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