Diphenoxylate
Identification
- Summary
Diphenoxylate is an antidiarrheal medication used with atropine to manage diarrhea.
- Brand Names
- Lomotil
- Generic Name
- Diphenoxylate
- DrugBank Accession Number
- DB01081
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Illicit
- Structure
Structure for Diphenoxylate (DB01081)
- Weight
- Average: 452.5873
Monoisotopic: 452.246378278 - Chemical Formula
- C30H32N2O2
- Synonyms
- 1-(3-Cyano-3,3-diphenylpropyl)-4-phenyl-isonipecotic acid ethyl ester
- 2,2-Diphenyl-4-(4-carbethoxy-4-phenylpiperidino)butyronitrile
- Difenossilato
- Difenoxilato
- Diphenoxylate
- Diphenoxylatum
- Ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylate
- Ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotate
- External IDs
- DEA No. 9170
- IDS-ND-016
- R-1132
Pharmacology
- Indication
For as adjunctive therapy in the management of diarrhea
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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.
Target Actions Organism AMu-type opioid receptor agonistHumans UDelta-type opioid receptor agonistHumans - 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
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- 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
- Pathways
Pathway Category Diphenoxylate Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Diphenoxylate is combined with 1,2-Benzodiazepine. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Diphenoxylate. Acetophenazine The risk or severity of hypotension and CNS depression can be increased when Acetophenazine is combined with Diphenoxylate. Aclidinium The risk or severity of adverse effects can be increased when Aclidinium is combined with Diphenoxylate. Agomelatine The risk or severity of adverse effects can be increased when Diphenoxylate is combined with Agomelatine. Alfentanil The risk or severity of adverse effects can be increased when Alfentanil is combined with Diphenoxylate. Alimemazine The risk or severity of hypotension and CNS depression can be increased when Alimemazine is combined with Diphenoxylate. Alloin The therapeutic efficacy of Alloin can be decreased when used in combination with Diphenoxylate. Almotriptan The risk or severity of adverse effects can be increased when Almotriptan is combined with Diphenoxylate. Alosetron The risk or severity of adverse effects can be increased when Alosetron is combined with Diphenoxylate. 
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- Avoid alcohol.
- Take with food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Diphenoxylate hydrochloride W24OD7YW48 3810-80-8 SHTAFWKOISOCBI-UHFFFAOYSA-N - Product Images
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Diphenoxylate Hcl and Atropine Sulfate Diphenoxylate hydrochloride (2.5 mg/1) + Atropine sulfate anyhdrous (0.025 mg/1) Tablet Oral Stat Rx USA 1979-10-29 Not applicable US 
Diphenoxylate Hydrochloride and Atropine Sulfate Diphenoxylate hydrochloride (2.5 mg/1) + Atropine sulfate anyhdrous (0.025 mg/1) Tablet Oral A-S Medication Solutions 1977-11-17 Not applicable US 
Diphenoxylate Hydrochloride and Atropine Sulfate Diphenoxylate (2.5 mg/1) + Atropine (0.025 mg/1) Tablet Oral RedPharm Drug, Inc. 2019-01-01 Not applicable US Diphenoxylate Hydrochloride and Atropine Sulfate Diphenoxylate hydrochloride (2.5 mg/1) + Atropine sulfate anyhdrous (0.025 mg/1) Tablet Oral Aphena Pharma Solutions Tennessee, Inc. 2017-06-20 Not applicable US Diphenoxylate Hydrochloride and Atropine Sulfate Diphenoxylate hydrochloride (2.5 mg/1) + Atropine sulfate anyhdrous (0.025 mg/1) Tablet Oral KAISER FOUNDATION HOSPITALS 2010-11-30 2017-08-31 US Diphenoxylate Hydrochloride and Atropine Sulfate Diphenoxylate hydrochloride (2.5 mg/1) + Atropine sulfate anyhdrous (0.025 mg/1) Tablet Oral Preferred Pharmaceuticals, Inc. 1977-11-17 2019-08-27 US 
