Info Neurokinin Receptor Modulators

Neurokinin (NK) receptors NK1, NK2, and NK3 for tachykinin peptides are distributed widely in the CNS and on sensory enteric neurons. Targeting NK receptors to modulate sensorimotor function in the gut is therefore a potential treatment modality for patients with IBS.

NK1 are preferential receptors for substance P in myenteric neurons and afferent pathways and are expressed on neuronal and non-neuronal cells involved in gut motility. Blockade of NK1 in the gut inhibits peristalsis, and blockade of NK1 in the spinal cord attenuates abdominal contractions evoked by colorectal distension.194 The NK1 antagonist aprepitant 5 relieves chemotherapy-induced emesis, an effect likely related to vagal afferent inhibition, but this agent has not been tested in patients with IBS. In a preliminary study of patients with IBS, treatment with another NK1 antagonist, ezlopitant 6, reduced anger related to rectal balloon distension. In addition, blockade of substance P may reduce bowel inflammation and thus exert analgesic effects.192

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