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Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

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Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates these...
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5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
Regulation of Food Intake01:30

Regulation of Food Intake

Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists01:29

Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists

Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.
Phenothiazines, such as prochlorperazine...
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Tetrahydrocannabinol (THC) is a phytocannabinoid that primarily interacts with the CB1 receptor, a type of G protein-coupled receptor (GPCR) predominantly in and around the chemoreceptor trigger zone (CTZ) and emetic center. THC also blocks the serotonin receptor activity in the dorsal vagal complex (DVC) by inhibiting serotonin release. THC exerts its anti-emetic effects through these interactions, which are beneficial for patients undergoing chemotherapy.
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Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...

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Cisplatin-induced anorexia and ghrelin.

Tomohisa Hattori1, Koji Yakabi, Hiroshi Takeda

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Cisplatin chemotherapy causes nausea, vomiting, and appetite loss by affecting serotonin receptors. Targeting specific serotonin receptors and ghrelin pathways may prevent these side effects.

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Area of Science:

  • Oncology
  • Neuroscience
  • Gastroenterology

Background:

  • Cisplatin is a vital chemotherapy drug for various cancers.
  • Chemotherapy-induced nausea, vomiting, and anorexia significantly reduce patient quality of life and treatment adherence.
  • Current antiemetic strategies offer moderate relief but do not fully address anorexia.

Purpose of the Study:

  • To elucidate the mechanism of cisplatin-induced anorexia.
  • To identify specific serotonin (5-HT) receptor subtypes involved in chemotherapy-induced appetite loss.
  • To explore potential therapeutic targets for preventing and treating anorexia during cisplatin treatment.

Main Methods:

  • Review of existing literature on cisplatin's side effects and receptor pharmacology.
  • Analysis of the role of serotonin (5-HT) and its receptors in mediating nausea, vomiting, and anorexia.
  • Investigation of the impact of 5-HT receptor activation on ghrelin secretion.

Main Results:

  • Cisplatin administration releases large amounts of serotonin (5-HT), triggering nausea, vomiting, and anorexia.
  • Activation of 5-HT2b and 5-HT2c receptors is particularly implicated in cisplatin-induced anorexia.
  • These receptor activations lead to reduced secretion of ghrelin, an appetite-stimulating hormone.

Conclusions:

  • The mechanism of cisplatin-induced anorexia involves specific serotonin receptor subtypes (5-HT2b and 5-HT2c) and subsequent reduction in ghrelin.
  • Targeting these receptors and the ghrelin pathway holds promise for future clinical interventions.
  • Exogenous ghrelin, synthetic agonists, and rikkunshito are potential therapeutic agents for managing chemotherapy-induced anorexia.