Tradipitant

Overview

Tradipitant is a neurokinin-1 receptor (NK-1R) antagonist currently in clinical development for atopic dermatitis, gastroparesis and motion sickness. Tradipitant was licensed by Vanda from Eli Lilly and Company (Lilly) in 2012.


Neurokinin-1 Receptor and Substance P

The NK-1R is expressed in several tissues of the body, mainly associated with the nervous system. Substance P (SP) and NK-1R are thought to regulate neurogenic inflammation and the pain perception pathway through the central nervous system. Other tissues, including endothelial cells and immune cells, also express NK-1R and could be considered to be targets for NK-1R antagonists1.

The activation of NK-1R by the natural ligand SP is thought to be involved in the perception of pain, behavioral stress response, cravings and nausea and vomiting signaling1,2,3. Abnormal over-expression or over-activation of the NK-1R, either in the central nervous system or peripherally, could result in pathological conditions such as pruritus, nausea/vomiting, substance dependence and anxiety1,2,3,4.

A NK-1R antagonist may possess the ability to reduce the over-stimulation of the NK-1R, and as a result address the underlying pathophysiology of the symptoms in these conditions. NK-1R antagonists are currently approved for postoperative and chemotherapy induced nausea.

References

  1. Almeida TA, Rojo J, Nieto PM, Pinto FM, Hernandez M, et al. Tachykinins and tachykinin receptors: structure and activity relationships. Current Medicinal Chemistry. 2004;11:2045-2081.
  2. George DT, Gilman J, Hersh J, Thorsell A, Herion D, Geyer C, Peng X, Keilbasa W, Rawlings R, Brandt JE, Gehlert DR, Tauscher JT, Hunt SP, Hommer D, Heilig M. Neurokinin 1 receptor antagonism as a possible therapy for alcoholism. Science. 2008; 319(5869):1536-9
  3. Hargreaves R, Ferreira JC, Hughes D, Brands J, Hale J, Mattson B, Mill S. Development of aprepitant, the first neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Annals of the New York Academy of Sciences. 2011; 1222:40-48.
  4. Stander S, Weisshaar E, Luger A. Neurophysiological and neurochemical basis of modern pruritus treatment. Experimental Dermatology. 2007;17:161-69.
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