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

Rupniak NM, Kramer MS
Merck Sharp & Dohme Neuroscience Research Centre,
Harlow, Essex, UK.
Trends Pharmacol Sci 1999 Dec;20(12):485-90


The development of small-molecule antagonists of the substance P (SP)-preferring tachykinin NK1 receptor during the past decade represents an important opportunity to exploit these molecules as novel therapeutic agents. On the basis of its anatomical localization and function, SP has been implicated in diverse pathophysiologies; of these, diseases of the CNS have been examined in the greatest detail. Although SP is best known as a pain neurotransmitter, it also controls vomiting and various behavioural, neurochemical and cardiovascular responses to stress. Recent clinical trials have confirmed the efficacy of NK1 receptor antagonists to alleviate depression and emesis but, surprisingly, not pain. Thus, multiple clinical trials, targeted to appropriate patient populations, are necessary to define the therapeutic potential of novel neurotransmitter ligands.
Substance P
21st Century
Sigma ligands
NMDA antagonists
Substance P: review
New antidepressants
Substance P and opiates
Neurokinins/Substance P
New Substance P antagonists
Neurokinin receptor-1 antagonists
Neurokinin receptor-2 antagonists
Happy, relaxed mice lack tac1 gene
Substance P receptors (NK1) and aprepitant
Substance P antagonists as antidepressants
Substance P: effects on sleep, mood, and neuroendocrine function

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