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DB01501 - Difenoxin


Identification
Name Difenoxin
Accession Number DB01501
Type small molecule
Description 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.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 424.5341
Groups illicit
Monoisotopic Weight 424.21507815
Pharmacology
Indication 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.
Mechanism of action Difenoxin acts as an antidiarrheal by activating peripheral opioid receptors in the small intestine and thereby inhibit 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].
Absorption A high percentage of Motofen(R) is absorbed, and absorption occurs rapidly. Peak plasma concentrations are achieved within 40-60 minutes. [Lexicomp, 2013]
Protein binding Not Available
Biotransformation 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]
Toxicity Not Available
Affected organisms Not Available
Interactions
Drug Interactions
Drug Mechanism of interaction
Alvimopan Increases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
Food Interactions
  • Ethanol use may increase CNS depression.

Predictions


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