Tìm theo
Difenoxin
Các tên gọi khác (7 ) :
  • 1-(3-Cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid
  • Difenoxin
  • Difenoxina
  • Difenoxinum
  • Diphenoxilic acid
  • Diphenoxin
  • Diphenoxylic acid
Thuốc Gốc
Small Molecule
CAS: 28782-42-5
ATC: A07DA04
ĐG : Amarin Pharmaceuticals , http://www.amarincorp.com
CTHH: C28H28N2O2
PTK: 424.5341
Difenoxin is a 4-phenylpiperidine which is closely related to the opioid analgesic meperidine. Difenoxin alone is a USA Schedule I controlled drug, as it may be habit forming. However, it is listed as a Schedule IV controlled drug if combined with atropine, which is added to decrease deliberate misuse. Motofen(R) is a brand mixture which combines atropine sulfate and difenoxin hydrochloride. It is approved by the FDA to treat acute and chronic diarrhea. Difenoxin is an active metabolite of the anti-diarrheal drug, diphenoxylate, which is also used in combination with atropine in the brand mixture Lomotil(R). It works mostly in the periphery and activates opioid receptors in the intestine rather than the central nervous system (CNS). [3] Difenoxin is also closely related to loperamide, but unlike loperamide it is still capable of crossing the blood brain barrier to produce weak sedative and analgesic effects. However, the antidiarrheal potency of difenoxin is much greater than its CNS effects, which makes it an attractive alternative to other opioids.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C28H28N2O2
Phân tử khối
424.5341
Monoisotopic mass
424.21507815
InChI
InChI=1S/C28H28N2O2/c29-22-28(24-12-6-2-7-13-24,25-14-8-3-9-15-25)18-21-30-19-16-27(17-20-30,26(31)32)23-10-4-1-5-11-23/h1-15H,16-21H2,(H,31,32)
InChI Key
InChIKey=UFIVBRCCIRTJTN-UHFFFAOYSA-N
IUPAC Name
1-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidine-4-carboxylic acid
Traditional IUPAC Name
difenoxin
SMILES
OC(=O)C1(CCN(CCC(C#N)(C2=CC=CC=C2)C2=CC=CC=C2)CC1)C1=CC=CC=C1
Độ hòa tan
2.08e-03 g/l
logP
2.65
logS
-5.3
pKa (strongest acidic)
3.38
pKa (Strongest Basic)
9.41
PSA
64.33 Å2
Refractivity
137.24 m3·mol-1
Polarizability
47.56 Å3
Rotatable Bond Count
7
H Bond Acceptor Count
4
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
4
Bioavailability
1
Rule of Five
true
MDDR-Like Rule
true
Dược Lực Học : Difenoxin acts as a potent antidiarrheal by slowing the movement of the intestines. It also crosses the blood brain barrier to a slight degree to exert weak sedative and analgesic effects. Adverse reactions thus include dizziness, drowsiness, lightheadedness and headache, in addition to gastrointestal side effects such as nausea, vomiting, dry mouth and epigastric distress. [Lexicomp, 2013]
Cơ Chế Tác Dụng : Difenoxin is a 4-phenylpiperidine which is closely related to the opioid analgesic meperidine. Difenoxin alone is a USA Schedule I controlled drug, as it may be habit forming. However, it is listed as a Schedule IV controlled drug if combined with atropine, which is added to decrease deliberate misuse. Motofen(R) is a brand mixture which combines atropine sulfate and difenoxin hydrochloride. It is approved by the FDA to treat acute and chronic diarrhea. Difenoxin is an active metabolite of the anti-diarrheal drug, diphenoxylate, which is also used in combination with atropine in the brand mixture Lomotil(R). It works mostly in the periphery and activates opioid receptors in the intestine rather than the central nervous system (CNS). [3] Difenoxin is also closely related to loperamide, but unlike loperamide it is still capable of crossing the blood brain barrier to produce weak sedative and analgesic effects. However, the antidiarrheal potency of difenoxin is much greater than its CNS effects, which makes it an attractive alternative to other opioids. Difenoxin acts as an antidiarrheal by activating peripheral opioid receptors in the small intestine and thereby inhibiting peristalsis. However, research has suggested that non-opioid receptor pathways exist. This would explain the potent antidiarrheal effects of difenoxin despite only limited opioid action [1].
Dược Động Học :
▧ Absorption :
A high percentage of Motofen(R) is absorbed, and absorption occurs rapidly. Peak plasma concentrations are achieved within 40-60 minutes. [Lexicomp, 2013]
▧ Metabolism :
Metabolism occurs by hydroxylation to form an inactive metabolite. [Lexicomp, 2013]
▧ Route of Elimination :
Both the drug and its metabolites are excreted, mainly as conjugates, in urine and feces. [Lexicomp, 2012]
▧ Half Life :
The elimination half life was calculated to be 7.24 hours. The appearance half life was calculated to be 0.82h. [3]
Chỉ Định : Motofen(R) is a combination of atropine, an anticholinergic drug, and difenoxin, an antidiarrheal drug. It has been used in many countries for many years as a second line opioid-agonist antidiarrheal, which exists an intermediate between loperamide and paragoric. [2] Diarrhea which is a result of cyclic or diarrhea predominant Inflammatory Bowel Syndrome may not be treated effectively with difenoxin, diphenoxylate, or loperamide. As such, diarrhea and cramping which does not respond to non-centrally acting derivatives or belladonna derivatives such as atropine are often treated with conservative doses of codeine. In patients with acute ulcerative colitis, as induction of toxic megacolon is possible, and thus use of Motofen(R) is cautioned. Motofen(R) has been assigned pregnancy category C by the FDA, and is to be used only when the potential benefits outweigh the potential risk to the fetus. The safety of use during lactation is unknown and thus not recommended.
Tương Tác Thuốc :
  • Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Liều Lượng & Cách Dùng : Tablet - Oral - 1mg difenoxin HCl/0.025mg atropine sulfate
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : Janssen
    Sản phẩm biệt dược : Lyspafen
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01501
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=34328
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508854
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07871
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D03809
ChemSpider
http://www.chemspider.com/Chemical-Structure.31620.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0187-0500-01
Wikipedia
http://en.wikipedia.org/wiki/Difenoxin
RxList
http://www.rxlist.com/motofen-drug.htm
PDRhealth
http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a07005a9-6f31-4cd6-9abf-334a9a882551
Drugs.com
http://www.drugs.com/cdi/motofen.html
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