Pharmacological implications of tachykinins:
Tachykinins have got some important implications as pharmacological
agents since the approval of their first agent Aprepitant by FDA in 2003
which is now widely used CINV.53
Various other congeners of Aprepitant were also approved subsequently.
Casopitant, Netupitant and Rolapitant were approved later
on.54, 55, 56Apart from vomiting Aprepitant was also
tried as an agent for Depression.57 This compound has
also shown antiproliferative properties in tumoral cell lines of glioma,
neuroblastoma, retinoblastoma, pancreas, larynx, colon, and gastric
carcinoma.58, 59, 60, 61Experimental studies in the
rabbit colon suggest that NK2 receptors antagonist MEN 11420
(Nepadutant) may also dose-dependently modulate colonic
transit.62The selective inhibition of peripheral NK3
receptors by SB-235375 (Talnetant) reduced the nociceptive response to
colorectal distension in the rat model.63, 64According
to these studies, specific NK3 receptor antagonists exhibit potential as
analgesic agents for visceral pain in IBS patients. Recombinant NEP and
NK1 receptor antagonist SR140333 prevented the exacerbated inflammation
in NEP knockout mice.65, 66, 67 Selective tachykinin
receptors antagonists tested on guinea pigs have been shown to inhibit
the late allergic and airway hyperresponsiveness and reduce eosinophilic
infiltration and vascular
permeability.68,69,70 However, all these studies were
at a very preliminary stage and little of therapeutic benefit could be
inferred for humans. Some of the important clinical indications for
which tachykinin antagonists are tried are listed in the table
Table 2