Tìm theo
Methylnaltrexone
Các tên gọi khác (2) :
  • Methylnaltrexone
  • MNTX
narcotic antagonists
Thuốc Gốc
Small Molecule
CAS: 73232-52-7
ATC: A06AH01
CTHH: C21H26NO4
PTK: 356.4354
Methylnaltrexone is a pheriphally-acting μ-opioid antagonists that acts on the gastrointestinal tract to decrease opioid-induced constipation without producing analgesic effects or withdrawal symptoms. It is also a weak CYP2D6 inhibitor. FDA approved in 2008.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C21H26NO4
Phân tử khối
356.4354
Monoisotopic mass
356.186183325
InChI
InChI=1S/C21H25NO4/c1-22(11-12-2-3-12)9-8-20-17-13-4-5-14(23)18(17)26-19(20)15(24)6-7-21(20,25)16(22)10-13/h4-5,12,16,19,25H,2-3,6-11H2,1H3/p+1/t16-,19+,20+,21-,22?/m1/s1
InChI Key
InChIKey=JVLBPIPGETUEET-GAAHOAFPSA-O
IUPAC Name
(1S,5R,13R,17S)-4-(cyclopropylmethyl)-10,17-dihydroxy-4-methyl-14-oxo-12-oxa-4-azapentacyclo[9.6.1.0¹,¹³.0⁵,¹⁷.0⁷,¹⁸]octadeca-7,9,11(18)-trien-4-ium
Traditional IUPAC Name
methylnaltrexone
SMILES
[H][C@@]12OC3=C(O)C=CC4=C3[C@@]11CC[N+](C)(CC3CC3)[C@]([H])(C4)[C@]1(O)CCC2=O
Độ hòa tan
≥5 mg/mL
logP
2.200
logS
-4.7
pKa (strongest acidic)
7.4
pKa (Strongest Basic)
-3.9
PSA
66.76 Å2
Refractivity
107.42 m3·mol-1
Polarizability
38.12 Å3
Rotatable Bond Count
2
H Bond Acceptor Count
4
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
6
Bioavailability
1
Rule of Five
true
Dược Lực Học : Use of opioids induces slowing of gastrointestinal motility and transit. Following remifentanil administration, the methylnaltrexone and placebo groups showed no change in pupiliary constriction while the naloxone group showed a marked change over the time interval tested.
Cơ Chế Tác Dụng : Methylnaltrexone is a pheriphally-acting μ-opioid antagonists that acts on the gastrointestinal tract to decrease opioid-induced constipation without producing analgesic effects or withdrawal symptoms. It is also a weak CYP2D6 inhibitor. FDA approved in 2008. Methylnaltrexone is a pheriphally-acting μ-opioid antagonists that acts on the gastrointestinal tract inhibit opioid-induced decrease in gastric motility and transit time. Because methylnaltrexone is a quaternary derivative of naltrexone, it produces its gastrointestinal effects without producing analgesic effects or withdrawal symptoms as it does not cross the blood-brain-barrier.
Dược Động Học :
▧ Absorption :
Methylnaltrexone is rapidly absorbed. Tmax (SubQ): 30 minutes (regardless of dose); Cmax, 0.15 mg/kg SubQ dose = 117 ng/mL; AUC24, 0.15 mg/kg SubQ dose = 175 ng·hr/mL;
▧ Volume of Distribution :
Volume of distribution, steady state = 1.1 L/kg
▧ Protein binding :
11% to 15% bound to human plasma proteins.
▧ Metabolism :
60% of the dose is metabolized. Conversion to methyl-6-naltrexol isomers (5% of total dose) and methylnaltrexone sulfate (1.3% of total dose) appear to be the primary pathways of metabolism. N‑demethylation of methylnaltrexone to produce naltrexone is not significant.
▧ Route of Elimination :
Most of the drug is eliminated as unchanged drug (85% of administered radioactivity). Approximately half of the dose is excreted in the urine and somewhat less in feces.
▧ Half Life :
terminal: 8.89 ± 2.59 h (intravenous) terminal: 6.14- 8.83 h (subcutaneous)
▧ Clearance :
10.5 ± 1.5 ml/min/kg (IV)
Độc Tính : LD50: 50 mg/kg (primates); Orthostatic hypotension at plasma levels in excess of 1.400 ng/mL. The most common (>5%) adverse reactions reported with methylnaltrexone bromide are abdominal pain, flatulence, nausea, dizziness, diarrhea and hyperhidrosis.
Chỉ Định : Treatment of opioids induced constipation in palliative patients that are inadequately responding to laxative therapy.
Liều Lượng & Cách Dùng : Injection, solution - Subcutaneous - 12 mg/0.6 mL
Injection, solution - Subcutaneous - 8 mg/0.4 mL
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB06800
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D06618
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0008-1225-10
Wikipedia
http://en.wikipedia.org/wiki/Methylnaltrexone
RxList
http://www.rxlist.com/relistor-drug.htm
Drugs.com
http://www.drugs.com/cdi/methylnaltrexone.html
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