Structure of 24868-20-0
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Dantrolene Sodium is a skeletal muscle relaxant which acts by blocking muscle contraction beyond the neuromuscular junction.
Synonyms: Dantrolene sodium hydrate; Dantrium; F-440
4.5
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| CAS No. : | 24868-20-0 |
| Formula : | C28H32N8Na2O17 |
| M.W : | 798.58 |
| SMILES Code : | [H]O[H].[H]O[H].[H]O[H].[H]O[H].[H]O[H].[H]O[H].[H]O[H].O=C(CN1N=CC2=CC=C(O2)C3=CC=C(C=C3)[N+]([O-])=O)[N-]C1=O.O=C(CN4N=CC5=CC=C(O5)C6=CC=C(C=C6)[N+]([O-])=O)[N-]C4=O.[Na+].[Na+] |
| Synonyms : |
Dantrolene sodium hydrate; Dantrium; F-440
|
| MDL No. : | MFCD07357270 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H302 |
| Precautionary Statements: | P264-P270-P301+P312-P330-P501 |
In Vitro:
|
Cell Line
|
Concentration | Treated Time | Description | References |
| YAC128 MSNs | 100 nM | 1 hour | To evaluate the protective effects of dantrolene on glutamate-induced excitotoxicity in YAC128 MSNs, results showed that dantrolene pretreatment significantly reduced glutamate-induced apoptosis | Mol Neurodegener. 2011 Nov 25;6:81. |
| CPVT-iPSC-derived cardiomyocytes | 10 µM | 10–15 minutes | Dantrolene restored normal Ca2+ spark properties and rescued the arrhythmogenic phenotype in CPVT-iPSC-derived cardiomyocytes under basal conditions and corrected S406L-RYR2 hyperactivity induced by adrenergic stimulation. | EMBO Mol Med. 2012 Mar;4(3):180-91. |
| Rat fetal cortical neurons | 40 µM | 12 hours | To evaluate the protective effect of dantrolene and hypothermia on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury. Results showed that the combination of dantrolene and hypothermia significantly increased neuronal survival, reduced intracellular reactive oxygen species, cytoplasmic histone-associated DNA fragmentation, and apoptosis. | Neural Regen Res. 2015 Aug;10(8):1279-85. |
| Rat mesenteric lymphatic vessels | 3 µM | 20 minutes | Dantrolene prevents DOX-induced 'calcium leak' and maintains rhythmic lymphatic contractions | Front Pharmacol. 2021 Aug 16;12:727526. |
| Induced pluripotent stem cells (iPSCs) | 30 µM | 24 hours | Dantrolene significantly promoted cell viability in iPSCs derived from sporadic Alzheimer’s disease (SAD) and familial Alzheimer’s disease (FAD) patients. | Anesthesiology. 2020 May;132(5):1062-1079. |
| Primary Darier disease patient fibroblasts (DDF) | 10 µM | 24 hours | Dantrolene significantly helped retain ER-Ca2+ levels. | EMBO Mol Med. 2024 Sep;16(9):1986-2001. |
| Primary Darier disease patient keratinocytes (DDK) | 10 µM | 24 hours | Dantrolene significantly reduced baseline and peak levels of cytoplasmic Ca2+ and increased baseline ER-Ca2+ levels, inhibiting Ca2+ efflux. | EMBO Mol Med. 2024 Sep;16(9):1986-2001. |
| Human epidermal keratinocyte (HEKa) | 10 µM | 24 hours | Dantrolene significantly reduced baseline and peak levels of cytoplasmic Ca2+ and increased baseline ER-Ca2+ levels, inhibiting Ca2+ efflux. | EMBO Mol Med. 2024 Sep;16(9):1986-2001. |
| Basal forebrain cholinergic neurons | 30 µM | 3 days | Dantrolene significantly ameliorated the impairment of basal forebrain cholinergic neurons differentiation in both SAD and FAD cells. | Anesthesiology. 2020 May;132(5):1062-1079. |
| Cortical neurons | 30 µM | 3 days | Dantrolene significantly ameliorated the impairment of cortical neurons differentiation in both SAD and FAD cells. | Anesthesiology. 2020 May;132(5):1062-1079. |
| Neuroprogenitor cells | 30 µM | 3 days | Dantrolene significantly ameliorated the impairment of neuroprogenitor cells differentiation into immature neurons in both SAD and FAD cells. | Anesthesiology. 2020 May;132(5):1062-1079. |
| Cardiomyocytes | 10 µM | 30 minutes | To evaluate the effect of Dantrolene on spontaneous SR Ca2+ release, results showed Dantrolene reduced spontaneous Ca2+ release events. | J Mol Cell Cardiol. 2023 Aug;181:67-78. |
| RyR2 channels | 10 µM | To test the inhibitory effect of Dantrolene on RyR2, found that its inhibition depends on the presence of FKBP12.6 | J Gen Physiol. 2023 Aug 7;155(8):e202213277. |
In Vivo:
|
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
