Identification
- Summary
Dipivefrin is a prodrug of epinephrine used in ophthalmic solutions to reduce intraocular pressure in chronic open-angle glaucoma.
- Generic Name
- Dipivefrin
- DrugBank Accession Number
- DB00449
- Background
Dipivefrin is a prodrug of adrenaline, which is used to treat glaucoma. It is available as ophthalmic solution (eye drops).
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Dipivefrin (DB00449)
- Weight
- Average: 351.4373
Monoisotopic: 351.204573043 - Chemical Formula
- C19H29NO5
- Synonyms
- (±)-4-[1-hydroxy-2-(methylamino)ethyl]-o-phenylene divavalate
- 1-(3',4'-dipivaloyloxyphenyl)-2-methylamino-1-ethanol
- 4-[1-hydroxy-2-(methylamino)ethyl]-o-phenylene divavalate
- Dipivalyl epinephrine
- Dipivefrin
- Dipivefrina
- Dipivéfrine
- Dipivefrine
- Dipivefrinum
- External IDs
- DPE
- K 30081
Pharmacology
- Indication
Dipivefrin is a prodrug which is used as initial therapy for the control of intraocular pressure in chronic open-angle glaucoma.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Intraocular pressure •••••••••••• ••••••• ••••••••• •••••••• • ••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Dipivefrin is a member of a class of drugs known as prodrugs. Prodrugs are usually not active in themselves and require biotransformation to the parent compound before therapeutic activity is seen. These modifications are undertaken to enhance absorption, decrease side effects and enhance stability and comfort, thus making the parent compound a more useful drug. Enhanced absorption makes the prodrug a more efficient delivery system for the parent drug because less drug will be needed to produce the desired therapeutic response. Dipivefrin is a prodrug of epinephrine formed by the diesterification of epinephrine and pivalic acid. The addition of pivaloyl groups to the epinephrine molecule enhances its lipophilic character and, as a consequence, its penetration into the anterior chamber.
- Mechanism of action
Dipivefrin is a prodrug with little or no pharmacologically activity until it is hydrolyzed into epinephrine inside the human eye. The liberated epinephrine, an adrenergic agonist, appears to exert its action by stimulating α -and/or β2-adrenergic receptors, leading to a decrease in aqueous production and an enhancement of outflow facility. The dipivefrin prodrug delivery system is a more efficient way of delivering the therapeutic effects of epinephrine, with fewer side effects than are associated with conventional epinephrine therapy.
Target Actions Organism AAlpha-1A adrenergic receptor agonistHumans AAlpha-2A adrenergic receptor agonistHumans ABeta-2 adrenergic receptor agonistHumans ACholinesterase substrateHumans UAcetylcholinesterase inhibitorHumans - Absorption
Well absorbed following occular administration.
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Dipivefrin is converted to epinephrine inside the human eye by enzyme hydrolysis.
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Oral LD50 in rat is 183 mg/kg.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 softwareAminophylline The risk or severity of hypokalemia can be increased when Aminophylline is combined with Dipivefrin. Bendroflumethiazide The risk or severity of hypokalemia can be increased when Dipivefrin is combined with Bendroflumethiazide. Benzthiazide The risk or severity of hypokalemia can be increased when Dipivefrin is combined with Benzthiazide. Bromotheophylline The risk or severity of hypokalemia can be increased when Bromotheophylline is combined with Dipivefrin. Caffeine The risk or severity of hypokalemia can be increased when Caffeine is combined with Dipivefrin. - Food Interactions
- No interactions found.
