Discovery of the anti-depressant and anti-emetic efficacy of substance P receptor (NK1) antagonists

The development of small-molecule antagonists of the substance P (SP)-prefe rring tachykinin NK1 receptor during the past decade represents an importan t opportunity to exploit these molecules as novel therapeutic agents. On th e basis of its anatomical localization and function, SP has been implicated in diverse pathophysiologies; of these, diseases of the CNS have been exam ined in the greatest detail. Although SP is best known as a pain neurotrans mitter, it also controls vomiting and various behavioural, neurochemical an d cardiovascular responses to stress. Recent clinical trials have confirmed the efficacy of NK1 receptor antagonists to alleviate depression and emesi s hut, surprisingly, not pain. Thus, multiple clinical trials, targeted to appropriate patient populations, are necessary to define the therapeutic po tential of novel neurotransmitter ligands.