| Sprague-Dawley rats | Anesthetized rat mesenteric lymph circulation model | Local mesenteric superfusion | 10 µM | Administered 20 min prior to and continuously after DOX infusion | Dantrolene prevents DOX-induced lymphostasis and maintains lymph flow | Front Pharmacol. 2021 Aug 16;12:727526. |
| Wistar rat pups | KA-induced status epilepticus model | Intraperitoneal injection | 10 mg/kg | Two injections, 1 hour apart | To investigate the protective effect of Dantrolene against KA-induced neuronal apoptosis. Results showed that Dantrolene significantly reduced the number of apoptotic cells in hippocampal CA1 region and parietal cortex. | J Cell Mol Med. 2002 Oct-Dec;6(4):555-69 |
| C57BL/6J mice | Chronic ischemic heart disease model | Subcutaneous osmotic pump | 20 mg/kg | Continuous for 6 weeks | To evaluate the effect of Dantrolene on ventricular tachycardia and cardiac function, results showed Dantrolene reduced VT inducibility, improved cardiac function, and reduced fibrosis. | J Mol Cell Cardiol. 2023 Aug;181:67-78. |
| Mdx mice | Duchenne muscular dystrophy model | Oral | 30–70 mg/kg | Daily for 6 months | Assessed the effect of dantrolene/AON combination on DMD exon-23 skipping, showing dantrolene significantly boosted exon skipping and dystrophin rescue while reducing muscle pathology | Mol Ther Nucleic Acids. 2018 Jun 1;11:180-191 |
| Mice | YAC128 HD transgenic Mice model | Oral | 5 mg/kg | Twice a week from 2 to 11.5 months of age | To evaluate the effects of dantrolene on motor coordination and neuropathology in YAC128 mice, results showed that long-term dantrolene feeding significantly improved motor coordination, reduced striatal neuronal loss, and decreased Htt nuclear aggregate formation | Mol Neurodegener. 2011 Nov 25;6:81. |
| C57BL/6J mice | PS19 tau transgenic mice | Intranasal administration | 5 mg/kg | Once daily, 5 days/week, for 3 months | To investigate the effects of intranasal ERFR on cognitive function in PS19 tau transgenic mice, showing no significant changes in cognition, olfaction, or motor function after chronic treatment. | J Alzheimers Dis. 2024;98(2):549-562 |
Tags: Dantrolene sodium hemiheptahydrate | Dantrolene sodium | Calcium Channel | glutathione reductase inhibitor | RyR antagonist | Ca2+ channels | Ca channels | non-competitive | glutathione reductase | ryanodine receptor | muscle spasticity | malignant hyperthermia | Huntington's disease | neuroleptic malignant syndrome | 24868-20-0
Precautionary Statements-General | |
| Code | Phrase |
| P101 | If medical advice is needed,have product container or label at hand. |
| P102 | Keep out of reach of children. |
| P103 | Read label before use |
Prevention | |
| Code | Phrase |
| P201 | Obtain special instructions before use. |
| P202 | Do not handle until all safety precautions have been read and understood. |
| P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
| P211 | Do not spray on an open flame or other ignition source. |
| P220 | Keep/Store away from clothing/combustible materials. |
| P221 | Take any precaution to avoid mixing with combustibles |
| P222 | Do not allow contact with air. |
| P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
| P230 | Keep wetted |
| P231 | Handle under inert gas. |
| P232 | Protect from moisture. |
| P233 | Keep container tightly closed. |
| P234 | Keep only in original container. |
| P235 | Keep cool |
| P240 | Ground/bond container and receiving equipment. |
| P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
| P242 | Use only non-sparking tools. |
| P243 | Take precautionary measures against static discharge. |
| P244 | Keep reduction valves free from grease and oil. |
| P250 | Do not subject to grinding/shock/friction. |
| P251 | Pressurized container: Do not pierce or burn, even after use. |
| P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
| P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
| P262 | Do not get in eyes, on skin, or on clothing. |
| P263 | Avoid contact during pregnancy/while nursing. |
| P264 | Wash hands thoroughly after handling. |
| P265 | Wash skin thouroughly after handling. |
| P270 | Do not eat, drink or smoke when using this product. |
| P271 | Use only outdoors or in a well-ventilated area. |
| P272 | Contaminated work clothing should not be allowed out of the workplace. |