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 Dipivefrin hydrochloride 5QTH9UHV0K 64019-93-8 VKFAUCPBMAGVRG-UHFFFAOYSA-N - International/Other Brands
- AKPro (Akorn) / D Epifrin (Allergan) / Diopine (Allergan) / Pivalephrine (Santen Pharmaceutical) / Pro-Epinephrine / Thilodrin (Alcon)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Dipivefrin-liq Oph 0.1% Liquid .1 % Ophthalmic Alcon, Inc. 1995-12-31 1996-08-16 Canada 
Dpe Ophthalmic Solution - 0.1% Solution / drops .1 % Ophthalmic; Topical Alcon, Inc. 1995-12-31 1999-12-23 Canada Propine Solution / drops 1 mg/1mL Ophthalmic Allergan 2001-09-04 2010-01-04 US 
Propine Liq 0.1% Liquid 1 mg / mL Ophthalmic Allergan 1981-12-31 2011-08-04 Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-dipivefrin Liquid 0.1 % Ophthalmic Apotex Corporation 2000-07-17 2022-03-11 Canada Dipivefrin Hydrochloride Solution 1 mg/1mL Ophthalmic Sandoz Inc. 1994-06-30 2004-12-31 US Dipivefrin Hydrochloride Solution / drops 1 mg/1mL Ophthalmic Bauch & Lomb Incorporated 1995-05-19 2007-12-01 US PMS-dipivefrin Solution / drops 0.1 % Ophthalmic Pharmascience Inc 1998-08-31 2016-10-28 Canada Ratio-dipivefrin Solution 0.1 % Ophthalmic Ratiopharm Inc Division Of Teva Canada Limited 1995-12-31 2006-08-04 Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Probeta - Liq Oph Dipivefrin hydrochloride (0.1 %) + Levobunolol hydrochloride (0.5 %) Liquid Ophthalmic Allergan 1996-08-30 2012-07-16 Canada
Categories
- ATC Codes
- S01EA02 — Dipivefrine
- Drug Categories
- Adrenergic Agents
- Adrenergic Agonists
- Adrenergic alpha-1 Receptor Agonists
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Adrenergic beta-1 Receptor Agonists
- Adrenergic beta-2 Receptor Agonists
- Adrenergic beta-3 Receptor Agonists
- Adrenergic beta-Agonists
- Alcohols
- Amines
- Amino Alcohols
- Antiglaucoma Preparations and Miotics
- Benzene Derivatives
- Biogenic Amines
- Biogenic Monoamines
- Catecholamines
- Catechols
- Cholinesterase substrates
- Ethanolamines
- Mydriatics
- Neurotransmitter Agents
- Ophthalmics
- Ophthalmologicals
- Phenols
- Sensory Organs
- Sympathomimetics in Glaucoma Therapy
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenol esters. These are aromatic compounds containing a benzene ring substituted by a hydroxyl group and an ester group.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Phenol esters
- Sub Class
- Not Available
- Direct Parent
- Phenol esters
- Alternative Parents
- Phenoxy compounds / Aralkylamines / Dicarboxylic acids and derivatives / Secondary alcohols / Carboxylic acid esters / Amino acids and derivatives / 1,2-aminoalcohols / Dialkylamines / Organopnictogen compounds / Organic oxides show 3 more
- Substituents
- 1,2-aminoalcohol / Alcohol / Amine / Amino acid or derivatives / Aralkylamine / Aromatic alcohol / Aromatic homomonocyclic compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester show 14 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- ethanolamines, pivalate ester (CHEBI:4646)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 8Q1PVL543G
- CAS number
- 52365-63-6
- InChI Key
- OCUJLLGVOUDECM-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H29NO5/c1-18(2,3)16(22)24-14-9-8-12(13(21)11-20-7)10-15(14)25-17(23)19(4,5)6/h8-10,13,20-21H,11H2,1-7H3
- IUPAC Name
- 2-[(2,2-dimethylpropanoyl)oxy]-5-[1-hydroxy-2-(methylamino)ethyl]phenyl 2,2-dimethylpropanoate
- SMILES
- CNCC(O)C1=CC(OC(=O)C(C)(C)C)=C(OC(=O)C(C)(C)C)C=C1
References
- Synthesis Reference
Hussain, A. and Truelove, J.E.; U.S. Patents 3,809.714; May 7,1974; and 3,839,584; October 1, 1974; both assigned to Inter Rx Research Corp. Henschler, D., Wagner, J. and Hampel, H.; US. Patent 4,085,270; April 18,1978; assigned to Chemisch-Pharmazeutische Fabrik Adolf Klinge & Co. (W. Germany).
