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Identification
Name Diphenoxylate
Accession Number DB01081 (APRD00366)
Type small molecule
Groups illicit, approved
Description

A meperidine congener used as an antidiarrheal, usually in combination with atropine. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity. This medication is classified as a Schedule V under the Controlled Substances Act by the Food and Drug Administration (FDA) and the DEA in the United States when used in preparations. When diphenoxylate is used alone, it is classified as a Schedule II.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Dea No. 9170
  • Difenossilato [Dcit]
  • Difenoxilato [INN-Spanish]
  • Diphenoxalate
  • Diphenoxylate Hydrochloride
  • Diphenoxylatum [INN-Latin]
Synonyms
Dea No. 9170
Difenossilato [Dcit]
Difenoxilato [INN-Spanish]
Diphenoxalate
Diphenoxylate Hydrochloride
Diphenoxylatum [INN-Latin]
Salts Not Available
Brand names
Name Company
Lomotil
Brand mixtures
Brand Name Ingredients
Lomotil Atropine Sulfate + Diphenoxylate Hcl
Categories
  • Narcotics
  • Analgesics, Opioid
  • Antidiarrheals
  • Antiperistaltic
CAS number 915-30-0
Weight Average: 452.5873
Monoisotopic: 452.246378278
Chemical Formula C30H32N2O2
InChI Key InChIKey=HYPPXZBJBPSRLK-UHFFFAOYSA-N
InChI
InChI=1S/C30H32N2O2/c1-2-34-28(33)29(25-12-6-3-7-13-25)18-21-32(22-19-29)23-20-30(24-31,26-14-8-4-9-15-26)27-16-10-5-11-17-27/h3-17H,2,18-23H2,1H3
Plain Text
IUPAC Name
ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidine-4-carboxylate
SMILES
CCOC(=O)C1(CCN(CCC(C#N)(C2=CC=CC=C2)C2=CC=CC=C2)CC1)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpiperidines
  • Diphenylmethanes
Substructures
  • Carbonyl Compounds
  • Carboxylic Acids and Derivatives
  • Acetates
  • Phenylacetates
  • Nitriles and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Phenylpiperidines
  • Cyanides
  • Aliphatic and Aryl Amines
  • Diphenylmethanes
  • Heterocyclic compounds
  • Aromatic compounds
  • Phenylpropylamines
  • Piperidines
Pharmacology
Indication For as adjunctive therapy in the management of diarrhea
Pharmacodynamics Diphenoxylate, an antidiarrheal, is effective as adjunctive therapy in the management of diarrhea. Diphenoxylate is rapidly and extensively metabolized in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood.
Mechanism of action Diphenoxylate is an opiate receptor agonists that stimulate mu receptors in GI to decrease the peristalsis and constrict the sphincters. Diphenoxylate has a direct effect on circular smooth muscle of the bowel, that conceivably results in segmentation and prolongation of gastrointestinal transit time. The clinical antidiarrheal action of diphenoxylate may thus be a consequence of enhanced segmentation that allows increased contact of the intraluminal contents with the intestinal mucosa.
Absorption 90%
Volume of distribution Not Available
Protein binding 74-95%
Metabolism Hepatic
Route of elimination Not Available
Half life 12-14 hours
Clearance Not Available
Toxicity Coma, dry skin and mucous membranes, enlarged pupils of the eyes, extremely high body temperature, flushing, involuntary eyeball movement, lower than normal muscle tone, pinpoint pupils, rapid heartbeat, restlessness, sluggishness, suppressed breathing
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Solution Oral
Tablet Oral
Prices
Unit description Cost Unit
Lomotil 2.5-0.025 mg/5ml Liquid 60ml Bottle 30.86 USD bottle
Lomotil 2.5-0.025 mg tablet 1.4 USD tablet
Lomotil tablet 1.12 USD tablet
Patents Not Available
Properties
State solid
Melting point 221 oC
Experimental Properties
Property Value Source
water solubility 0.8 mg/ml PhysProp
logP 6.3 PhysProp
Predicted Properties
Property Value Source
water solubility 1.46e-03 g/l ALOGPS
logP 5.74 ALOGPS
logP 5.88 ChemAxon Molconvert
logS -5.5 ALOGPS
pKa 0 ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 53.33 ChemAxon Molconvert
rotatable bond count 9 ChemAxon Molconvert
refractivity 146.76 ChemAxon Molconvert
polarizability 51.58 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00301 Link_out
PubChem Compound 13505 Link_out
PubChem Substance 46507130 Link_out
ChemSpider 12919 Link_out
Therapeutic Targets Database DAP001136 Link_out
RxList http://www.rxlist.com/cgi/generic3/diphenoxylate.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Diphenoxylate Link_out
ATC Codes
  • A07DA01
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (49.7 KB)
Interactions
Drug Interactions
Drug Interaction
Donepezil Possible antagonism of action
Galantamine Possible antagonism of action
Food Interactions
  • Avoid alcohol.
  • Take with food.
Targets

1. Mu-type opioid receptor

Pharmacological action: yes
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin

Organism class: human
UniProt ID: P35372 Link_out
Gene: OPRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Baker DE: Loperamide: a pharmacological review. Rev Gastroenterol Disord. 2007;7 Suppl 3:S11-8. Pubmed
  3. Corazziari E: Role of opioid ligands in the irritable bowel syndrome. Can J Gastroenterol. 1999 Mar;13 Suppl A:71A-75A. Pubmed
  4. Coupar IM: The peristaltic reflex in the rat ileum: evidence for functional mu- and delta-opiate receptors. J Pharm Pharmacol. 1995 Aug;47(8):643-6. Pubmed
  5. De Luca A, Coupar IM: Difenoxin and loperamide: studies on possible mechanisms of intestinal antisecretory action. Naunyn Schmiedebergs Arch Pharmacol. 1993 Feb;347(2):231-7. Pubmed

2. Delta-type opioid receptor

Pharmacological action: unknown
Actions: agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins

Organism class: human
UniProt ID: P41143 Link_out
Gene: OPRD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Coupar IM: The peristaltic reflex in the rat ileum: evidence for functional mu- and delta-opiate receptors. J Pharm Pharmacol. 1995 Aug;47(8):643-6. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 14, 2012 11:45