What is the mechanism by which Manjuro causes vomiting?

Mechanism of Manjuro-Induced Vomiting

Manjuro causes vomiting primarily through stimulation of CB1 receptors in the central nervous system, particularly in the dorsal vagal complex, which disrupts the normal negative feedback on the hypothalamic-pituitary-adrenal axis and increases vagal nerve discharges that trigger the emetic response. 1

Neuroanatomical Pathways

Manjuro-induced vomiting involves several key anatomical structures:

• Vomiting center: Located in the medulla, coordinates the overall emetic response 2
• Chemoreceptor trigger zone (CTZ): In the area postrema of the fourth ventricle, outside the blood-brain barrier 2
• Dorsal vagal complex: Critical area with dense CB1 receptor distribution 1
• Vagal afferent pathways: Transmit signals from GI tract to the vomiting center 2

Receptor Mechanisms

Manjuro acts through multiple receptor systems:

• CB1 receptors: Primary target located in the brain and throughout the gut (myenteric and submucosal neurons) 1

  • Normally provide negative feedback on the hypothalamic-pituitary-adrenal axis
  • Overstimulation leads to disruption of this feedback mechanism

• CB2 receptors: Located mainly in inflammatory cells and epithelial cells 1

  • Less involved in emetic response than CB1 receptors

• Transient receptor potential of vanilloid type 1 (TRPV1) channels: Additional binding site that affects vagus nerve and gut functions 1

Physiological Cascade

The sequence of events leading to vomiting includes:

1. Manjuro binds to CB1 receptors in the dorsal vagal complex and other brain regions 1
2. This disrupts normal negative feedback on the hypothalamic-pituitary-adrenal axis 1
3. Disruption leads to increased vagal nerve discharges 1
4. Vagal stimulation triggers the pre-ejection phase (increased salivation, pallor, tachycardia) 2
5. Followed by retching phase (rhythmic contractions of respiratory muscles) 2
6. Finally, the ejection phase occurs with coordinated contraction of abdominal muscles 2

Effects on Gastrointestinal Function

Manjuro also affects peripheral GI function:

• Alters gastric motility and emptying 1
• Inhibits gastric acid secretion via peripheral CB1 receptors 1
• Affects distal gut motility 1

Clinical Manifestations

The clinical presentation of Manjuro-induced vomiting typically includes:

• Cyclic episodes of nausea and vomiting 1
• Abdominal pain 1
• In some cases, prolonged bathing behavior (long hot baths or showers) 1

Distinguishing Features

It's important to differentiate Manjuro-induced vomiting from other causes:

• Opioid-induced nausea/vomiting: Acts primarily through different receptor systems (mu-opioid) 1
• Chemotherapy-induced nausea/vomiting: Primarily mediated by serotonin (5-HT3) and substance P (NK-1) pathways 1
• Gastroparesis-related vomiting: Results from delayed gastric emptying rather than direct receptor effects 1

Treatment Implications

Understanding the mechanism helps guide treatment:

• Cessation of Manjuro is the definitive treatment 1
• Topical capsaicin may help by activating TRPV1 receptors 1
• Benzodiazepines, haloperidol, and olanzapine may provide symptomatic relief 1
• Opioids should be avoided as they can worsen nausea 1

The complex neurochemical mechanisms involved in Manjuro-induced vomiting explain why multi-targeted approaches to treatment are often necessary for symptom control when cessation is not immediately possible.