Diphenoxylate Hydrochloride and Atropine Sulfate Diphenoxylate hydrochloride (2.5 mg/1) + Atropine sulfate anyhdrous (0.025 mg/1) Tablet Oral Mylan Pharmaceuticals Inc. 1977-11-17 Not applicable US 
Diphenoxylate Hydrochloride and Atropine Sulfate Diphenoxylate hydrochloride (2.5 mg/1) + Atropine sulfate anyhdrous (0.025 mg/1) Tablet Oral Apotheca, Inc. 1977-11-17 Not applicable US Diphenoxylate hydrochloride and atropine sulfate Diphenoxylate hydrochloride (2.5 mg/1) + Atropine sulfate (0.025 mg/1) Tablet Oral Aphena Pharma Solutions - Tennessee, LLC 2018-08-31 Not applicable US Diphenoxylate Hydrochloride and Atropine Sulfate Diphenoxylate hydrochloride (2.5 mg/1) + Atropine sulfate (0.025 mg/1) Tablet Oral bryant ranch prepack 2017-07-07 Not applicable US
Categories
- ATC Codes
- A07DA01 — Diphenoxylate
- Drug Categories
- Alimentary Tract and Metabolism
- Analgesics
- Antidiarrheals
- Antidiarrheals, Intestinal Antiinflammatory/antiinfective Agents
- Antipropulsives
- Central Nervous System Agents
- Central Nervous System Depressants
- Gastrointestinal Agents
- Isonipecotic Acids
- Opioids
- Peripheral Nervous System Agents
- Piperidines
- Sensory System Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylacetonitriles. These are cyclic aromatic compounds containing a diphenylacetonitrile moiety, which consists of a diphenylmethane linked to and acetonitrile to form 2,2-diphenylacetonitrile.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylacetonitriles
- Direct Parent
- Diphenylacetonitriles
- Alternative Parents
- Diphenylmethanes / Phenylpiperidines / Piperidinecarboxylic acids / Aralkylamines / Trialkylamines / Carboxylic acid esters / Amino acids and derivatives / Nitriles / Monocarboxylic acids and derivatives / Azacyclic compounds show 4 more
- Substituents
- Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Carbonitrile / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Diphenylacetonitrile show 16 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- ethyl ester, tertiary amine, nitrile, piperidinecarboxylate ester (CHEBI:4639)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 73312P173G
- CAS number
- 915-30-0
- InChI Key
- 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
- 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
References
- Synthesis Reference
Janssen, P.A.J.; U.S.Patent 2,898,340; August 4,1959. Dryden, H.L. Jr. and Erickson, R.A.; U.S. Patent 4,086,234; April 25,1978; assigned to G.D.Searle & Co.
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015213
- KEGG Drug
- D00301
- KEGG Compound
- C07872
- PubChem Compound
- 13505
- PubChem Substance
- 46507130
- ChemSpider
- 12919
- BindingDB
- 50401672
- 3500
- ChEBI
- 4639
- ChEMBL
- CHEMBL1201294
- ZINC
- ZINC000003830716
- Therapeutic Targets Database
- DAP001136
- PharmGKB
- PA164746539
- RxList
- RxList Drug Page
- Wikipedia
- Diphenoxylate
- MSDS
- Download (49.7 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Completed Diagnostic Malignant Lymphomas 1 2 Recruiting Treatment Breast Adenocarcinoma / HER2/Neu-positive Breast Cancer / Stage II Breast Cancer AJCC v6 and v7 / Stage IIA Breast Cancer AJCC v6 and v7 / Stage IIB Breast Cancer AJCC v6 and v7 / Stage III Breast Cancer AJCC V7 / Stage IIIA Breast Cancer AJCC v7 / Stage IIIB Breast Cancer AJCC v7 / Stage IIIC Breast Cancer AJCC v7 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Amerisource Health Services Corp.
- Amneal Pharmaceuticals
- A-S Medication Solutions LLC
- Bryant Ranch Prepack
- Cardinal Health
- Caremark LLC
- Comprehensive Consultant Services Inc.
- Direct Dispensing Inc.
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Eon Labs
- GD Searle LLC
- Group Health Cooperative
- H.J. Harkins Co. Inc.
