Details of the Drug

General Information of Drug (ID: DMH5W0G)

• Drug Name: Dipivefrin
• Synonyms: AKPro; Dipivefrina; Dipivefrine; Dipivefrinum; Propine; Dipivalyl epinephrine; Dipivefrin HCL; Dipivefrin [USAN]; K 30081; Dipivefrin (USAN); Dipivefrina [INN-Spanish]; Dipivefrine (INN); Dipivefrinum [INN-Latin]; Ophtho-Dipivefrin; Propine C Cap B.I.D.; [2-(2,2-dimethylpropanoyloxy)-4-[1-hydroxy-2-(methylamino)ethyl]phenyl] 2,2-dimethylpropanoate; (+-)-3,4-Dihydroxy-alpha-((methylamino)methyl)benzyl alcohol 3,4-dipivalate; (+-)-4-[1-hydroxy-2-(methylamino)ethyl]-o-phenylene divavalate; (-)-2,2-Dimethylpropansaeure-4-(1-hydroxy-2-(methylamino)ethyl)-1,2-phenylenester; (-)-4-(1-Hydroxy-2-methylaminoethyl)-o-phenylendipivalat; (RS)-4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-phenylen dipivalat; 1-(3',4'-dipivaloyloxyphenyl)-2-methylamino-1-ethanol; 2,2-Dimethylpropanoic acid 4-[1-hydroxy-2-(methylamino)ethyl]-1,2-phenylene ester; 4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-phenylen dipivalat; 4-[1-hydroxy-2-(methylamino)ethyl]-o-phenylene divavalate; 4-[1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diyl bis(2,2-dimethylpropanoate)

Indication

Disease Entry	ICD 11	Status	REF
Chronic open-angle glaucoma	9C61.0	Approved	[1]

• Therapeutic Class: Ophthalmologicals
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 351.4
  Topological Polar Surface Area (xlogp); 2.9
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 6
• ADMET Property:
  Absorption: The drug is well absorbed after occular administration [2]
  Metabolism: The drug is metabolized via the enzyme hydrolysis [2]
• Chemical Identifiers:
  Formula: C19H29NO5
  IUPAC Name: [2-(2,2-dimethylpropanoyloxy)-4-[1-hydroxy-2-(methylamino)ethyl]phenyl] 2,2-dimethylpropanoate
  Canonical SMILES: CC(C)(C)C(=O)OC1=C(C=C(C=C1)C(CNC)O)OC(=O)C(C)(C)C
  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
  InChIKey: OCUJLLGVOUDECM-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3105
  ChEBI ID: CHEBI:4646
  CAS Number: 52365-63-6
  DrugBank ID: DB00449
  TTD ID: D01JFT
  ACDINA ID: D01008

