Tachykinins and neuropsychiatric disorders

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• Classical tachykinins (substance P, neurokinin A, neurokinin B) function as neurotransmitters and neuromodulators, primarily in the nervous system.
• These tachykinins bind to their preferred receptors: NK1, NK2, and NK3 receptors.
• Substance P's role in nociception was initially supported by its presence in pain pathways, but NK1 antagonists proved ineffective for pain relief.

Purpose of the Study:

• To review the evolving understanding and therapeutic applications of tachykinin receptor antagonists.
• To explore the potential of NK1, NK2, and NK3 receptor antagonists in various clinical conditions.
• To discuss the implications of newly discovered tachykinins on the use of NK1 receptor antagonists.

Main Methods:

• Review of existing literature on tachykinins and their receptor antagonists.
• Analysis of clinical trial outcomes for NK1, NK2, and NK3 receptor antagonists.
• Consideration of novel tachykinin families and their impact on therapeutic strategies.

Main Results:

• NK1 receptor antagonists, initially explored for pain, showed antidepressant activity but faced trial suspensions.
• Aprepitant (an NK1 antagonist) is approved for chemotherapy-induced emesis.
• NK3 receptor antagonists demonstrated efficacy in schizophrenia treatment.
• New tachykinins (hemokinins, endokinins) acting on NK1 receptors affect immune cells, impacting NK1 antagonist use.

Conclusions:

• The therapeutic utility of NK1 receptor antagonists extends beyond pain, notably in antiemesis and potentially in depression.
• NK3 receptor antagonists show promise for treating schizophrenia.
• The discovery of hemokinins and endokinins necessitates specific strategies for using NK1 antagonists in neuropsychiatric disorders.