NB: A more extensive discussion of all aspects of both difenoxin and diphenoxylate can be found in the article about
DiphenoxylateDiphenoxylate is an opioid agonist used for the treatment of diarrhoea that acts by slowing intestinal contractions and peristalsis allowing the body to consolidate intestinal contents and prolong transit time, thus allowing the intestines to draw moisture out of them at a normal or higher rate...
Difenoxin
(Motofen) is a 4-phenyl
piperidinePiperidine is an organic compound with the molecular formula
5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...
derivative that is related to the
opioidAn opioid is a chemical that works by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract...
analgesicAn analgesic is any member of the diverse group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos...
drug
pethidinePethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Romania); Petidin Dolargan (in Poland);...
(meperidine) and more distantly related to alphaprodine and
piritramidePiritramide is a synthetic opioid analgesic with a potency 0.65 to 0.75 times that of morphine. A common starting dose is 15 mg IV, equivalent to 10 mg of morphine hydrochloride. Piritramide is commonly used for the treatment of postoperative pain...
, and it is an active metabolite of the anti-diarrhoea drug
diphenoxylateDiphenoxylate is an opioid agonist used for the treatment of diarrhoea that acts by slowing intestinal contractions and peristalsis allowing the body to consolidate intestinal contents and prolong transit time, thus allowing the intestines to draw moisture out of them at a normal or higher rate...
. Difenoxin et al. have a high peripheral/central actions ratio, working primarily on various opioid receptors in the intestines.
NB: A more extensive discussion of all aspects of both difenoxin and diphenoxylate can be found in the article about
DiphenoxylateDiphenoxylate is an opioid agonist used for the treatment of diarrhoea that acts by slowing intestinal contractions and peristalsis allowing the body to consolidate intestinal contents and prolong transit time, thus allowing the intestines to draw moisture out of them at a normal or higher rate...
Difenoxin
(Motofen) is a 4-phenyl
piperidinePiperidine is an organic compound with the molecular formula
5NH. This heterocyclic amine consists of a six-membered ring containing five methylene units and one nitrogen atom...
derivative that is related to the
opioidAn opioid is a chemical that works by binding to opioid receptors, which are found principally in the central nervous system and the gastrointestinal tract...
analgesicAn analgesic is any member of the diverse group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos...
drug
pethidinePethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Romania); Petidin Dolargan (in Poland);...
(meperidine) and more distantly related to alphaprodine and
piritramidePiritramide is a synthetic opioid analgesic with a potency 0.65 to 0.75 times that of morphine. A common starting dose is 15 mg IV, equivalent to 10 mg of morphine hydrochloride. Piritramide is commonly used for the treatment of postoperative pain...
, and it is an active metabolite of the anti-diarrhoea drug
diphenoxylateDiphenoxylate is an opioid agonist used for the treatment of diarrhoea that acts by slowing intestinal contractions and peristalsis allowing the body to consolidate intestinal contents and prolong transit time, thus allowing the intestines to draw moisture out of them at a normal or higher rate...
. Difenoxin et al. have a high peripheral/central actions ratio, working primarily on various opioid receptors in the intestines. Difenoxin was developed in 1970 in Belgium at Janssen Pharmaceutica.
Related compounds
LoperamideLoperamide, a synthetic piperidine derivative, is a drug effective against diarrhea resulting from gastroenteritis or inflammatory bowel disease. In most countries it is available generically and under brand names such as Lopex, Imodium, Dimor and Pepto Diarrhea Control...
(Imodium) is also closely related to difenoxin in chemical structure but does not cross the
blood-brain barrierThe blood-brain barrier is a separation of circulating blood and cerebrospinal fluid maintained by the choroid plexus in the central nervous system . Endothelial cells restrict the diffusion of microscopic objects The blood-brain barrier (BBB) is a separation of circulating blood and...
as does difenoxin, and the combination drug diphenoxylate hydrochloride with atropine sulphate (Lomotil) is the prototype of this four-member subfamily of the synthetic
opioid receptorOpioid receptors are a group of G-protein coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin...
agonists and sub-category of opioid anti-diarrhoeals.
PethidinePethidine or meperidine Pethidine (INN) or meperidine (USAN) Pethidine (INN) or meperidine (USAN) (commonly referred to as Demerol but also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil; Alodan; Centralgin; Dispadol; Dolantin; Mialgin (in Romania); Petidin Dolargan (in Poland);...
was serendipitiously discovered in research during the 1930s on gastrointestinal drugs to serve as alternatives to belladonna and
opiumOpium is a narcotic formed from the latex released by lacerating the immature seed pods of opium poppies . It contains up to 12% morphine, an opiate alkaloid, which is most frequently processed chemically to produce heroin for the illegal drug trade...
derivatives, but the anti-diarrhoeal effects of pethidine are less than those of this subclass and equivalent contstipating doses of pethidine have prominent central actions. Therefore, with difenoxin and related drugs, the ratio of GI effects to central narcotic effects is particularly high, which makes it an attractive alternative in the minds of many to the other opioids used for diarrhoea, viz.
codeineCodeine or methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties.-History:Codeine is an alkaloid found in opium and other poppy saps like Papaver bracteatum, the Iranian poppy, in concentrations ranging from 0.3 to 3.0 percent...