- Heartland Repack Services LLC
- Ivax Pharmaceuticals
- Kaiser Foundation Hospital
- Keltman Pharmaceuticals Inc.
- Lake Erie Medical and Surgical Supply
- Lannett Co. Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Nucare Pharmaceuticals Inc.
- Palmetto Pharmaceuticals Inc.
- Patient First Corp.
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Pharmacia Inc.
- Pharmedix
- Physicians Total Care Inc.
- Preferred Pharmaceuticals Inc.
- Prepackage Specialists
- Prepak Systems Inc.
- Rebel Distributors Corp.
- Redpharm Drug
- Remedy Repack
- Roxane Labs
- Sandhills Packaging Inc.
- Sandoz
- St Mary's Medical Park Pharmacy
- UDL Laboratories
- Va Cmop Dallas
- Dosage Forms
Form Route Strength Solution Oral Tablet Oral 2.5 mg Liquid Oral Tablet Oral Tablet - Prices
Unit description Cost Unit Lomotil 2.5-0.025 mg/5ml Liquid 60ml Bottle 30.86USD bottle Lomotil 2.5-0.025 mg tablet 1.4USD tablet Lomotil tablet 1.12USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 220.5-222 Janssen, P.A.J.; U.S.Patent 2,898,340; August 4,1959. Dryden, H.L. Jr. and Erickson, R.A.; U.S. Patent 4,086,234; April 25,1978; assigned to G.D.Searle & Co. water solubility 800 mg/L (at 25 °C) MERCK INDEX (1996) logP 6.3 Not Available - Predicted Properties
Property Value Source Water Solubility 0.00146 mg/mL ALOGPS logP 5.74 ALOGPS logP 5.88 ChemAxon logS -5.5 ALOGPS pKa (Strongest Basic) 8.5 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 53.33 Å2 ChemAxon Rotatable Bond Count 9 ChemAxon Refractivity 146.76 m3·mol-1 ChemAxon Polarizability 51.58 Å3 ChemAxon Number of Rings 4 ChemAxon Bioavailability 1 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9903 Blood Brain Barrier + 0.9592 Caco-2 permeable + 0.5316 P-glycoprotein substrate Substrate 0.7094 P-glycoprotein inhibitor I Inhibitor 0.7045 P-glycoprotein inhibitor II Inhibitor 0.7845 Renal organic cation transporter Inhibitor 0.5967 CYP450 2C9 substrate Non-substrate 0.8333 CYP450 2D6 substrate Non-substrate 0.5667 CYP450 3A4 substrate Non-substrate 0.5988 CYP450 1A2 substrate Non-inhibitor 0.6827 CYP450 2C9 inhibitor Inhibitor 0.6701 CYP450 2D6 inhibitor Inhibitor 0.6461 CYP450 2C19 inhibitor Inhibitor 0.51 CYP450 3A4 inhibitor Inhibitor 0.5797 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.817 Ames test Non AMES toxic 0.8482 Carcinogenicity Non-carcinogens 0.839 Biodegradation Not ready biodegradable 0.9805 Rat acute toxicity 3.3423 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7969 hERG inhibition (predictor II) Inhibitor 0.592
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Voltage-gated calcium channel activity
- Specific Function
- Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
- Gene Name
- OPRM1
- Uniprot ID
- P35372
- Uniprot Name
- Mu-type opioid receptor
- Molecular Weight
- 44778.855 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Baker DE: Loperamide: a pharmacological review. Rev Gastroenterol Disord. 2007;7 Suppl 3:S11-8. [Article]
- Corazziari E: Role of opioid ligands in the irritable bowel syndrome. Can J Gastroenterol. 1999 Mar;13 Suppl A:71A-75A. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Opioid receptor activity
- Specific Function
- G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
- Gene Name
- OPRD1
- Uniprot ID
- P41143
- Uniprot Name
- Delta-type opioid receptor
- Molecular Weight
- 40368.235 Da
References
- 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. [Article]
Drug created on June 13, 2005 13:24 / Updated on August 07, 2021 00:40