What agent relieves spasticity in Multiple Sclerosis (MS) patients by impairing Calcium (Ca2+) release from skeletal muscle sarcoplasmic reticulum?

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From the Guidelines

Dantrolene is the agent that relieves spasticity in Multiple Sclerosis (MS) patients by impairing calcium (Ca2+) release from skeletal muscle sarcoplasmic reticulum. The mechanism of action of dantrolene involves direct inhibition of calcium release from the sarcoplasmic reticulum to the cytosol during sustained contraction, thereby reversing muscle rigidity and decreasing production of heat 1. Key points about dantrolene include:

  • It acts directly on the skeletal muscle
  • It is thought to inhibit calcium release from the sarcoplasmic reticulum to the cytosol during sustained contraction
  • It reverses muscle rigidity and decreases production of heat 1
  • Typically, dantrolene is administered orally at a starting dose of 25 mg once daily, gradually increasing to 25-100 mg three to four times daily as needed and tolerated, with a maximum daily dose of 400 mg. The medication works directly on skeletal muscle by binding to ryanodine receptors (RyR1) in the sarcoplasmic reticulum, preventing calcium release and thereby reducing muscle contraction strength. Common side effects include weakness, drowsiness, dizziness, and occasionally liver dysfunction, so liver function tests should be monitored regularly, especially during the first months of treatment. Dantrolene is often reserved for patients who don't respond adequately to first-line antispasticity medications like baclofen or tizanidine due to its potential for liver toxicity. In the context of MS patients, dantrolene's unique mechanism of action makes it a valuable option for managing spasticity, particularly in cases where other treatments have failed or are not tolerated.

From the FDA Drug Label

In skeletal muscle, Dantrium dissociates the excitation-contraction coupling, probably by interfering with the release of Ca++ from the sarcoplasmic reticulum The answer is D dantrolene because it impairs Calcium (Ca2+) release from skeletal muscle sarcoplasmic reticulum, which helps to relieve spasticity in Multiple Sclerosis (MS) patients 2.

From the Research

Agents for Relieving Spasticity in MS Patients

The question asks about the agent that relieves spasticity in Multiple Sclerosis (MS) patients by impairing Calcium (Ca2+) release from skeletal muscle sarcoplasmic reticulum. The correct answer can be identified by examining the mechanism of action of the listed agents.

Mechanism of Action of Agents

  • Dantrolene acts by impairing Ca2+ release from skeletal muscle sarcoplasmic reticulum, which makes it a strong candidate for the correct answer 3, 4, 5, 6.
  • Diazepam acts as a muscle relaxant but its primary mechanism is through the enhancement of GABAergic transmission, not by impairing Ca2+ release from skeletal muscle sarcoplasmic reticulum 3, 7, 5.
  • Tizanidine is an alpha-2 adrenergic agonist that acts centrally to produce its muscle relaxant effects, not by impairing Ca2+ release from skeletal muscle sarcoplasmic reticulum 3, 7, 5.
  • Dalfampridine is a potassium channel blocker used to improve walking in patients with MS, but it does not act by impairing Ca2+ release from skeletal muscle sarcoplasmic reticulum.

Conclusion of Mechanism

Based on the mechanism of action, Dantrolene is the agent that relieves spasticity in MS patients by impairing Ca2+ release from skeletal muscle sarcoplasmic reticulum.

List of Agents and Their Effects

  • A. Diazepam: Enhances GABAergic transmission 3, 7, 5.
  • B. Tizanidine: Acts as an alpha-2 adrenergic agonist 3, 7, 5.
  • C. Dalfampridine: Blocks potassium channels to improve walking in MS patients.
  • D. Dantrolene: Impairs Ca2+ release from skeletal muscle sarcoplasmic reticulum 3, 4, 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anti-spasticity agents for multiple sclerosis.

The Cochrane database of systematic reviews, 2001

Research

Muscle relaxants in multiple sclerosis.

International disability studies, 1987

Research

Treatment of spasticity with tizanidine in multiple sclerosis.

The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 1987

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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