- General References
- FDA Approved Drug Products: PROPINE (dipivefrin hydrochloride) solution [Link]
- External Links
- Human Metabolome Database
- HMDB0014592
- KEGG Drug
- D02349
- KEGG Compound
- C06963
- PubChem Compound
- 3105
- PubChem Substance
- 46504716
- ChemSpider
- 2994
- 23410
- ChEBI
- 4646
- ChEMBL
- CHEMBL1201262
- Therapeutic Targets Database
- DAP000593
- PharmGKB
- PA449364
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Dipivefrine
- FDA label
- Download (60.3 KB)
- MSDS
- Download (50.2 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
Pharmacoeconomics
- Manufacturers
- Akorn inc
- Bausch and lomb pharmaceuticals inc
- Falcon pharmaceuticals ltd
- Allergan pharmaceutical
- Packagers
- Allergan Inc.
- Dispensing Solutions
- Pacific Pharma Lp
- Pharmedix
- Physicians Total Care Inc.
- Taylor Pharmaceuticals
- Dosage Forms
Form Route Strength Liquid Ophthalmic 0.1 % Solution Ophthalmic 1 mg/1mL Solution / drops Ophthalmic 1 mg/1mL Liquid Ophthalmic .1 % Solution / drops Ophthalmic; Topical .1 % Solution / drops Ophthalmic 0.1 % Liquid Ophthalmic Solution / drops Ophthalmic Liquid Ophthalmic 1 mg / mL Solution Ophthalmic 0.1 % - Prices
Unit description Cost Unit Propine 0.1% eye drops 5.02USD ml 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) 146-147 Hussain, A. and Truelove, J.E.; U.S. Patents 3,809.714; May 7,1974; and 3,839,584; October 1, 1974; both assigned to Inter Rx Research Corp. Henschler, D., Wagner, J. and Hampel, H.; US. Patent 4,085,270; April 18,1978; assigned to Chemisch-Pharmazeutische Fabrik Adolf Klinge & Co. (W. Germany). water solubility Freely soluble as HCl salt Not Available logP 1.7 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0582 mg/mL ALOGPS logP 3.17 ALOGPS logP 3.71 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 14 Chemaxon pKa (Strongest Basic) 9.33 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 84.86 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 94.94 m3·mol-1 Chemaxon Polarizability 39.33 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.8575 Blood Brain Barrier - 0.9747 Caco-2 permeable - 0.7458 P-glycoprotein substrate Substrate 0.7499 P-glycoprotein inhibitor I Non-inhibitor 0.6617 P-glycoprotein inhibitor II Non-inhibitor 0.7348 Renal organic cation transporter Non-inhibitor 0.9396 CYP450 2C9 substrate Non-substrate 0.8238 CYP450 2D6 substrate Non-substrate 0.8369 CYP450 3A4 substrate Non-substrate 0.5056 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9129 CYP450 3A4 inhibitor Non-inhibitor 0.5546 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9757 Ames test Non AMES toxic 0.9063 Carcinogenicity Non-carcinogens 0.8624 Biodegradation Not ready biodegradable 0.7095 Rat acute toxicity 2.2818 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9635 hERG inhibition (predictor II) Non-inhibitor 0.8847
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-052f-9150000000-30a32fb00720193ce912 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0ue9-0019000000-9b25b34c56055e331b71 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-0129000000-0e00d44898c55e842794 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0ue9-1069000000-369262f75e5375cab111 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-1794000000-0c20c2ea5acb3fc25924 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-5092000000-ff4e56157ddceff0e07d Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0079-3291000000-fb767417ae70e64257cc Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 203.3527354 predictedDarkChem Lite v0.1.0 [M-H]- 188.77998 predictedDeepCCS 1.0 (2019) [M+H]+ 203.6900354 predictedDarkChem Lite v0.1.0 [M+H]+ 191.3637 predictedDeepCCS 1.0 (2019) [M+Na]+ 203.8397354 predictedDarkChem Lite v0.1.0 [M+Na]+ 198.85207 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Protein heterodimerization activity
