Question

A man complains of dry mouth after radiation therapy for throat cancer, and he is treated with cevimeline. Which mechanism produces the therapeutic effect of this drug? (A) activation of muscarinic \(M_2\) receptors (B) increased formation of \(\mathrm{IP}_3\) (C) increased cAMP levels (D) increased cGMP levels (E) increased potassium efflux

Short answer

The therapeutic effect of cevimeline is produced by increased formation of \( \mathrm{IP}_3 \). (Option B)

Step-by-step solution

Identify the Drug's Class and Action

Cevimeline is a medication that is used to treat dry mouth caused by radiation therapy or Sjögren's syndrome. It is classified as a cholinergic agonist, specifically targeting muscarinic receptors.

Determine the Affected Receptors

Cevimeline primarily acts on muscarinic receptors, particularly the \( M_3 \) subtype, which is involved in stimulating exocrine gland secretion, such as saliva production, thus alleviating dry mouth.

Analyze Relevant Intracellular Pathways

The activation of \( M_3 \) muscarinic receptors leads to the activation of phospholipase C, which increases the formation of inositol trisphosphate (\( \mathrm{IP}_3 \)). This molecule then causes the release of calcium from the endoplasmic reticulum, promoting secretion.

Associate Mechanism with Given Options

Among the options given, \( \mathrm{IP}_3 \) production corresponds to the mechanism by which cevimeline treats dry mouth by increasing saliva secretion through \( M_3 \) receptor activation. Thus, the correct answer is related to increased \( \mathrm{IP}_3 \) formation.

Key concepts

Cevimeline Mechanism of Action

Cevimeline is a medication known for its notable effect in alleviating symptoms of dry mouth, especially after radiation therapy or in cases of Sjögren's syndrome. It functions as a cholinergic agonist, meaning it mimics the action of the neurotransmitter acetylcholine. This helps to stimulate certain receptors in the body. Cevimeline primarily targets the muscarinic receptors, and more specifically, the \( M_3 \) subtype. By binding to and activating these receptors, it enhances the natural production of saliva, providing relief to patients experiencing a dry mouth. This mechanism is crucial as it directly counteracts the reduced saliva production seen in these medical conditions.

Muscarinic Receptors

Muscarinic receptors are a type of receptor found in the body that respond to the neurotransmitter acetylcholine. These are distinct from nicotinic receptors, another type of acetylcholine receptor. Muscarinic receptors are located in various parts of the body, influencing numerous physiological functions. There are five known subtypes, labeled \( M_1 \) to \( M_5 \).

• \( M_1 \), \( M_3 \), and \( M_5 \) are generally associated with the activation of phospholipase C and subsequent cellular responses.
• \( M_2 \) and \( M_4 \) are linked with the inhibition of adenylate cyclase, affecting cellular metabolism.

The \( M_3 \) receptors are particularly important in glandular function, such as saliva secretion, which is why they are targeted by drugs like cevimeline for their therapeutic effects in treating dry mouth.

Radiation Therapy Side Effects

Radiation therapy, although effective in treating cancer, often comes with a range of side effects due to its impact on healthy tissues. One common side effect in head and neck cancer treatments is xerostomia, or dry mouth. This occurs because the radiation can damage the salivary glands, reducing saliva production.
A lack of saliva can have multiple impacts, including:

• Difficulty swallowing
• Increased risk of dental decay
• Mouth infections
• Compromised taste

Medications like cevimeline can be an effective way to manage these symptoms by stimulating the remaining functional salivary gland tissue to produce more saliva, thus improving the patient's quality of life during and after cancer treatment.

Cholinergic Agonists

Cholinergic agonists are a class of drugs that mimic the action of acetylcholine, a neurotransmitter involved in many functions in the body. These drugs bind to acetylcholine receptors, both muscarinic and nicotinic, to promote physiological responses.
In the context of cevimeline, a muscarinic agonist, the drug specifically targets the \( M_3 \) muscarinic receptors, found in exocrine glands. This specificity is beneficial in treating conditions like dry mouth because it stimulates saliva production without significantly affecting other body systems.
Cholinergic agonists are used in various medical treatments, depending on their receptor specificity and the responses they elicit in targeted tissues.

Intracellular Signaling Pathways

The activation of \( M_3 \) muscarinic receptors by cevimeline or other agonists leads to a cascade of intracellular events. Once activated, these receptors stimulate the enzyme phospholipase C, resulting in the production of inositol trisphosphate (\( \mathrm{IP}_3 \)).
\( \mathrm{IP}_3 \) then plays a critical role in calcium mobilization within the cell. It binds to receptors on the endoplasmic reticulum, triggering the release of calcium ions into the cytosol.
This increase in intracellular calcium levels causes salivary glands to secrete more fluid, effectively increasing saliva production. Understanding these pathways is essential in pharmacology, as it illustrates how drugs can leverage existing cellular mechanisms to produce therapeutic effects.