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Adrenergic receptor beta-1 (ADRB1)	TTR6W5O	ADRB1_HUMAN	Antagonist	[3]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Dipivefrin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Methylene blue	DMJAPE7	Moderate	Decreased metabolism of Dipivefrin caused by Methylene blue mediated inhibition of non-CYP450 enzyme.	Acquired methaemoglobinaemia [3A93]	[12]
Linezolid	DMGFPU2	Moderate	Decreased metabolism of Dipivefrin caused by Linezolid mediated inhibition of non-CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[12]
Levomilnacipran	DMV26S8	Moderate	Additive hypertensive effects by the combination of Dipivefrin and Levomilnacipran.	Chronic pain [MG30]	[13]
Selegiline	DM6034S	Moderate	Decreased metabolism of Dipivefrin caused by Selegiline mediated inhibition of non-CYP450 enzyme.	Depression [6A70-6A7Z]	[12]
Duloxetine	DM9BI7M	Moderate	Increased risk of rapid heart rate by the combination of Dipivefrin and Duloxetine.	Depression [6A70-6A7Z]	[13]
Isocarboxazid	DMAF1NB	Moderate	Decreased metabolism of Dipivefrin caused by Isocarboxazid mediated inhibition of non-CYP450 enzyme.	Depression [6A70-6A7Z]	[12]
Milnacipran	DMBFE74	Moderate	Additive hypertensive effects by the combination of Dipivefrin and Milnacipran.	Depression [6A70-6A7Z]	[13]
Tranylcypromine	DMGB5RE	Moderate	Decreased metabolism of Dipivefrin caused by Tranylcypromine mediated inhibition of non-CYP450 enzyme.	Depression [6A70-6A7Z]	[12]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of rapid heart rate by the combination of Dipivefrin and Desvenlafaxine.	Depression [6A70-6A7Z]	[13]
Phenelzine	DMHIDUE	Moderate	Decreased metabolism of Dipivefrin caused by Phenelzine mediated inhibition of non-CYP450 enzyme.	Depression [6A70-6A7Z]	[12]
Ergotamine	DMKR3C5	Major	Additive hypertensive effects by the combination of Dipivefrin and Ergotamine.	Headache [8A80-8A84]	[14]
Procarbazine	DMIK367	Moderate	Decreased metabolism of Dipivefrin caused by Procarbazine mediated inhibition of non-CYP450 enzyme.	Hodgkin lymphoma [2B30]	[12]
Ozanimod	DMT6AM2	Moderate	Decreased metabolism of Dipivefrin caused by Ozanimod mediated inhibition of non-CYP450 enzyme.	Multiple sclerosis [8A40]	[12]
Sibutramine	DMFJTDI	Moderate	Increased risk of rapid heart rate by the combination of Dipivefrin and Sibutramine.	Obesity [5B80-5B81]	[15]
Safinamide	DM0YWJC	Moderate	Decreased metabolism of Dipivefrin caused by Safinamide mediated inhibition of non-CYP450 enzyme.	Parkinsonism [8A00]	[12]
Rasagiline	DM3WKQ4	Moderate	Decreased metabolism of Dipivefrin caused by Rasagiline mediated inhibition of non-CYP450 enzyme.	Parkinsonism [8A00]	[12]
Ergonovine	DM0VEC1	Major	Additive hypertensive effects by the combination of Dipivefrin and Ergonovine.	Postpartum haemorrhage [JA43]	[14]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Hydrochloric acid	E00015	313	Acidulant
Benzalkonium chloride	E00536	21988052	Antimicrobial preservative; Penetration agent; Solubilizing agent; Surfactant
Edetate disodium	E00186	8759	Complexing agent
Sodium chloride	E00077	5234	Diluent; Tonicity agent
Water	E00035	962	Solvent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Dipivefrin 0.1% solution	0.10%	Solution	Ophthalmic

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [3] Contractile response of the isolated trabecular meshwork and ciliary muscle to cholinergic and adrenergic agents. Ger J Ophthalmol. 1996 May;5(3):146-53.
• [4] Beta-blockers in the treatment of hypertension: are there clinically relevant differences Postgrad Med. 2009 May;121(3):90-8.
• [5] Adrenergic activation of electrogenic K+ secretion in guinea pig distal colonic epithelium: involvement of beta1- and beta2-adrenergic receptors. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G269-77.
• [6] Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med. 1999 Feb;27(2):325-31.
• [7] Prediction and experimental validation of acute toxicity of beta-blockers in Ceriodaphnia dubia. Environ Toxicol Chem. 2005 Oct;24(10):2470-6.
• [8] Topical dorzolamide 2%/timolol 0.5% ophthalmic solution: a review of its use in the treatment of glaucoma and ocular hypertension. Drugs Aging. 2006;23(12):977-95.
• [9] Current therapeutic uses and potential of beta-adrenoceptor agonists and antagonists. Eur J Clin Pharmacol. 1998 Feb;53(6):389-404.
• [10] beta-adrenergic enhancement of brain kynurenic acid production mediated via cAMP-related protein kinase A signaling. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Apr 30;33(3):519-29.
• [11] beta(2)-adrenoceptors are critical for antidepressant treatment of neuropathic pain. Ann Neurol. 2009 Feb;65(2):218-25.
• [12] Cusson JR, Goldenberg E, Larochelle P "Effect of a novel monoamine-oxidase inhibitor, moclobemide on the sensitivity to intravenous tyramine and norepinephrine in humans." J Clin Pharmacol 31 (1991): 462-7. [PMID: 2050833]
• [13] Product Information. Cymbalta (duloxetine). Lilly, Eli and Company, Indianapolis, IN.
• [14] Barthel W, Glusa E, Koth W "Interactions of dihydroergotamine with etilefrine in human leg veins in vitro and in situ." Int J Clin Pharmacol Ther Toxicol 25 (1987): 63-9. [PMID: 2881898]
• [15] Mendelson J, Jones RT, Upton R, Jacob P 3rd "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther 57 (1995): 559-68. [PMID: 7768079]