Dantrium-Mechanism of Action in Muscle Relaxation

1. Dantrium: Mechanism of Action in Muscle Relaxation Muscle Spasticity and Malignant Hyperthermia Overview Muscle spasticity is characterized by abnormal tightness or stiffness of muscles, often resulting from neurological injuries or diseases such as cerebral palsy, stroke, or multiple sclerosis.1 Malignant hyperthermia is an autosomal dominant skeletal muscle disorder that typically manifests as a hypermetabolic reaction to triggering agents, such as halogenated anaesthetic gases or the depolarizing muscle relaxant succinylcholine. It is caused by mutations in the ryanodine receptor gene, which regulates the release of calciumin muscle cells.in muscle cells. Without prompt treatment, it can result in severe complications, including cardiac arrest, kidney failure, and death.2 What Is Dantrium (Dantrolene)? Dantrium (Dantrolene Sodium) is a muscle relaxant used to treat malignant hyperthermia. It is used in combination with supportive measures and also serves as a preventive therapy for individuals at high risk of developing malignant hyperthermia.3,4 Mechanism of Action: Effect on Calcium Release Dantrium’s hallmark mechanism is its effect on calcium ions within skeletal muscle cells. Skeletal muscle contraction depends on calcium release from the sarcoplasmic reticulum, a specialized storage site inside muscle cells. This process is mediated by ryanodine receptor type 1 channels. Dantrium binds directly to the ryanodine receptor type 1, inhibiting its activity and thereby reducing the outflow of calcium from the sarcoplasmic reticulum. With less calcium available, muscle fibers are less able to contract forcefully, resulting in muscle relaxation. In malignant hyperthermia, this mechanism is lifesaving—by preventing excessive calcium accumulation, Dantrium reestablishes myoplasmic calcium equilibrium, curtailing the crisis and preventing catastrophic metabolic consequences.3 Approved Clinical Uses •Dantrium is FDA-approved for the treatment of malignant hyperthermia in adults and children.

2. •It is also approved for muscle spasticity disorders due to upper motor neuron conditions, including stroke, spinal cord injury, cerebral palsy, and multiple sclerosis. •Dantrium is the only FDA-approved oral, peripherally-acting antispasmodic for managing these spasticity-related disorders.3 Safety and Side Effects •Intravenous Dantrium may cause skeletal muscle weakness, dyspnea, and reduced inspiratory capacity, consistent with its muscle-relaxing action. •Oral Dantrium carries a risk of liver injury, including hepatitis. Liver function should be assessed before starting treatment and monitored regularly to ensure optimal outcomes. •Discontinue the drug if liver impairment occurs. Contraindications •Intravenous Dantrium has no contraindications for treating malignant hyperthermia. •Oral Dantrium is contraindicated in patients with underlying liver disease (cirrhosis, non- alcoholic steatohepatitis, hepatitis B/C). Pregnancy and Breastfeeding •Dantrium is classified as anFDA pregnancy category C medication; it may be used for the treatment ofmalignant hyperthermia, but alternatives are preferred for other indications. •Breastfeeding should be discontinued during treatment and for 48 hours after cessation. Monitoring and Reinitiation •For oral use in muscle spasticity, monitor liver function tests; discontinue if liver injury signs appear (elevated LFTs, jaundice, right upper quadrant pain). •If therapy is restarted, it should be initiated with a gradual dose escalation.3 Conclusion Dantrium remains the only specific pharmacologic antidote for malignant hyperthermia and an important option for treating chronic muscle spasticity from severe neurologic disorders. Its unique mechanism, which blocks calcium release via ryanodine receptor type 1 channels, sets it apart from other muscle relaxants and underpins its clinical efficacy. While highly effective, safety considerations, such as monitoring for hepatotoxicity, should be maintained throughout therapy, to ensure optimal patient outcomes.

3. Note: This content is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified healthcare provider with any questions regarding a medical condition or treatment. Disclaimer: Rx4U procures prescribed medicines directly from manufacturers or authorized distributors. It does not claim ownership of any trademarks and complies with the provisions of the Trademark Act, 1999, particularly Sections 30 and 30(1) concerning ‘Fair Use’. It solely facilitates access to new launches through named patient import. References 1.Milligan J, Ryan K, Lee J. Demystifying spasticity in primary care. Canadian Family Physician [Internet]. 2019 Oct;65(10):697. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6788672/ 2.Watt S, McAllister RK. Malignant hyperthermia [Internet]. PubMed. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430828/ 3.Ratto D, Joyner RW. Dantrolene [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535398/ 4.Dantrium® Intravenous (dantrolene sodium for injection) Prescribing Information [Internet]. fda.gov; 2007. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018264s025lbl.pdf