DIPIVEFRIN

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C19H29NO5
Molecular Weight	351.4373
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNCC(O)C1=CC(OC(=O)C(C)(C)C)=C(OC(=O)C(C)(C)C)C=C1

InChI

InChIKey=OCUJLLGVOUDECM-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00449
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/18239s25lbl.pdf

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. Dipivefrin is used as initial therapy for the control of intraocular pressure in chronic open-angle glaucoma.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Alpha-1a adrenergic receptor 66 Target ID: CHEMBL229 Sources: http://www.drugbank.ca/drugs/DB00449	Agonist 2678
Alpha-2a adrenergic receptor 63 Target ID: CHEMBL1867 Sources: http://www.drugbank.ca/drugs/DB00449	Agonist 2678
Beta-2 adrenergic receptor 203 Target ID: CHEMBL210 Sources: http://www.drugbank.ca/drugs/DB00449	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic open-angle glaucoma 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/18239s25lbl.pdf	Primary		Approved 8429	PROPINE Approved Use PROPINE (dipivefrin HCI ophthalmic solution, USP) is indicated as initial therapy for the control of intraocular pressure in chronic open-angle glaucoma. Launch Date 1980

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
carboxylesterase 2	ACHE 10 carboxylesterase 4 non-specific esterase 2

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
carboxylesterase 2	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/8446367/ Page: -	yes [IC50 3000 uM]

Drug as victim

Target	Modality	Activity
carboxylesterase 4	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8446367/ Page: -	yes [Km 1030 uM]
ACHE 10	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8446367/ Page: -	yes [Km 1410 uM]
non-specific esterase 2	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8446367/ Page: -	yes [Km 2160 uM]

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4646	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4646
ChemicalBook	CB6676807	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6676807

PubMed

Title	Date	PubMed
External ocular toxicity of dipivalyl epinephrine.	1979 Dec	517603
Experience with dipivalyl epinephrine. Its effectiveness, alone or in combination, and its side effects.	1983 Aug	6639507
Systemic hypertension in patients receiving dipivalyl adrenaline for glaucoma.	1988 Sep 17	3147756
Central vein thrombosis and topical dipivalyl epinephrine.	1990 Aug	2220369
Corneal vascularization and opacification during long-term use of dipivefrin.	1995 Spring	8535955
Effects of latanoprost and dipivefrin, alone or combined, on intraocular pressure and on blood-aqueous barrier permeability.	1998 Apr	9640189
[Effects of ocular hypotensive agents on the circadian rhythm in intraocular pressure in rabbits as measured by telemetry].	2003 Sep	14531310
Contact dermatitis by dipivefrine.	2005 Mar	15811042
Glaucoma alters the circadian timing system.	2008	19079596
Pupillary supersensitivity and visual disturbance in Parkinson's disease.	2008 Feb	18265941
Comparison of chiral electrophoretic separation methods for phenethylamines and application on impurity analysis.	2010 Dec 15	20638811
Pupillary autonomic dysfunction in multiple system atrophy and Parkinson's disease: an assessment by eye-drop tests.	2010 Jun	20127386

Patents

Sample Use Guides

In Vivo Use Guide

Initial Glaucoma Therapy The usual dosage of Dipivefrin Hydrochloride Ophthalmic Solution 0.1% is one drop in the eye(s) every 12 hours.

Route of Administration: Irrigation

In Vitro Use Guide

Dipivefrin caused a reduction in bovine trabecular cell density at concentration 103-260 uM

Name

Type

Language

DIPIVEFRIN

Official Name

English

Dipivefrine [WHO-DD]

Common Name

English

dipivefrine [INN]

Common Name

English

DIPIVEFRINE

Official Name

English

DIPIVALYL EPINEPHRINE

Common Name

English

PROPANOIC ACID, 2,2-DIMETHYL-, 4-(1-HYDROXY-2-(METHYLAMINO)ETHYL)-1,2-PHENYLENE ESTER, (±)-

Common Name

English

DIPIVEFRIN [VANDF]

Common Name

English

DIPIVEFRIN [MI]

Common Name

English

DIPIVEFRINE [MART.]

Common Name

English

DIPIVEFRIN [USAN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

S01EA02