From the Guidelines
Substance P causes nausea by binding to neurokinin-1 (NK1) receptors in the brain's chemoreceptor trigger zone and vomiting center, triggering a cascade of signals that stimulate the vomiting reflex. This mechanism is supported by a study published in the Journal of the National Comprehensive Cancer Network, which found that aprepitant, an NK-1 receptor antagonist, is effective in preventing nausea and vomiting in patients receiving highly emetogenic chemotherapy 1. The study showed that aprepitant selectively blocks the binding of substance P at the NK-1 receptor in the central nervous system, providing a different and complementary mechanism of action to other antiemetics.
Some key points to consider:
- Substance P is released during various conditions, including inflammation, pain, and in response to certain toxins or medications.
- NK1 receptor antagonists like aprepitant are effective antiemetic medications that work by blocking substance P from binding to NK1 receptors.
- The mechanism of substance P-induced nausea is complex and involves interactions with other neurotransmitter systems, including serotonin and dopamine pathways.
- Aprepitant has been shown to be effective in preventing both acute and delayed emesis in patients receiving highly emetogenic chemotherapy, with a significant benefit in improving complete response rates compared to standard antiemetic regimens 1.
The binding of substance P to NK1 receptors is a critical step in the nausea response, and blocking this interaction with NK1 receptor antagonists like aprepitant is a effective strategy for preventing nausea and vomiting, particularly in the context of chemotherapy-induced nausea and vomiting 1.
From the Research
Substance P and Nausea
- Substance P (SP) is a neuropeptide that binds to the neurokinin 1 receptor (NK-1R) and is involved in various biological processes, including emesis 2, 3, 4, 5, 6.
- The NK-1R is found in brain regions involved in the vomiting reflex, such as the nucleus tractus solitarius and the area postrema 2, 6.
- The binding of SP to the NK-1R contributes to the regulation of emesis, and antagonists of this receptor have been developed for the treatment of chemotherapy-induced nausea and vomiting (CINV) 2, 3, 5.
- The mechanism of emesis is complex and involves multiple neurotransmitters and receptors, including substance P and the NK-1R 6.
Role of Substance P in Emesis
- Substance P is released in response to stressful stimuli and binds to the NK-1R, leading to the activation of neurons involved in the emetic response 4, 6.
- The NK-1R is internalized and recycled to the plasma membrane after binding to substance P, allowing for repeated activation of the receptor 4.
- The role of substance P and the NK-1R in emesis has led to the development of NK-1R antagonists, such as aprepitant, for the treatment of CINV 2, 3, 5.
Clinical Applications
- NK-1R antagonists have been shown to be effective in the treatment of CINV and postoperative nausea and vomiting 2, 3, 5.
- The use of NK-1R antagonists for the treatment of other conditions, such as depression and anxiety, is being explored 4, 5.
- Further research is needed to fully understand the role of substance P and the NK-1R in emesis and to develop effective treatments for nausea and vomiting 6.