Diphenoxylate
Diphenoxylate Basic information
- Product Name:
- Diphenoxylate
- Synonyms:
-
- DIPHENOXYLATE
- 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylicacidethylester
- 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylicaciethyl
- 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecoticacidethylester
- 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-isonipecoticacidethylester
- 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-isonipecoticaciethylester
- 2,2-diphenyl-4-(4-carbethoxy-4-phenylpiperidino)butyronitrile
- ethyl1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylate
- CAS:
- 915-30-0
- MF:
- C30H32N2O2
- MW:
- 452.59
- EINECS:
- 213-020-1
- Mol File:
- 915-30-0.mol
Diphenoxylate Chemical Properties
- Boiling point:
- 602.3±55.0 °C(Predicted)
- Density
- 1.123±0.06 g/cm3(Predicted)
- pka
- pKa 7.1 (Uncertain)
- CAS DataBase Reference
- 915-30-0(CAS DataBase Reference)
- NIST Chemistry Reference
- Diphenoxylate(915-30-0)
Safety Information
- Hazard Codes
- T+
- Risk Statements
- 26/27/28-42/43
- Safety Statements
- 22-26-45
- Hazardous Substances Data
- 915-30-0(Hazardous Substances Data)
- Toxicity
- Diphenoxylate is an antiperistaltic, antidiarrheal drug that is also listed as a controlled substance (opiate).
MSDS
- Language:English Provider:Diphenoxylate
Diphenoxylate Usage And Synthesis
Originator
Lomotil,Searle,US,1960
Uses
Antiperistaltic.
Uses
This drug is a structural analog of meperidine and loperamide; however, it practically duplicates all of the pharmacological properties of loperamide. Being analogous to loperamide, it is mainly used for treating diarrhea. Synonyms for this drug are fentanest, leprofen, and others.
Indications
Diphenoxylate (marketed in combination with atropine as Lomotil in the United States) is chemically related to both analgesic and anticholinergic compounds. It is as effective in the treatment of diarrhea as the opium derivatives, and at the doses usually employed, it has a low incidence of central opioid actions. Diphenoxylate is rapidly metabolized by ester hydrolysis to the biologically active metabolite difenoxylic acid.
Definition
ChEBI: A piperidinecarboxylate ester that is the ethyl ester of difenoxin.
Manufacturing Process
A mixture of 23 parts of the ethyl ester of 4-phenylisonipecotic acid and 15
parts of 2,2-diphenyl-4-
omobutyronitrile in 19 parts of xylene is heated for
24 hours at 100-120°C and then cooled and filtered to remove the precipitate
of the hydro
omide of the ethyl ester of 4-phenylisonipecotic acid. The
filtrate is then extracted with dilute hydrochloric acid and the extract is
rendered alkaline by addition of concentrated aqueous potassium hydroxide
and extracted with ether. This ether extract is treated with gaseous hydrogen
chloride. The resulting precipitate is collected on a filter. The hydrochloride of
the ethyl ester of 2,2-diphenyl-4-(4'-carboxy-4'-phenyl-1'-
piperidino)butyronitrile thus obtained melts at about 220.5-222°C. See
meperidine hydrochloride for synthesis of 4-phenyl-isonipecotic acid ethyl
ester.
brand name
Diarphem;Diarsed-neomycin;Diatro;Eldox;Logen;Lomanate;Lomax;Lomotil liquid;Lonox;Protector;Reasec;Saleton;Sedistal.
Therapeutic Function
Antidiarrheal
World Health Organization (WHO)
Diphenoxylate, a derivative of pethidine without analgesic activity, is used in the symptomatic treatment of acute and chronic diarrhoea to reduce intestinal motility. There is no clear evidence that it has any beneficial effect in diminishing fluid losses and it has been associated with central nervous system toxicity, particularly in children, which results in anorexia, nausea and vomiting, headache, drowsiness, confusion, insomnia, dizziness, restlessness, euphoria and depression. The World Health Organization recommends that diphenoxylate should not be used for the management of diarrhoea in children and many countries have since withdrawn products containing this compound indicated for paediatric use. (Reference: (WHORUD) The Rational Use of Drugs, , , 1990)
General Description
Diphenoxylate is a weak opioid agonist and isavailable combined with atropine (Lomotil) for use as an antidiarrhealagent. At low doses, the opioid effect is minimal,and the atropine is added to dissuade abuse. One studyfound both codeine and loperamide to be superior to diphenoxylatefor treating chronic diarrhea.83 The manufacturerhas strict dosing guidelines for pediatric use because opioidintoxication and deaths from diphenoxylate have beenreported.
Clinical Use
Lomotil is recommended as adjunctive therapy in the management of diarrhea. It is contraindicated in children under 2 years old and in patients with obstructive jaundice.
Side effects
Adverse reactions often caused by the atropine in the preparation include anorexia, nausea, pruritus, dizziness, and numbness of the extremities.
Synthesis
Diphenoxylate, ethyl ester of 1-(3-cyano-3,3-diphenylpropyl)- 4-phenylpiperidine-4-carboxylic acid (3.1.58), is also a drug of 4-phenylpiperidine series. In practice there are two ways of making it. The first way is by the alkylation of the ethyl ester of 4-phenylpiperidine-4-carboxylic acid (3.1.56) with 2,2-diphenyl-4-bromobutyronitrile, which in turn is synthesized from 1-benzyl-4-phenyl-4-cyanopiperidine. The product undergoes ethanolysis in the presence of acid, followed by benzylation. The second way is a synthesis accomplished by alkylation of diphenylacetonitrile using ethyl ester of 1-(2-chloroethyl)-4-phenylpiperidine-4-carboxylic acid (3.1.57), which is synthesized by reaction of ethyl ester of 4-phenylpiperidine-4-carboxylic acid with |?-chloroethanol or ethylenoxide with the subsequent substitution of hydroxyl group, which results from the opening of the epoxide ring, by chlorine via action of thionyl chloride [37,38].