Synthesis and pharmacological evaluation of benzamide derivatives as selective 5-HT4 receptor agonists

Sonda, Shuji; Kawahara, Toshio; Katayama, Ken-ichi; Sato, Noriko; Asano, Kiyoshi

doi:10.1016/j.bmc.2005.02.016

Cited by 19 publications

(12 citation statements)

References 19 publications

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“…Not only 5-HT 3 receptors but also 5-HT 4 receptors mediate colonic motility and fecal pellet output in response to endogenous or exogenous 5-HT in rodents (2,18,22,24,39,42,43). In mouse, rat, and human intestine, the peristaltic reflex is initiated by mucosal release of 5-HT and activation of 5-HT 4 receptors on CGRP sensory neurons, which is relayed to VIP/nitric oxide inhibitory motor neurons and to ACh/tachykinin excitatory motor neurons (17) Further studies are needed to address whether 5-HT 4 receptors are involved in mediating the stimulation of colonic motility in response to restraint stress in rats.…”

Section: Discussionmentioning

confidence: 99%

Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats

Tsukamoto

Ariga²,

Mantyh³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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(EC) cells of the epithelial cells release 5-HT into the lumen, as well as basolateral border. However, the physiological role of released 5-HT into the lumen is poorly understood. Concentrations of 5-HT in the colonic mucosa, colonic lumen, and feces were measured by HPLC in rats. To investigate whether intraluminal 5-HT accelerates colonic transit, 5-HT and 51 Cr were administered into the lumen of the proximal colon, and colonic transit was measured. To investigate whether 5-HT is released into the lumen, we used an ex vivo model of isolated vascularly and luminally perfused rat proximal colon. To investigate whether luminal 5-HT is involved in regulating stressinduced colonic motility, the distal colonic motility was recorded under the stress loading, and a 5-HT3 receptor antagonist (ondansetron, 10 Ϫ6 M, 0.5 ml) was administered intraluminally of the distal colon. Tissue content of 5-HT in the proximal colon (15.2 Ϯ 4.3 ng/mg wet tissue) was significantly higher than that in the distal colon (3.3 Ϯ 0.7 ng/mg wet tissue), while fecal content and luminal concentration of 5-HT was almost the same between the proximal and distal colon. Luminal administration of 5-HT (10 Ϫ6 -10 Ϫ5 M) significantly accelerated colonic transit. Elevation of intraluminal pressure by 10 cmH2O significantly increased the luminal concentration of 5-HT but not the vascular concentration of 5-HT. Stress-induced stimulation of the distal colonic motility was significantly attenuated by the luminal administration of ondansetron. These results suggest that luminally released 5-HT from EC cells plays an important role in regulating colonic motility in rats. enterochromaffin cells; distal colon; luminal pressure; restraint stress SEROTONIN (5-HT) IN THE GASTROINTESTINAL (GI) tract is involved in regulating GI motility. While 5-HT acts as a neurotransmitter of the enteric nervous system (15), the majority of 5-HT is stored in enterochromaffin (EC) cells of epithelial cells.EC cells have been considered to release 5-HT mainly into the blood vessels and/or intrinsic nerve terminal via a basolateral border (14). In contrast, others showed that 5-HT is also released into the intestinal lumen in response to vagal nerve stimulation (1,20), luminal acidification (25), and food intake (10). Immunoelectron microscopic study showed the anatomical evidence that 5-HT is released from EC cells in response to an increase of luminal pressure of the rat duodenum (12). However, the physiological role of released 5-HT into the GI lumen is poorly understood.In this study, we hypothesize that luminally released 5-HT from EC cells of the proximal colon is transferred distally with feces and stimulates motility of the distal colon, resulting in acceleration of colonic transit in rats. We also investigated the mechanism of luminal release of 5-HT of the rat proximal colon.There is accumulated evidence that a variety of stress stimulates colonic motility, colonic transit, and fecal pellet output (9,21,35,38,47). Stress-induced acceleration of colonic motor function...

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Section: Discussionmentioning

confidence: 99%

Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats

Tsukamoto

Ariga²,

Mantyh³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The 3 and 4-carboxy phenyl tropanylidenes provided little or no analgesic effects in the same testing paradigm most likely due to poor oral absorption or brain penetration and observed no instances of convulsions or deaths with these compounds. effects [12]. A Series of 4-amino-5-chloro-2-methoxy-N-(piperidin-4-yl-methyl) benzamides with a polar substituent group at the 1-position of the piperidine ring was evaluated for its effect on gastrointestinal motility.…”

Section: Analgesic Activitymentioning

confidence: 99%

“…In the oral route of administration, this compound enhanced gastric emptying and defecation in mice, and has a possibility as a prokinetic agent, which is effective on both the upper and lower gastrointestinal tract [13]. (Azaadamantanone was converted to a series of amino azacadamantane benzamides (Scheme 17a-d) were profiled for serotonin receptor activity.…”

Section: Analgesic Activitymentioning

confidence: 99%

Pharmacological Potential of Benzamide Analogues and their Uses in Medicinal Chemistry

Asif¹

2016

Mod Chem Appl

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Benzamide derivatives possess different kinds of pharmacological activities like antimicrobial, analgesic, antiinflammatory, anticancer, cardiovascular, and other biological activities. Due to these biologically significances, scientists have interesting to develop various new benzamide derivatives. There is still need to improve the already used benzamide derivatives and search for the new and more effective benzamide derivatives. This review exhibited various pharmacophoric activities of benzamides analogues which are biologically importance.

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“…The inhibitory activity of these drugs on B-Raf kinase [11,12] revealed that the substituted benzene sulphonamido group is important for inhibitory activity. On the other hand the molecular entities possessing Heterocyclic/ non heterocyclic and substituted/unsubstituted benzamides have been well investigated to possess antimicrobial [13][14][15][16][17][18][19][20], analgesic, anti-inflammatory [21,22], anticonvulsant [23][24][25][26][27][28], anticancer [29][30][31][32][33], and other biological activities [34][35][36][37][38][39][40][41] and imidazopyridazines being structural analogues of purines were also reported to be promising scaffolds exhibiting a wide range of biological activities [42][43][44][45][46]. In view of these reports, our interest moved to develop new benzamido substituted scaffolds which are isosteric analogs of sulphonamido substituted marketed drugs as possible B-Raf Kinase inhibitors and are expected to acquire different selectivities and novelties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, in silico and in vitro anti-proliferative studies of some novel benzamido substituted imidazo[1,2-b]pyridazin-2-ones

Sruthi¹,

Sumakanth²

2017

Ankara Üniversitesi Eczacılık Fakültesi Dergisi

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Synthesis and pharmacological evaluation of benzamide derivatives as selective 5-HT4 receptor agonists

Cited by 19 publications

References 19 publications

Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats

Luminally released serotonin stimulates colonic motility and accelerates colonic transit in rats

Pharmacological Potential of Benzamide Analogues and their Uses in Medicinal Chemistry

Synthesis, in silico and in vitro anti-proliferative studies of some novel benzamido substituted imidazo[1,2-b]pyridazin-2-ones

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