- Specific Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
- Gene Name
- ADRA1A
- Uniprot ID
- P35348
- Uniprot Name
- Alpha-1A adrenergic receptor
- Molecular Weight
- 51486.005 Da
References
- Sanbe A, Tanaka Y, Fujiwara Y, Tsumura H, Yamauchi J, Cotecchia S, Koike K, Tsujimoto G, Tanoue A: Alpha1-adrenoceptors are required for normal male sexual function. Br J Pharmacol. 2007 Oct;152(3):332-40. Epub 2007 Jul 2. [Article]
- Tomiyama Y, Kobayashi K, Tadachi M, Kobayashi S, Inada Y, Kobayashi M, Yamazaki Y: Expressions and mechanical functions of alpha1-adrenoceptor subtypes in hamster ureter. Eur J Pharmacol. 2007 Nov 14;573(1-3):201-5. Epub 2007 Jul 6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Thioesterase binding
- Specific Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
- Gene Name
- ADRA2A
- Uniprot ID
- P08913
- Uniprot Name
- Alpha-2A adrenergic receptor
- Molecular Weight
- 48956.275 Da
References
- Arthur S, Cantor LB: Update on the role of alpha-agonists in glaucoma management. Exp Eye Res. 2011 Sep;93(3):271-83. doi: 10.1016/j.exer.2011.04.002. Epub 2011 Apr 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Protein homodimerization activity
- Specific Function
- Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
- Gene Name
- ADRB2
- Uniprot ID
- P07550
- Uniprot Name
- Beta-2 adrenergic receptor
- Molecular Weight
- 46458.32 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Ozakca I, Arioglu E, Guner S, Altan VM, Ozcelikay AT: Role of beta-3-adrenoceptor in catecholamine-induced relaxations in gastric fundus from control and diabetic rats. Pharmacology. 2007;80(4):227-38. Epub 2007 Jul 6. [Article]
- Prenner L, Sieben A, Zeller K, Weiser D, Haberlein H: Reduction of high-affinity beta2-adrenergic receptor binding by hyperforin and hyperoside on rat C6 glioblastoma cells measured by fluorescence correlation spectroscopy. Biochemistry. 2007 May 1;46(17):5106-13. Epub 2007 Apr 7. [Article]
- Lucin KM, Sanders VM, Jones TB, Malarkey WB, Popovich PG: Impaired antibody synthesis after spinal cord injury is level dependent and is due to sympathetic nervous system dysregulation. Exp Neurol. 2007 Sep;207(1):75-84. Epub 2007 Jun 2. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Substrate
- General Function
- Identical protein binding
- Specific Function
- Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
- Gene Name
- BCHE
- Uniprot ID
- P06276
- Uniprot Name
- Cholinesterase
- Molecular Weight
- 68417.575 Da
References
- Nakamura M, Shirasawa E, Hikida M: Characterization of esterases involved in the hydrolysis of dipivefrin hydrochloride. Ophthalmic Res. 1993;25(1):46-51. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Serine hydrolase activity
- Specific Function
- Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
- Gene Name
- ACHE
- Uniprot ID
- P22303
- Uniprot Name
- Acetylcholinesterase
- Molecular Weight
- 67795.525 Da
References
- Nakamura M, Shirasawa E, Hikida M: Characterization of esterases involved in the hydrolysis of dipivefrin hydrochloride. Ophthalmic Res. 1993;25(1):46-51. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55