Defensive and pathological functions of the gastrointestinal NK3 receptor

Sanger, Gareth J.; Tuladhar, B. R.; Buéno, Lionel; Furness, John B.

doi:10.1016/j.vph.2005.08.026

Cited by 7 publications

(7 citation statements)

References 48 publications

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“…The other two studies performed in IBS patients (n = 618 for the first study and n = 732 for the second) confirmed the inactivity of talnetant on IBS symptoms [134]. These were two double-blind, placebo-controlled, parallel-group multicenter studies conducted in patients with at least a 6-month history of IBS meeting Roma II criteria [137] and having an average of mild to moderate abdominal pain during a 2-week baseline period.The initial study evaluated three doses of talnetant (3, 25 and 100 mg q.i.d.)…”

Section: Clinical Studies In Ibsmentioning

confidence: 82%

“…Tachykinins are important neurotransmitters in the modulation of visceral afferent information and both peripheral and supraspinal tachykinin NK3 receptors have been demonstrated preclinically to mediate neurotransmission involved in stress and pain, the main symptoms of IBS [134]. In view of the above, three studies have been performed in humans (one in healthy volunteers [135], the other two in IBS patients [136]), in order to test the potential efficacy of talnetant in modulating visceral sensitivity.…”

Section: Clinical Studies In Ibsmentioning

confidence: 99%

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Tachykinin receptor antagonists in clinical trials

Quartara

Altamura

Evangelista

et al. 2009

Expert Opinion on Investigational Drugs

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Tachykinins (TKs) are small peptides widely distributed in the central and peripheral nervous systems where they act as neurotransmitters. Potent and selective TKs antagonists have been developed in the last 20 years and many efforts have been made to prove their efficacy in the treatment of various diseases. Herein the most prominent results in the clinical development are reported and discussed. For aprepitant, the only compound of this class to have been launched to date, results of clinical studies and postmarketing cost-effectiveness data for the treatment of chemotherapy-induced emesis are discussed. The field is still well active, as currently proof-of-concept studies for indications initially missed (i.e., depression) are ongoing and new targets are under investigation.

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Section: Clinical Studies In Ibsmentioning

confidence: 82%

Section: Clinical Studies In Ibsmentioning

confidence: 99%

Tachykinin receptor antagonists in clinical trials

Quartara

Altamura

Evangelista

et al. 2009

Expert Opinion on Investigational Drugs

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“…Both NKB and NK 3 receptors, which bind NKB with the highest affinity, are predominantly expressed in the CNS, where NKB exerts neural activation. There is some evidence that NK 3 receptors also exist on the periphery, mainly in the joints , airways and gastrointestinal tract .…”

Section: Pro‐inflammatory Neuropeptidesmentioning

confidence: 99%

Neuropeptide receptors as potential drug targets in the treatment of inflammatory conditions

Pintér

Pozsgai

Hajna

et al. 2013

Brit J Clinical Pharma

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Cross-talk between the nervous, endocrine and immune systems exists via regulator molecules, such as neuropeptides, hormones and cytokines. A number of neuropeptides have been implicated in the genesis of inflammation, such as tachykinins and calcitonin gene-related peptide. Development of their receptor antagonists could be a promising approach to anti-inflammatory pharmacotherapy. Anti-inflammatory neuropeptides, such as vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, a-melanocyte-stimulating hormone, urocortin, adrenomedullin, somatostatin, cortistatin, ghrelin, galanin and opioid peptides, are also released and act on their own receptors on the neurons as well as on different inflammatory and immune cells. The aim of the present review is to summarize the most prominent data of preclinical animal studies concerning the main pharmacological effects of ligands acting on the neuropeptide receptors. Promising therapeutic impacts of these compounds as potential candidates for the development of novel types of anti-inflammatory drugs are also discussed.

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“…In the myenteric ganglia, NK 3 receptors are found on the (1) IPANs, (2) excitatory motor neurons and ascending motor neurons, (3) inhibitory motor neurons, (4) descending interneurons, and (5) secretomotor neurons. In the submucosal ganglia, NK 3 receptors are present on (1) secremotor/vasodilator neurons, (2) secremotor neurons, and (3) cell bodies in myenteric and submucous plexi of the small and large intestines. , In terms of function, both NK 1 and NK 3 receptors are involved in neuro−neuronal transmission in the enteric nervous system. Tachykinins have roles in the generation of slow EPSPs that are mediated by NK 1 and NK 3 receptors in the IPANs, and in both ascending and descending pathways affecting motility. , Indeed, transmission at the first synapse between the IPAN and interneurons following the stimulation of mucosal reflexes within descending motility-controlling pathways involves tachykinins via the activation of NK 3 receptors, whereas transmission from IPANs to the inhibitory muscle motor neurons involves NK 1 receptors.…”

Section: Substance P: Synthesis Storage Release Degradation and Recep...mentioning

confidence: 99%