Tìm theo
Dantrolene
Các tên gọi khác (8 ) :
  • Dantamacrin
  • Dantrium
  • Dantrolene
  • Dantroleno
  • Dantrolenum
  • F-368
  • SID26756482
  • SID26756773
muscle relaxants central
Thuốc Gốc
Small Molecule
CAS: 7261-97-4
ATC: M03CA01
ĐG : Amerisource Health Services Corp. , http://www.amerisourcebergen.com
CTHH: C14H10N4O5
PTK: 314.253
Chemically, dantrolene is a hydantoin derivative, but does not exhibit antiepileptic activity like other hydantoin derivates such as phenytoin.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C14H10N4O5
Phân tử khối
314.253
Monoisotopic mass
314.06511945
InChI
InChI=1S/C14H10N4O5/c19-13-8-17(14(20)16-13)15-7-11-5-6-12(23-11)9-1-3-10(4-2-9)18(21)22/h1-7H,8H2,(H,16,19,20)/b15-7+
InChI Key
InChIKey=OZOMQRBLCMDCEG-VIZOYTHASA-N
IUPAC Name
1-({[5-(4-nitrophenyl)furan-2-yl]methylidene}amino)imidazolidine-2,4-dione
Traditional IUPAC Name
dantrolene
SMILES
[O-][N+](=O)C1=CC=C(C=C1)C1=CC=C(O1)C=NN1CC(=O)NC1=O
Độ tan chảy
279-280 °C
Độ hòa tan
Low (146 mg/L)
logP
1.70
logS
-3.6
pKa (strongest acidic)
9.23
pKa (Strongest Basic)
-1.4
PSA
120.73 Å2
Refractivity
78.87 m3·mol-1
Polarizability
29.98 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
5
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : 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 Ca2+ 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.
Cơ Chế Tác Dụng : Chemically, dantrolene is a hydantoin derivative, but does not exhibit antiepileptic activity like other hydantoin derivates such as phenytoin. 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.
Dược Động Học :
▧ Absorption :
Bioavailability is 70%.
▧ 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.
▧ 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.
Độc Tính : Oral LD50 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • Atazanavir Atazanavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if atazanavir is initiated, discontinued or dose changed.
  • Clarithromycin Clarithromycin may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if clarithromycin is initiated, discontinued or dose changed.
  • Conivaptan Conivaptan may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if conivaptan is initiated, discontinued or dose changed.
  • Darunavir Darunavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if darunavir is initiated, discontinued or dose changed.
  • Delavirdine Delavirdine may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if delavirdine is initiated, discontinued or dose changed.
  • Fosamprenavir Fosamprenavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if fosamprenavir is initiated, discontinued or dose changed.
  • Imatinib Imatinib may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if imatinib is initiated, discontinued or dose changed.
  • Indinavir Indinavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if indinavir is initiated, discontinued or dose changed.
  • Isoniazid Isoniazid may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if isoniazid is initiated, discontinued or dose changed.
  • Itraconazole Itraconazole may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if itraconazole is initiated, discontinued or dose changed.
  • Ketoconazole Ketoconazole may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if ketoconazole is initiated, discontinued or dose changed.
  • Lopinavir Lopinavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if lopinavir is initiated, discontinued or dose changed.
  • Methotrimeprazine Concomitant therapy may result in additive CNS depressant effects. The dosage of dantrolene should be decreased by 50% prior to initiating concomitant therapy. Monitor for increased CNS depression.
  • Nefazodone Nefazodone may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if nefazodone is initiated, discontinued or dose changed.
  • Nelfinavir Nelfinavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if nelfinavir is initiated, discontinued or dose changed.
  • Nicardipine Nicardipine may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if nicardipine is initiated, discontinued or dose changed.
  • Posaconazole Posaconazole may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if posaconazole is initiated, discontinued or dose changed.
  • Quinidine Quinidine may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if quinidine is initiated, discontinued or dose changed.
  • Ritonavir Ritonavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if ritonavir is initiated, discontinued or dose changed.
  • Saquinavir Saquinavir may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if saquinavir is initiated, discontinued or dose changed.
  • Telithromycin Telithromycin may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if telithromycin is initiated, discontinued or dose changed.
  • Triprolidine The CNS depressants, Triprolidine and Dantrolene, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Capsule - Oral
Powder, for solution - Intravenous
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : Spepharm
    Sản phẩm biệt dược : Dantamacrin
  • Công ty : Astellas
    Sản phẩm biệt dược : Dantrium
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01219
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C06939
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D02347
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/27505-001-66
PharmGKB
http://www.pharmgkb.org/drug/PA449208
Wikipedia
http://en.wikipedia.org/wiki/Dantrolene
RxList
http://www.rxlist.com/cgi/generic/dantrolene.htm
Drugs.com
http://www.drugs.com/cdi/dantrolene.html
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