Muscle relaxant · Antidote
Dantrolene (Ryanodex)
Also called Ryanodex
Indications
- Malignant hyperthermia crisis at any age, with stopping triggers, 100% O₂ and cooling
- Maintenance dosing for at least 24 h after a crisis to prevent recrudescence (MHAUS)
- MH prevention in high-risk patients (label); MHAUS finds it unnecessary with a nontriggering anesthetic
- Neuroleptic malignant syndrome with severe rigidity (off-label)
- Chronic spasticity (oral capsules)
Mechanism of action
Dantrolene binds the type 1 ryanodine receptor (RyR1), the calcium release channel of the skeletal muscle sarcoplasmic reticulum, and stabilizes its closed state; it needs ATP or ADP and Mg²⁺ and raises the channel's affinity for inhibitory Mg²⁺. Less calcium is released per action potential, so contraction weakens while neuromuscular transmission and the muscle action potential are unchanged. In malignant hyperthermia this halts the calcium-driven contracture, ATP use, heat and CO₂ production. Cardiac RyR2 is largely insensitive.
Pharmacology
- Musculoskeletal: dose-related weakness without paralysis; may impair swallowing and breathing; potentiates nondepolarizing blockers
- Metabolic: in MH, EtCO₂, heart rate, temperature, potassium and lactate fall
- CNS: drowsiness and dizziness for up to 48 h (label)
- Cardiovascular: little direct effect on the heart
Pharmacokinetics
| Onset | Minutes; doses are repeated until EtCO₂, rigidity and heart rate improve (MHAUS) |
|---|---|
| Duration | Blood levels stay near steady state for 3 h or more after the infusion (label) |
| Half-life | 4–8 h IV on the 20 mg vial labels; 8.5–11.4 h on the Ryanodex label |
| Distribution | Vd about 36 L (0.5 L/kg); crosses the placenta, with fetal levels near maternal |
| Protein binding | Extensive, mostly albumin |
| Metabolism | Liver: 5-hydroxylation; nitro-reduction by aldehyde oxidase, then NAT2 acetylation; a hydroxylamine intermediate may explain liver injury (Amano 2018) |
| Elimination | Metabolites in urine and bile; under 5% unchanged |
Chemistry
- Hydantoin derivative, the ring family of phenytoin: a nitrophenyl-furan linked to hydantoin by a C=N–N bridge; achiral and orange
- Weak acid, pKa 7.5, a little under half ionized at pH 7.4; log P 1.7; water solubility only about 146 mg/L, so IV forms are alkaline sodium salts
- Dantrium IV and Revonto: 20 mg plus 3 g mannitol per vial (pH 9.5), each mixed with 60 mL preservative-free sterile water; 2.5 mg/kg at 70 kg takes 9 vials and 540 mL
- Ryanodex: 250 mg nanosuspension with 125 mg mannitol, mixed with 5 mL sterile water (50 mg/mL, pH 10.3); one vial covers 2.5 mg/kg up to 100 kg
- Use within 6 h; protect from light; D5W and 0.9% NaCl are incompatible
Adverse effects and cautions
In the one-pagers
- Hypothermia, Heat Stroke and DrowningCooling heat stroke: No antipyretics (harm liver and clotting); no dantrolene (SCCM 2025, strong)
- Toxidromes and AntidotesSerotonin syndrome vs NMS: Treatment: Stop drug, benzodiazepines, cooling, cyproheptadine: Stop drug, cooling, benzodiazepines, bromocriptine, dantrolene
- Behavioral Emergencies, Agitation and AbuseAntipsychotic side effects in the field: Neuroleptic malignant syndrome (Merck): muscle rigidity, hyperthermia, autonomic instability and a raised CK, with rhabdomyolysis and kidney injury; more common with first-generation drugs but possible with all; stop the drug, cool rapidly, aggressive support; bromocriptine, amantadine and dantrolene are hospital drugs. Catatonia and NMS can look the same (
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Sources
- FDA label: Ryanodex (2024)
- FDA label: Revonto (2024)
- MHAUS: dantrolene after an MH event (2017)
- PubChem: dantrolene
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.