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Dantrolene | CAS No: 7261-97-4 | GMP-certified suppliers
A medication that manages and prevents malignant hyperthermia by relaxing skeletal muscles to control hypermetabolic crisis during anesthesia in patients of all ages.
Therapeutic categories
Primary indications
- For use, along with appropriate supportive measures, for the management of the fulminant hypermetabolism of skeletal muscle characteristic of malignant hyperthermia crises in patients of all ages
- Also used preoperatively, and sometimes postoperatively, to prevent or attenuate the development of clinical and laboratory signs of malignant hyperthermia in individuals judged to be malignant hyperthermia susceptible
Product Snapshot
- Dantrolene is available in oral and injectable formulations, including capsules, powders for solution, and suspensions suitable for intravenous and parenteral administration
- Its primary therapeutic use is the management and prevention of malignant hyperthermia crises characterized by skeletal muscle hypermetabolism
- The product is approved and marketed in key North American regulatory markets, specifically the United States and Canada
Clinical Overview
Pharmacologically, dantrolene acts as a direct-acting skeletal muscle relaxant. Unlike other hydantoin derivatives, it does not possess antiepileptic activity. Its mechanism involves binding to the ryanodine receptor 1 (RyR1) located on the sarcoplasmic reticulum of skeletal muscle cells. By modulating this receptor, dantrolene decreases the release of intracellular calcium, thereby disrupting excitation-contraction coupling and reducing elevated myoplasmic calcium concentrations characteristic of malignant hyperthermia. This calcium modulation is critical because excessive intracellular calcium triggers uncontrolled muscle contraction and hypermetabolism in affected patients.
Key pharmacodynamic properties include dissociation of excitation-contraction coupling beyond the myoneural junction, resulting in skeletal muscle relaxation. Dantrolene’s effects counteract the acute cellular catabolic cascade initiated by triggering agents like volatile anesthetics and depolarizing neuromuscular blockers. This action restores calcium homeostasis within muscle cells, attenuating the clinical and laboratory manifestations of malignant hyperthermia.
From an ADME perspective, dantrolene is absorbed following administration and distributes primarily to skeletal muscle tissue. It is metabolized hepatically, and hepatotoxicity has been noted as a safety consideration, warranting monitoring during therapy. Other safety concerns include potential muscle weakness and central nervous system depressant effects.
Notable branded formulations include Dantrium, which has established clinical usage globally in malignant hyperthermia crises and prevention.
For API procurement, sourcing should ensure compliance with established pharmaceutical-grade purity and stability standards due to the critical nature of dantrolene in emergency treatments. Batch consistency and reliable supplier quality management are essential to support regulatory submissions and clinical efficacy.
Identification & chemistry
| Generic name | Dantrolene |
|---|---|
| Molecule type | Small molecule |
| CAS | 7261-97-4 |
| UNII | F64QU97QCR |
| DrugBank ID | DB01219 |
Pharmacology
| Summary | Dantrolene acts as a direct skeletal muscle relaxant by binding to ryanodine receptor 1 (RyR1) and inhibiting calcium release from the sarcoplasmic reticulum, thereby disrupting excitation-contraction coupling. Its primary pharmacodynamic effect is the reduction of intracellular calcium concentration, which mitigates the hypermetabolic response characteristic of malignant hyperthermia. This mechanism targets skeletal muscle tissue abnormalities triggered during malignant hyperthermia crises. |
|---|---|
| Mechanism of action | Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor 1, and decreasing intracellular calcium concentration. Ryanodine receptors mediate the release of calcium from the sarcoplasmic reticulum, an essential step in muscle contraction. |
| Pharmacodynamics | Dantrolene is classified as a direct-acting skeletal muscle relaxant. It is currently the only specific and effective treatment for malignant hyperthermia. In isolated nerve-muscle preparation, Dantrium has been shown to produce relaxation by affecting the contractile response of the muscle at a site beyond the myoneural junction. In skeletal muscle, Dantrium dissociates excitation-contraction coupling, probably by interfering with the release of Ca<sup>2+</sup> from the sarcoplasmic reticulum. In the anesthetic-induced malignant hyperthermia syndrome, evidence points to an intrinsic abnormality of skeletal muscle tissue. In selected humans, it has been postulated that “triggering agents” (e.g.,general anesthetics and depolarizing neuromuscular blocking agents) produce a change within the cell which results in an elevated myoplasmic calcium. This elevated myoplasmic calcium activates acute cellular catabolic processes that cascade to the malignant hyperthermia crisis. It is hypothesized that addition of Dantrium to the “triggered” malignant hyperthermic muscle cell reestablishes a normal level of ionized calcium in the myoplasm. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Ryanodine receptor 1 | Humans | antagonist |
ADME / PK
| Absorption | Bioavailability is 70%. |
|---|---|
| Half-life | The mean biologic half-life after intravenous administration is variable, between 4 to 8 hours under most experimental conditions, while oral is 8.7 hours for a 100mg dose. |
| Protein binding | Significant, mostly to albumin. |
| Metabolism | Hepatic, most likely by hepatic microsomal enzymes. Its major metabolites in body fluids are 5-hydroxydantrolene and an acetylamino metabolite of dantrolene. Another metabolite with an unknown structure appears related to the latter. Dantrium may also undergo hydrolysis and subsequent oxidation forming nitrophenylfuroic acid. |
Formulation & handling
- Dantrolene is a small molecule available for both oral and intravenous administration, including capsules and injectable solutions.
