The κ agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome

Delvaux, Michel; Louvel, Dominique; Lagier, E; Scherrer, Bruno; Abitbol, Jean‐Louis; Frexinos, Jacques

doi:10.1016/s0016-5085(99)70226-x

Cited by 143 publications

(108 citation statements)

References 23 publications

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“…Experimental studies exhibited that fedotozine and asimadoline are among agonists of κ-opioid receptors which can significantly reduce pain sensation. 78,79 In a clinical trial on patients with IBS, fedotozine significantly decreased volume or pressure stimuli perception. Likewise, in another clinical study, asimadoline alleviated functional dyspepsia symptoms, particularly hyperalgesia.…”

Section: -77mentioning

confidence: 99%

“…Likewise, in another clinical study, asimadoline alleviated functional dyspepsia symptoms, particularly hyperalgesia. 79,80 It has been found that activation of µ-opioid receptors by exogenous opioids can reduce bowel transition. Eluxadoline, a µ-opioid receptor agonist and d-opioid receptor antagonist, showed a significant elevation in pain threshold in IBS-D patients.…”

Section: -77mentioning

confidence: 99%

See 1 more Smart Citation

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

Farzaei

Bahramsoltani

Abdollahi

et al. 2016

J Neurogastroenterol Motil

146

122

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Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. Molecular mediators and receptors participating in pain perception and visceroperception include histamine-1 receptors, serotonin (5-hydrodytryptamine) receptors, transient receptor potential vanilloid type I, tachykinins ligands, opioid receptors, voltage-gated channels, tyrosine receptor kinase receptors, protease-activated receptors, adrenergic system ligands, cannabinoid receptors, sex hormones, and glutamate receptors which are discussed in the current review. Moreover, several plant-derived natural compounds with potential to alleviate VH in IBS have been highlighted. VH has an important role in the pathology and severity of complications in IBS. Therefore, managing VH can remarkably modulate the symptoms of IBS. More preclinical and clinical investigations are needed to provide efficacious and targeted medicines for the management of VH. (J Neurogastroenterol Motil 2016;22:558-574)

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Section: -77mentioning

confidence: 99%

Section: -77mentioning

confidence: 99%

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

Farzaei

Bahramsoltani

Abdollahi

et al. 2016

J Neurogastroenterol Motil

146

122

View full text Add to dashboard Cite

show abstract

“…One hypothesis is that this peripherally located receptor is the κ receptor, since there is some evidence that oxycodone has a partial effect at the κ opioid receptor [24,28] . In contrast to other opioid receptor types, for which central effects dominate, the peripheral κ receptor may also be important for visceral analgesia [3,29,30] . Staahl et al [17] have confirmed that morphine and oxycodone have somewhat different PK-PD relationships in attenuation of visceral pain and, therefore, most likely act at receptors situated in different physiological compartments.…”

Section: Opioidsmentioning

confidence: 99%

“…An experimental pain model activates different modalities and can be used to investigate the mechanism of action of different analgesics in detail. In combination with pharmacokinetic studies and objective assessment such as electroencephalography, new information re-sants and anticonvulsants) [3][4][5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Translational pain research: Evaluating analgesic effect in experimental visceral pain models

Olesen¹,

Christrup²,

Upton³

2009

WJG

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“…Fentanyl (5 mL kg )1 ) was administered subcutaneously about 1 min after the third inflation. The 12 distensions were divided into two groups: before (distensions 1-3) and after drug administration (distensions [4][5][6][7][8][9][10][11][12]. The average VMR of distensions 1-3 was set to 100% (for calculations, see Materials and methods).…”

Section: Involvement Of Opioid Receptors In the Attenuation Of The Vmmentioning

confidence: 99%

Involvement of κ‐opioid receptors in visceral nociception in mice

Larsson

Bayati

Lindström

et al. 2008

Neurogastroenterology Motil

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It has been shown that the behavioural responses to chemically evoked visceral nociception are increased in transgenic mice lacking the j-opioid receptor (KOR). The aim of the present study was to evaluate the contribution of KOR in mechanically evoked visceral pain by performing colorectal distension (CRD) and monitoring the subsequent visceromotor response (VMR) in control mice (KOR +/+ ) and in mice lacking KOR (KOR )/) ). Pseudo-affective visceral pain responses were evoked in conscious mice using increasing (10-80 mmHg) and repeated (12 · 55 mmHg) phasic CRD paradigms. The resulting VMR was determined by monitoring the electromyographic activity of the abdominal muscle. The increasing and repeated CRD paradigms, respectively, evoked similar responses in both KOR +/+ and KOR )/) mice. The selective KOR-agonists U-69593 (5 and 25 mg kg )1 , s.c.) and asimadoline (25 mg kg )1 , s.c.) significantly decreased the VMR in KOR +/+ mice, while having no effect in KOR )/) mice. In contrast, the selective l-opioid receptor agonist fentanyl significantly reduced the VMR in both types of mice and appeared more efficacious in KOR )/) mice. The opioid receptor antagonist naloxone (0.3-30 mg kg )1 s.c.) did not affect the response to CRD in C57BL/6 mice at any dose tested. In conclusion, the data confirm that the KOR agonists used in this study inhibit the VMR to CRD in mice by acting via KOR receptors. In addition, the data suggest that the endogenous opioid system is not likely to modulate the VMR to mechanically evoked visceral pain in mice.

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The κ agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome

Cited by 143 publications

References 23 publications

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments

Translational pain research: Evaluating analgesic effect in experimental visceral pain models

Involvement of κ‐opioid receptors in visceral nociception in mice

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