Substance P antagonists:
novel agents in the treatment of depression

Argyropoulos SV, Nutt DJ
Psychopharmacology Unit,
School of Medical Sciences,
University Walk, Bristol BS8 1TD, UK.
Expert Opin Investig Drugs 2000 Aug; 9(8):1871-1875


The field of neuropeptides has been expanding very rapidly in recent years. Apart from understanding their physiology and elucidating their functional role as putative neurotransmitters, research has focused on producing drugs that may treat a variety of illnesses in a novel way. Substance P antagonists occupy a central role in this area of intensive scientific activity. Substance P (SP), an undecapeptide, is abundant both in the periphery and in the CNS, where it is usually co-localised with one of the classical neurotransmitters, most commonly serotonin (5-HT). A role for SP is proposed in the regulation of pain, asthma, psoriasis, inflammatory bowel disease and, in the CNS, emesis, migraine, schizophrenia, depression and anxiety. A recently published positive study of MK 869, in depression, a novel SP antagonist has generated excitement amongst psychopharmacologists. It is the first time that a drug, not directly related to monoamine transmitters, has showed efficacy in depression. Although MK 869 has been suspended from further development, a host of other compounds, with similar action and better pharmacological profile, are currently under development. In this review, the pharmacology of central SP and its receptors are discussed, together with the exploration of the prospects and implications for future treatments of depression.
Substance P
21st Century
New antidepressants
Substance P antagonists
Neurokinins/substance P
Old and new antidepressants
New Substance P antagonists
Nitric oxide synthase inhibitors
Neurokinin receptor-1 antagonists
Neurokinin receptor-2 antagonists
Happy, relaxed mice lack tac1 gene
Substance P receptors (NK1) and aprepitant
Substance P: effects on sleep, mood, and neuroendocrine function

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