Dantrolene: A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Dantrolene is a direct-acting, postsynaptic skeletal muscle relaxant belonging to the hydantoin class of compounds. Uniquely, it exerts its therapeutic effects by acting intracellularly to inhibit the release of calcium ions () from the sarcoplasmic reticulum, a mechanism mediated through the direct antagonism of the ryanodine receptor 1 (RyR1).[1] This distinct pharmacological profile establishes Dantrolene's dual and critical roles in modern medicine. Primarily, it stands as the sole, life-saving antidote for Malignant Hyperthermia (MH), a rare but potentially fatal pharmacogenetic emergency triggered by certain anesthetic agents.[1] In this acute setting, its rapid intravenous administration is the cornerstone of treatment. Concurrently, Dantrolene is utilized as a chronic oral therapy for the management of debilitating muscle spasticity arising from various upper motor neuron disorders, such as multiple sclerosis, cerebral palsy, and spinal cord injury.[5] The drug's utility is, however, balanced by a significant safety consideration: a U.S. Food and Drug Administration (FDA) Black Box Warning for potentially fatal hepatotoxicity, a risk predominantly associated with long-term oral administration.[3] Furthermore, its safe use is contingent upon awareness of critical drug-drug interactions, most notably a contraindicated combination with non-dihydropyridine calcium channel blockers like verapamil and diltiazem, which can precipitate life-threatening hyperkalemia and cardiovascular collapse.[2]

Introduction and Historical Development