NK1 receptor antagonist

Neurokinin 1 (NK1) antagonists (-pitants) are a novel class of medications that possesses unique antidepressant,[1][2] anxiolytic,[3] and antiemetic properties. NK-1 antagonists boost the efficacy of 5-HT3 antagonists to prevent nausea and vomiting. The discovery of neurokinin 1 (NK1) receptor antagonists was a turning point in the prevention of nausea and vomiting associated with cancer chemotherapy.[4]

An example of a drug in this class is aprepitant. Chemotherapy-induced emesis appears to consist of acute and delayed phases. So far, the acute phase emesis responds to 5-HT3 antagonists while the delayed phase remains difficult to control. The discovery and development of NK1 receptor antagonists have elicited antiemetic effect in both acute and especially in delayed phases of emesis.[5] Casopitant, netupitant and rolapitant are some newer additions in this group. Rolapitant has a significantly longer half-life of 160 hours and was approved by the US FDA in 2015.

The first registered clinical use of NK1 receptor antagonists was the treatment of emesis, associated with cancer chemotherapy.[6]

  1. ^ Cite error: The named reference pmid9733503 was invoked but never defined (see the help page).
  2. ^ Varty GB, Cohen-Williams ME, Hunter JC (February 2003). "The antidepressant-like effects of neurokinin NK1 receptor antagonists in a gerbil tail suspension test". Behav Pharmacol. 14 (1): 87–95. doi:10.1097/00008877-200302000-00009. PMID 12576885. S2CID 12218489.
  3. ^ Varty GB, Cohen-Williams ME, Morgan CA, et al. (2002), "The gerbil elevated plus-maze II: anxiolytic-like effects of selective neurokinin NK1 receptor antagonists", Neuropsychopharmacology, 27 (3): 371–9, doi:10.1016/S0893-133X(02)00313-5, PMID 12225694.
  4. ^ Hesketh, P. J. (1994), "New treatment options for chemotherapy-induced nausea and vomiting", Supportive Care in Cancer, 12 (8): 550–554, doi:10.1007/s00520-004-0651-0, PMID 15232725, S2CID 6081469, archived from the original on 2013-01-29
  5. ^ Watanabe, Y.; Asai, H.; Ishii, T.; Kiuchi, S.; Okamoto, M.; Taniguchi, H.; Nagasaki, M.; Saito, A. (January 2008), "Pharmacological characterization of T-2328, 2-fluoro-4 '-methoxy-3 '-((((2S,3S)-2-phenyl-3-piperidinyl)amino)methyll)(1,1 '-biphenyl)-4-carbonitrile dihydrochloride, as a brain-penetrating antagonist of tachykinin NK1 receptor", Journal of Pharmacological Sciences, 106 (1): 121–127, doi:10.1254/jphs.FP0071400, PMID 18187929
  6. ^ Brain, S. D.; Cox, H. M. (2006), "Neuropeptides and their receptors: innovative science providing novel therapeutic targets", British Journal of Pharmacology, 147 (S1): S202–S211, doi:10.1038/sj.bjp.0706461, PMC 1760747, PMID 16402106