- The compound exhibits low water solubility, necessitating appropriate formulation strategies for parenteral preparations.
- Oral absorption of dantrolene is not affected by food, allowing flexible dosing relative to meals.
Regulatory status
| Lifecycle | The API is currently in a mature stage in the US and Canada markets, with key patents expiring between mid-2022 and mid-2025, allowing for increased generic entry and competition. |
|---|
| Markets | US, Canada |
|---|
Supply Chain
| Supply chain summary | Dantrolene is supplied by multiple packagers primarily serving the US and Canadian markets, with branded products marketed under the name Dantrium. The presence of multiple recent patents in the United States extending into 2023 and beyond indicates ongoing patent protection, suggesting limited generic competition in these regions at this time. The supply landscape includes a mix of pharmaceutical distributors and specialized packagers, supporting a diversified sourcing network. |
|---|
Safety
| Toxicity | Oral LD<sub>50</sub> in rats is 7400 mg/kg. Symptoms which may occur in case of overdose include, but are not limited to, muscular weakness and alterations in the state of consciousness (e.g., lethargy, coma), vomiting, diarrhea, and crystalluria. |
|---|
- Handle with care to avoid ingestion
- Oral LD50 in rats is 7400 mg/kg indicating moderate acute toxicity
- Exposure may cause symptoms including muscular weakness, altered consciousness, vomiting, diarrhea, and crystalluria
Dantrolene is a type of Muscle relaxants
Muscle relaxants are a subcategory of pharmaceutical active pharmaceutical ingredients (APIs) commonly used to alleviate muscle spasms and promote muscle relaxation. These medications act on the central nervous system (CNS) or directly on muscle fibers to reduce muscle tone and tension.
Muscle relaxants can be classified into two main groups: spasmolytics and neuromuscular blockers. Spasmolytics primarily target the CNS to inhibit the transmission of nerve signals, thus reducing muscle spasms. They are often prescribed for conditions such as back pain, muscle strains, and spasms caused by neurological disorders.
Neuromuscular blockers, on the other hand, act at the neuromuscular junction to prevent the transmission of nerve impulses, resulting in temporary paralysis of skeletal muscles. These medications are primarily used during surgical procedures to induce muscle relaxation and facilitate intubation.
Commonly prescribed muscle relaxants include benzodiazepines, such as diazepam and lorazepam, which have sedative properties and can provide relief from muscle spasms. Another class of muscle relaxants is the centrally acting skeletal muscle relaxants, including carisoprodol and cyclobenzaprine, which work by affecting neurotransmitters in the CNS.
It is important to note that muscle relaxants can cause side effects such as drowsiness, dizziness, and impaired coordination. They should only be used under the guidance of a healthcare professional, and the dosage and duration of treatment should be strictly followed to avoid dependence or other complications.
In conclusion, muscle relaxants are pharmaceutical APIs used to alleviate muscle spasms and promote muscle relaxation. They are available in different forms and can target the CNS or directly act on muscle fibers. It is crucial to consult a healthcare professional for proper diagnosis, prescription, and monitoring when using muscle relaxants.
Dantrolene (Muscle relaxants), classified under Skeletal muscle relaxants
Skeletal muscle relaxants are a category of pharmaceutical active pharmaceutical ingredients (APIs) that are commonly used in the treatment of musculoskeletal conditions characterized by muscle spasms, stiffness, or tension. These medications work by targeting the central nervous system to reduce muscle activity and promote relaxation.
Skeletal muscle relaxants act on various receptors in the central nervous system, such as gamma-aminobutyric acid (GABA) receptors, to inhibit the transmission of nerve impulses and decrease muscle tone. This results in a reduction in muscle spasms, pain relief, and improved mobility.
There are different classes of skeletal muscle relaxants, including benzodiazepines, antispasmodics, and centrally acting muscle relaxants. Benzodiazepines, such as diazepam and lorazepam, exert their muscle relaxant effects by enhancing the activity of GABA receptors. Antispasmodics like cyclobenzaprine work by inhibiting the release of certain neurotransmitters involved in muscle contractions. Centrally acting muscle relaxants, such as baclofen and tizanidine, directly target the spinal cord to reduce muscle hyperactivity.
Skeletal muscle relaxants are commonly prescribed for conditions like muscle spasms, back pain, fibromyalgia, and multiple sclerosis. However, they are typically used for short-term treatment due to their potential side effects, including drowsiness, dizziness, and sedation.
It is important to note that skeletal muscle relaxants should only be used under the supervision and prescription of a qualified healthcare professional. Proper dosage and duration of treatment should be determined based on the patient's condition and medical history to ensure safe and effective use of these medications.
Dantrolene API manufacturers & distributors
Compare qualified Dantrolene API suppliers worldwide. We currently have 3 companies offering Dantrolene API, with manufacturing taking place in 2 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| Global Pharma Tek | Distributor | India | India | BSE/TSE, CoA, FDA, GMP, ISO9001, MSDS | 484 products |
| Helsinn Advanced Synthesi... | Producer | Switzerland | Switzerland | CoA, JDMF | 3 products |
| SETV Global | Producer | India | India | CoA, FDA, GMP | 515 products |
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