| P273 | Avoid release to the environment. |
| P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
| P281 | Use personal protective equipment as required. |
| P282 | Wear cold insulating gloves/face shield/eye protection. |
| P283 | Wear fire/flame resistant/retardant clothing. |
| P284 | Wear respiratory protection. |
| P285 | In case of inadequate ventilation wear respiratory protection. |
| P231 + P232 | Handle under inert gas. Protect from moisture. |
| P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
| Code | Phrase |
| P301 | IF SWALLOWED: |
| P304 | IF INHALED: |
| P305 | IF IN EYES: |
| P306 | IF ON CLOTHING: |
| P307 | IF exposed: |
| P308 | IF exposed or concerned: |
| P309 | IF exposed or if you feel unwell: |
| P310 | Immediately call a POISON CENTER or doctor/physician. |
| P311 | Call a POISON CENTER or doctor/physician. |
| P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
| P313 | Get medical advice/attention. |
| P314 | Get medical advice/attention if you feel unwell. |
| P315 | Get immediate medical advice/attention. |
| P320 | |
| P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
| P321 | |
| P322 | |
| P330 | Rinse mouth. |
| P331 | Do NOT induce vomiting. |
| P332 | IF SKIN irritation occurs: |
| P333 | If skin irritation or rash occurs: |
| P334 | Immerse in cool water/wrap n wet bandages. |
| P335 | Brush off loose particles from skin. |
| P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
| P337 | If eye irritation persists: |
| P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
| P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| P342 | If experiencing respiratory symptoms: |
| P350 | Gently wash with plenty of soap and water. |
| P351 | Rinse cautiously with water for several minutes. |
| P352 | Wash with plenty of soap and water. |
| P353 | Rinse skin with water/shower. |
| P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
| P361 | Remove/Take off immediately all contaminated clothing. |
| P362 | Take off contaminated clothing and wash before reuse. |
| P363 | Wash contaminated clothing before reuse. |
| P370 | In case of fire: |
| P371 | In case of major fire and large quantities: |
| P372 | Explosion risk in case of fire. |
| P373 | DO NOT fight fire when fire reaches explosives. |
| P374 | Fight fire with normal precautions from a reasonable distance. |
| P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
| P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
| P378 | |
| P380 | Evacuate area. |
| P381 | Eliminate all ignition sources if safe to do so. |
| P390 | Absorb spillage to prevent material damage. |
| P391 | Collect spillage. Hazardous to the aquatic environment |
| P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
| P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
| P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
| P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
| P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
| P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
| P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
| P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
| P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
| P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
| P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
| P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
| P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
| P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
| P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
| P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
| P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
| P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
| P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
| P370 + P376 | In case of fire: Stop leak if safe to Do so. |
| P370 + P378 | In case of fire: |
| P370 + P380 | In case of fire: Evacuate area. |
| P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
| P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
| Code | Phrase |
| P401 | |
| P402 | Store in a dry place. |
| P403 | Store in a well-ventilated place. |
| P404 | Store in a closed container. |
| P405 | Store locked up. |
| P406 | Store in corrosive resistant/ container with a resistant inner liner. |
