Dipivefrine, or dipivefrin, also known as epinephrine pivalate and sold under the brand name Propine among others, is a sympathomimetic

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

which is used in the treatment of open-angle glaucoma.Dipivefrin . It is available as a 0.1% ophthalmic

solution Solution may refer to: * Solution (chemistry), a mixture where one substance is dissolved in another * Solution (equation), in mathematics ** Numerical solution, in numerical analysis, approximate solutions within specified error bounds * Solu ...

(

eye drop Eye drops or eyedrops are liquid drops applied directly to the surface of the eye usually in small amounts such as a single drop or a few drops. Eye drops usually contain saline to match the salinity of the eye. Drops containing only saline ...

Side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of dipivefrine include local eye reactions among others. Dipivefrine is a

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

(adrenaline) and hence acts as a non-selective

adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like b ...

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

. It is a

substituted phenethylamine Substituted phenethylamines (or simply phenethylamines) are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative (chemistry), derivative compounds of phenethylamine ...

and

catecholamine A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. Cate ...

and is an

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

of epinephrine with much greater

fat solubility Lipophilicity (from Greek λίπος "fat" and φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are called lipophilic (translated as ...

. Dipivefrine was first described by 1975. It is widely marketed throughout the world. However, it is no longer available in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

Medical uses

Dipivefrine is used in the treatment of open-angle glaucoma.

Contraindications

Use in narrow-angle glaucoma may be dangerous because it could make the eye susceptible to an attack of angle closure, causing an increase in pressure and pain and possibly loss of vision.

Side effects

The most common

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of dipivefrine are burning, stinging, and other irritations of the eye. Possible but uncommon side effects are the same as those of epinephrine and include

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

(fast heartbeat),

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

(high blood pressure) and

arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...

s (irregular heartbeat).

Pharmacology

Dipivefrine penetrates the

cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...

and is then

hydrolysed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

to epinephrine by

esterase In biochemistry, an esterase is a class of enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis (and as such, it is a type of hydrolase). A wide range of different esterases exist that differ ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s. It increases outflow of the

aqueous humour The aqueous humour is a transparent water-like fluid similar to blood plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the po ...

and also reduces its formation (mediated by its action on α₁- and α₂-adrenergic receptors), thus reducing pressure inside the eye. It also increases the conductivity of

trabecular A trabecula (: trabeculae, from Latin for 'small beam') is a small, often microscopic, tissue element in the form of a small beam, strut or rod that supports or anchors a framework of parts within a body or organ. A trabecula generally has a ...

filtering cells (a β₂-adrenergic-receptor-mediated action). It is preferred to epinephrine because it is longer-acting, more consistent in its action, and better-tolerated.

Chemistry

Dipivefrine, also known as epinephrine dipivalate or as 3,4-dipivalyloxy-β-hydroxy-''N''-methylphenethylamine, is a

and

. It is the 3,4- dipivalate

(adrenaline). The experimental log P of dipivefrine is 1.7 and its predicted log P ranges from 1.49 to 3.71. It is dramatically more

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

(600-fold) than epinephrine, which is highly

hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...

and has a log P of -1.37. The lipophilicity of dipivefrine allows it to penetrate the

much more readily (17-fold) than epinephrine. Eye drops containing 0.1% dipivefrine have similar effectiveness to conventional eye drops containing 2% epinephrine in lowering

intraocular pressure Intraocular pressure (IOP) is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk of glaucoma. Most tonometers are calibrated t ...

. Dipivefrine is used pharmaceutically mainly as the

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternati ...

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

. A similar compound that was never marketed is pivenfrine, which is the 3-pivalate ester of

phenylephrine Phenylephrine, sold under the brand names Neosynephrine and Sudafed PE among others, is a medication used as a decongestant for uncomplicated nasal congestion in the form of a nasal spray or oral tablet, to dilate the pupil, to increase bloo ...

History

Dipivefrine was first described in the

scientific literature Scientific literature encompasses a vast body of academic papers that spans various disciplines within the natural and social sciences. It primarily consists of academic papers that present original empirical research and theoretical ...

by 1975.

Society and culture

Names

''Dipivefrine'' is the generic name of the drug and its , , and , while ''dipivefrin'' is its and ''dipivefrina'' is its . In the case of the

, ''dipivefrine hydrochloride'' is its while ''dipivefrin hydrochloride'' is its and . Synonyms of dipivefrine include ''epinephrine pivalate'', ''adrenaline pivalate'', and ''dipivalyl epinephrine'', among others. Dipivefrine has been sold under brand names including ''Diopine'', ''Glaucothil'', ''Pro-Epinephrine'', ''Propine'', ''Thilodrin'', and ''Vistapine'', among many others.

References

{{Adrenergic receptor modulators Alpha-1 adrenergic receptor agonists Alpha-2 adrenergic receptor agonists Beta-adrenergic agonists Catechol ethers Catecholamines Monoamine precursors Ophthalmology drugs Phenylethanolamines Pivalate esters Prodrugs