,
morphineMorphine is a highly potent opiate analgesic psychoactive drug, is the principal active ingredient in Papaver somniferum , is considered to be the prototypical opioid. Like other opioids, e.g...
,
dihydrocodeineDihydrocodeine, also called DHC, Drocode, Paracodeine and Parzone and known by the brand names of Synalgos DC, Panlor DC, Panlor SS, Contugesic, SS Bron, Drocode, Paracodin, Codidol, Didor Continus, Dicogesic, Codhydrine, Dekacodin, DH-Codeine, Didrate, Dihydrin,...
,
paregoricParegoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties. It was a household remedy in the 18th and 19th centuries, when it was widely used to calm fretful children. In the 20th century...
,
laudanumLaudanum , also known as opium tincture or thebaic tincture is an alcoholic herbal preparation containing approximately 10% opium and 1% morphine . It is made by combining ethanol with opium latex or powder...
and
opiumOpium is a narcotic formed from the latex released by lacerating the immature seed pods of opium poppies . It contains up to 12% morphine, an opiate alkaloid, which is most frequently processed chemically to produce heroin for the illegal drug trade...
. The parent of the three above-mentioned pethidine-related anti-diarrhoeals is diphenoxylic acid, which can also be manufactured and used pharmaceutically.
Legal status
Difenoxin is not used by itself and is a
Schedule IThe Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
drug in the USA, having been approved for use in the late 1990s in the form of Motofen (difenoxin HCl and atropine tablets and elixir) which like
LomotilComprehensive information about Lomotil and allied drugs is under the article Diphenoxylate.Lomotil is the trade name of a popular oral anti-diarrheal drug in the United States, manufactured by Pfizer. Its UK BAN generic name is Co-phenotrope....
is a less-restrictive category
Schedule IVThe Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
on account of the adulterant; one difference is that the diphenoxylate and atropine formulation is
Schedule VThe Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
. Atropine is present in each doseage unit in the amount of 25 µg, or
1/
40 of the therapeutic dose. Many other countries have been using this combination product for many years as a second-line centrally-acting and/or opioid-agonist anti-diarrhoeal, betwixt
loperamideLoperamide, a synthetic piperidine derivative, is a drug effective against diarrhea resulting from gastroenteritis or inflammatory bowel disease. In most countries it is available generically and under brand names such as Lopex, Imodium, Dimor and Pepto Diarrhea Control...
and
paregoricParegoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties. It was a household remedy in the 18th and 19th centuries, when it was widely used to calm fretful children. In the 20th century...
.
Side effects
Diarrhoea resulting from cyclic or diarrhoea-predominant IBS may not be optimally treated with diphenoxylate or difenoxin, and may not respond to a meaningful degree to
loperamideLoperamide, a synthetic piperidine derivative, is a drug effective against diarrhea resulting from gastroenteritis or inflammatory bowel disease. In most countries it is available generically and under brand names such as Lopex, Imodium, Dimor and Pepto Diarrhea Control...
; thus, diarrhoea and cramping which does not respond to belladonna derivatives and non-centrally-acting soothing and/or stool-desiccating agents are often treated with conservative doses of
codeineCodeine or methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties.-History:Codeine is an alkaloid found in opium and other poppy saps like Papaver bracteatum, the Iranian poppy, in concentrations ranging from 0.3 to 3.0 percent...
, especially where
paregoricParegoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a medication known for its antidiarrheal, antitussive, and analgesic properties. It was a household remedy in the 18th and 19th centuries, when it was widely used to calm fretful children. In the 20th century...
and/or
laudanumLaudanum , also known as opium tincture or thebaic tincture is an alcoholic herbal preparation containing approximately 10% opium and 1% morphine . It is made by combining ethanol with opium latex or powder...
are not currently in general use.
Difenoxin also has some
sedativeA sedative is a substance that induces sedation by reducing irritability or excitement.At higher doses it may result in slurred speech, staggering gait, poor judgment, and slow, uncertain reflexes...
and
analgesicAn analgesic is any member of the diverse group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos...
effects as with other opioids, but diphenoxylate itself is a relatively weak analgesic, and difenoxin has similarly limited analgesic effects, although it is a potent anti-diarrheal drug. Research suggests that additional non-opioid mechanisms may also be involved in the action of difenoxin, explaining its strong anti-diarrheal effects despite only limited opioid action.