| P407 | Maintain air gap between stacks/pallets. |
| P410 | Protect from sunlight. |
| P411 | |
| P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
| P413 | |
| P420 | Store away from other materials. |
| P422 | |
| P402 + P404 | Store in a dry place. Store in a closed container. |
| P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
| P403 + P235 | Store in a well-ventilated place. Keep cool. |
| P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
| P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
| P411 + P235 | Keep cool. |
Disposal | |
| Code | Phrase |
| P501 | Dispose of contents/container to ... |
| P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
| Code | Phrase |
| H200 | Unstable explosive |
| H201 | Explosive; mass explosion hazard |
| H202 | Explosive; severe projection hazard |
| H203 | Explosive; fire, blast or projection hazard |
| H204 | Fire or projection hazard |
| H205 | May mass explode in fire |
| H220 | Extremely flammable gas |
| H221 | Flammable gas |
| H222 | Extremely flammable aerosol |
| H223 | Flammable aerosol |
| H224 | Extremely flammable liquid and vapour |
| H225 | Highly flammable liquid and vapour |
| H226 | Flammable liquid and vapour |
| H227 | Combustible liquid |
| H228 | Flammable solid |
| H229 | Pressurized container: may burst if heated |
| H230 | May react explosively even in the absence of air |
| H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
| H240 | Heating may cause an explosion |
| H241 | Heating may cause a fire or explosion |
| H242 | Heating may cause a fire |
| H250 | Catches fire spontaneously if exposed to air |
| H251 | Self-heating; may catch fire |
| H252 | Self-heating in large quantities; may catch fire |
| H260 | In contact with water releases flammable gases which may ignite spontaneously |
| H261 | In contact with water releases flammable gas |
| H270 | May cause or intensify fire; oxidizer |
| H271 | May cause fire or explosion; strong oxidizer |
| H272 | May intensify fire; oxidizer |
| H280 | Contains gas under pressure; may explode if heated |
| H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
| H290 | May be corrosive to metals |
Health hazards | |
| Code | Phrase |
| H300 | Fatal if swallowed |
| H301 | Toxic if swallowed |
| H302 | Harmful if swallowed |
| H303 | May be harmful if swallowed |
| H304 | May be fatal if swallowed and enters airways |
| H305 | May be harmful if swallowed and enters airways |
| H310 | Fatal in contact with skin |
| H311 | Toxic in contact with skin |
| H312 | Harmful in contact with skin |
| H313 | May be harmful in contact with skin |
| H314 | Causes severe skin burns and eye damage |
| H315 | Causes skin irritation |
| H316 | Causes mild skin irritation |
| H317 | May cause an allergic skin reaction |
| H318 | Causes serious eye damage |
| H319 | Causes serious eye irritation |
| H320 | Causes eye irritation |
| H330 | Fatal if inhaled |
| H331 | Toxic if inhaled |
| H332 | Harmful if inhaled |
| H333 | May be harmful if inhaled |
| H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
| H335 | May cause respiratory irritation |
| H336 | May cause drowsiness or dizziness |
| H340 | May cause genetic defects |
| H341 | Suspected of causing genetic defects |
| H350 | May cause cancer |
| H351 | Suspected of causing cancer |
| H360 | May damage fertility or the unborn child |
| H361 | Suspected of damaging fertility or the unborn child |
| H361d | Suspected of damaging the unborn child |
| H362 | May cause harm to breast-fed children |
| H370 | Causes damage to organs |
| H371 | May cause damage to organs |
| H372 | Causes damage to organs through prolonged or repeated exposure |
| H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
| Code | Phrase |
| H400 | Very toxic to aquatic life |
| H401 | Toxic to aquatic life |
| H402 | Harmful to aquatic life |
| H410 | Very toxic to aquatic life with long-lasting effects |
| H411 | Toxic to aquatic life with long-lasting effects |
| H412 | Harmful to aquatic life with long-lasting effects |
| H413 | May cause long-lasting harmful effects to aquatic life |
| H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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