivo

Beattie, David T.; Smith, Jacqueline A.; Marquess, Daniel G.; Vickery, Ross G.; Armstrong, Scott R.; Pulido-Rios, T; McCullough, Julia L.; Sandlund, C; Richardson, Carrie; Mai, Ngoc; Humphrey, P. P. A.

doi:10.1038/sj.bjp.0705929

Cited by 112 publications

(103 citation statements)

References 40 publications

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“…17,41,46) The contractile 5-HT 2A and 5-HT 2B receptors identified in antral, corporal and fundic circular muscles may play a role in the in vivo contractile activities. The gastrokinetic effect of 5-HT 4 agonists has been demonstrated in rats.…”

Section: Discussionmentioning

confidence: 99%

“…However, the in vivo studies for examining gastric motility and gastric emptying using guinea pigs are limited. On the other hand, the rat is widely used as in vivo models to study gastric motility [17][18][19] and gastric emptying rate. [20][21][22] The stimulation of 5-HT 2 receptors increases gastric motility, 17) the blockade of 5-HT 3 receptors accelerates gastric emptying, 20) and the stimulation of 5-HT 4 receptors increases gastric motility 18) and accelerates gastric emptying.…”

mentioning

confidence: 99%

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Pharmacological Characterization of 5-Hydroxytryptamine-Receptor Subtypes in Circular Muscle from the Rat Stomach

Komada

Yano

2007

Biological & Pharmaceutical Bulletin

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It is generally accepted that gastric emptying is regulated by the coordination of the proximal and distal stomach motilities. 5-HT has proven to be an important mediator of gastrointestinal motility.1,2) The stimulation of 5-HT 1B/1D receptors induces gastric accommodation in humans 3) and dogs, 4) and delays gastric emptying in humans. 5,6) The blockade of 5-HT 3 receptors inhibits gastrointestinal motility in humans. 7) In addition, the stimulation of 5-HT 4 receptors elicits gastrointestinal contractile activity and increases the rate of gastric emptying in humans 8,9) and dogs. [10][11][12] With regard to gastric smooth muscle activity, it is generally accepted that the 5-HT 1B/1D and 5-HT 7 receptors are relaxant whereas the 5-HT 2 , 5-HT 3 and 5-HT 4 receptors are contractile. Although the gastric contractility of 5-HT has been reported in a variety of species and stomach regions, regional and functional differences of 5-HT-receptor subtypes have been fully investigated only in the guinea pig stomach. [13][14][15][16] In the guinea pig stomach, the fundus presents the relaxant 5-HT 1 receptors and the contractile 5-HT 2 and 5-HT 3 receptors, the corpus presents the relaxant 5-HT 1 receptors and the contractile 5-HT 3 and 5-HT 4 receptors, and the antrum presents the contractile 5-HT 2 , 5-HT 3 and 5-HT 4 receptors. However, the in vivo studies for examining gastric motility and gastric emptying using guinea pigs are limited. On the other hand, the rat is widely used as in vivo models to study gastric motility [17][18][19] and gastric emptying rate. [20][21][22] The stimulation of 5-HT 2 receptors increases gastric motility, 17) the blockade of 5-HT 3 receptors accelerates gastric emptying, 20) and the stimulation of 5-HT 4 receptors increases gastric motility 18) and accelerates gastric emptying. 20,21) In in vitro, pharmacological characterization of the contractile response to 5-HT in the rat stomach regions still remains unclear, except for the contractile 5-HT 2B receptors in longitudinal muscle strips of the fundus. [23][24][25] The present study was, therefore, designed to provide further information regarding functions of 5-HT receptor subtypes in circular muscle strips from the antrum, corpus and fundus of the rat stomach. MATERIALS AND METHODSChemicals Carbachol (CCh), atropine sulfate monohydrate and tetrodotoxin (TTX) were purchased from Wako Pure Chemicals (Osaka, Japan). 5-Hydroxytryptamine hydrochloride (5-HT), methysergide maleate, ketanserin tartrate and SB-269970 (selective 5-HT 7 receptor antagonist) were purchased from Sigma (St. Louis, MO, U.S.A.). WAY-100635 maleate (selective 5-HT 1A receptor antagonist), GR127935 hydrochloride (5-HT 1B/1D receptor antagonist) and cinanserin hydrochloride (selective 5-HT 2 receptor antagonist) were purchased from Tocris Cookson (Ellisville, MO, U.S.A.). RS-127445 (selective 5-HT 2B receptor antagonist), ondansetron (selective 5-HT 3 receptor antagonist) and SB-203186 (selective 5-HT 4 receptor antagonist) were synthesized at Pfizer Inc. All the drugs...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pharmacological Characterization of 5-Hydroxytryptamine-Receptor Subtypes in Circular Muscle from the Rat Stomach

Komada

Yano

2007

Biological & Pharmaceutical Bulletin

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“…Tegaserod has been shown to enhance gastric accommodation and normalize delayed gastric emptying [Thumshirn et al 2007;Beattie et al 2004]. The results of 2 large clinical trials yielded mixed results, but a meta-analysis demonstrated an improvement with tegaserod (NNT of 16) [Vakil et al 2008].…”

Section: Prokineticsmentioning

confidence: 99%

Review: Evaluation and management of dyspepsia

Harmon

Peura

2010

Therap Adv Gastroenterol

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Dyspepsia is a common clinical problem seen by both primary care physicians and gastroenterologists. Initial evaluation should focus on the identification and treatment of potential causes of symptoms such as gastroesophageal reflux disease (GERD), peptic ulcer disease, and medication side effects but also on recognizing those at risk for more serious conditions such as gastric cancer. This manuscript discusses the evaluation and management of dyspepsia including the role of proton-pump inhibitors, treatment of Helicobacter pylori, and endoscopy. Finally, treatment of refractory functional dyspepsia is addressed.

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“…Unlike tegaserod, velusetrag has no appreciable affinity for 5-HT 1D , 5-HT 2A , or 5-HT 2B receptors (Beattie et al, 2004;Smith et al, 2007). In contrast to cisapride, velusetrag has no significant affinity for the human ether-ago-go-related gene potassium channel (Smith et al, 2008).…”

Section: Velusetragmentioning

confidence: 99%

Core Aspects of Clinical Development and Trials in Chronic Idiopathic Constipation

Harris¹,

Daniëls²

2012

Constipation - Causes, Diagnosis and Treatment

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The 5‐HT₄ receptor agonist, tegaserod, is a potent 5‐HT_2B receptor antagonist in vitro and in vivo

Cited by 112 publications

References 40 publications

Pharmacological Characterization of 5-Hydroxytryptamine-Receptor Subtypes in Circular Muscle from the Rat Stomach

Pharmacological Characterization of 5-Hydroxytryptamine-Receptor Subtypes in Circular Muscle from the Rat Stomach

Review: Evaluation and management of dyspepsia

Core Aspects of Clinical Development and Trials in Chronic Idiopathic Constipation

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