Difenoxin

Difenoxin

Clinical data
AHFS/Drugs.com	International Drug Names
ATC code	A07DA04 (WHO)
Legal status
Legal status	AU: S8 (Controlled) CA: Schedule I DE: Anlage II (Prohibited) US: Schedule I (by itself); Schedule IV (with atropine)
Identifiers
IUPAC name 1-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidine-4-carboxylic acid
Synonyms	Difenoxin, Motofen
CAS Number	35607-36-4 N
PubChem CID	34328
IUPHAR/BPS	7592
DrugBank	DB01501 Y
ChemSpider	31620 Y
UNII	3ZZ5BJ9F2Q
KEGG	D03809 Y
ChEBI	CHEBI:4534 Y
ChEMBL	CHEMBL1201321 N
Chemical and physical data
Formula	C28H28N2O2
Molar mass	424.53 g/mol
3D model (Jmol)	Interactive image
SMILES C(CCN1CCC(CC1)(C(O)=O)C2=CC=CC=C2)(C3=CC=CC=C3)(C4=CC=CC=C4)C#N
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) Y Key:UFIVBRCCIRTJTN-UHFFFAOYSA-N Y
NY (what is this?)

Difenoxin (Motofen, R-15403) is an opioid drug used, often in combination with atropine, to treat diarrhea. It is the principal metabolite of diphenoxylate.

Difenoxin crosses the blood brain barrier and induces some euphoria; it is often sold with or administered with atropine to reduce the potential for abuse and overdose. At high doses there are strong CNS effects and the atropine at such high doses causes typical anticholinergic side effects, such as anxiety, dysphoria, and delirium. Excessive use or overdose causes constipation and can promote development of megacolon. In the 1990s its use in children was restricted in many countries due to the CNS side effects, which included anorexia, nausea and vomiting, headache, drowsiness, confusion, insomnia, dizziness, restlessness, euphoria and depression.

Difenoxin has a high peripheral/central actions ratio, working primarily on various opioid receptors in the intestines. Although it is capable of producing significant central effects at high doses, doses within the normal therapeutic range generally do not notably impair cognition or proprioception, resulting in therapeutic activity roughly equatable to that of loperamide (Imodium). Increased dosages result in more prominent central opioid effects (and anticholingeric effects when the formulation also contains a tropane alkaloid). It therefor offers limited advantages over more potent anti-diarrheal opioid options (ex. morphine) when treating intractable cases of diarrhea which fail to respond to normal or moderately increased difenoxin doses, and may in fact be harmful in such circumstances if the formulation used also contains atropine or hyoscyamine.

Difenoxin is a Schedule I drug by itself in the US; the combination with atropine is in the less-restrictive category Schedule IV on account of the adulterant (the practice of making opioids more easily available by including an abuse-deterring adulterating agent is standard practice in the United States). Pure difenoxin, in Schedule I, has a quota of 50 grammes, and an ACSCN of 9168. The combination of difenoxin and atropine, in Schedule IV, has the DEA ACSCN of 9167 and being in Schedule IV is not assigned an aggregate annual manufacturing quota.