Dipivefrine

"Propine" redirects here. For the hydrocarbon compound, see propyne.
Dipivefrine
Clinical data
Trade namesAKPro, D Epifrin, Diopine, Glaucothil, Pro-Epinephrine, Propine, Pivalephrine, Thilodrin, Vistapine, others
Other namesDipivefrin; Dipivephrine; Dipivephrin; Dipivalyl epinephrine; Dipivalylepinephrine; DPE; Epinephrine dipivalate; Epinephrine dipivalate ester; Adrenaline dipivalate; K-30081; 3,4-Dipivalyloxy-β-hydroxy-N-methylphenethylamine; 3,4-Dipivalyloxy-β-hydroxy-N-methyl-β-phenylethylamine
AHFS/Drugs.comInternational Drug Names
MedlinePlusa686005
Routes of
administration		Eye drops[1]
Drug classAdrenergic receptor agonist; Sympathomimetic
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
  • [2-(2,2-Dimethylpropanoyloxy)-4-(1-hydroxy-2-methylamino-ethyl)-phenyl] 2,2-dimethylpropanoate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC19H29NO5
Molar mass351.443 g·mol−1
3D model (JSmol)
  • O=C(Oc1cc(ccc1OC(=O)C(C)(C)C)C(O)CNC)C(C)(C)C
  • 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 checkY
  • Key:OCUJLLGVOUDECM-UHFFFAOYSA-N checkY
  (verify)

Dipivefrine, or dipivefrin, also known as epinephrine pivalate and sold under the brand name Propine among others, is a sympathomimetic medication which is used in the treatment of open-angle glaucoma.[2][3] It is available as a 0.1% ophthalmic solution (eye drop).[1][4]

Side effects of dipivefrine include local eye reactions among others. Dipivefrine is a prodrug of epinephrine (adrenaline) and hence acts as a non-selective adrenergic receptor agonist.[5] It is a substituted phenethylamine and catecholamine and is an ester of epinephrine with much greater fat solubility.[6][7][8]

Dipivefrine was first described by 1975.[9] It is widely marketed throughout the world.[10] However, it is no longer available in the United States.[11]

Medical uses

Dipivefrine is used in the treatment of open-angle glaucoma.[2]

Contraindications

Use in narrow-angle glaucoma may be dangerous because it could make the eye susceptible to an attack of angle closure,[3] causing an increase in pressure and pain and possibly loss of vision.

Side effects

The most common side effects 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 (fast heartbeat), hypertension (high blood pressure) and arrhythmias (irregular heartbeat).[3]

Pharmacology

Dipivefrine penetrates the cornea and is then hydrolysed to epinephrine by esterase enzymes.[8] It increases outflow of the aqueous humour 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 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.[2]

Chemistry

Dipivefrine, also known as epinephrine dipivalate or as 3,4-dipivalyloxy-β-hydroxy-N-methylphenethylamine, is a substituted phenethylamine and catecholamine.[6] It is the 3,4-dipivalate ester of epinephrine (adrenaline).[6]

The experimental log P of dipivefrine is 1.7 and its predicted log P ranges from 1.49 to 3.71.[6][1][12] It is dramatically more lipophilic (600-fold) than epinephrine,[7][8][4] which is highly hydrophilic and has a log P of -1.37.[13] The lipophilicity of dipivefrine allows it to penetrate the cornea much more readily (17-fold) than epinephrine.[7][8][4] Eye drops containing 0.1% dipivefrine have similar effectiveness to conventional eye drops containing 2% epinephrine in lowering intraocular pressure.[4]

Dipivefrine is used pharmaceutically mainly as the hydrochloride salt.[14][10]

A similar compound that was never marketed is pivenfrine, which is the 3-pivalate ester of phenylephrine.[14]

History

Dipivefrine was first described in the scientific literature by 1975.[9]

Society and culture

Names

Dipivefrine is the generic name of the drug and its INNTooltip International Nonproprietary Name, BANTooltip British Approved Name, and DCFTooltip Dénomination Commune Française, while dipivefrin is its USANTooltip United States Adopted Name and dipivefrina is its DCITTooltip Denominazione Comune Italiana.[14][10][15] In the case of the hydrochloride salt, dipivefrine hydrochloride is its BANMTooltip British Approved Name while dipivefrin hydrochloride is its USANTooltip United States Adopted Name and JANTooltip Japanese Accepted Name.[14][10][15]

Synonyms of dipivefrine include epinephrine pivalate, adrenaline pivalate, and dipivalyl epinephrine, among others.[14][10]

Dipivefrine has been sold under brand names including Diopine, Glaucothil, Pro-Epinephrine, Propine, Thilodrin, and Vistapine, among many others.[14][10]

See also

References

  1. ^ a b c "Dipivefrin: Uses, Interactions, Mechanism of Action". DrugBank Online. 31 December 1995. Retrieved 31 August 2024.
  2. ^ a b c KD Tripari (2004). Essentials of Medical Pharmacology (5 ed.). Jaypee Brothers Medical Publishers(P) Ltd. p. 88. ISBN 81-8061-187-6.
  3. ^ a b c Dipivefrin FDA Professional Drug Information.
  4. ^ a b c d Baranowski P, Karolewicz B, Gajda M, Pluta J (2014). "Ophthalmic drug dosage forms: characterisation and research methods". ScientificWorldJournal. 2014: 861904. doi:10.1155/2014/861904. PMC 3977496. PMID 24772038.
  5. ^ Arthur S, Cantor LB (September 2011). "Update on the role of alpha-agonists in glaucoma management". Exp Eye Res. 93 (3): 271–283. doi:10.1016/j.exer.2011.04.002. PMID 21524649.
  6. ^ a b c d "Dipivefrin". PubChem. Retrieved 31 August 2024.
  7. ^ a b c Goldberg I, Kolker AE, Kass MA, Becker B (May 1980). "Dipivefrin: current concepts". Aust J Ophthalmol. 8 (2): 147–150. doi:10.1111/j.1442-9071.1980.tb01673.x. PMID 7004425.
  8. ^ a b c d Stella V, Borchardt R, Hageman M, Oliyai R, Maag H, Tilley J (2007). Prodrugs: Challenges and Rewards. Biotechnology: Pharmaceutical Aspects. Springer New York. p. 130. ISBN 978-0-387-49782-2. Retrieved 2024-08-31.
  9. ^ a b McClure DA (1 June 1975). "The Effect of a Pro-drug of Epinephrine (Dipivalyl Epinephrine) in Glaucoma—General Pharmacology, Toxicology, and Clinical Experience". Pro-drugs as Novel Drug Delivery Systems. Vol. 14. Washington, D. C.: American Chemical Society. pp. 225–235. doi:10.1021/bk-1975-0014.ch006. ISBN 978-0-8412-0291-7.
  10. ^ a b c d e f Schweizerischer Apotheker-Verein (2004). Index Nominum: International Drug Directory. Medpharm Scientific Publishers. p. 411. ISBN 978-3-88763-101-7. Retrieved 2024-08-31.
  11. ^ Zhang L, Weizer JS, Musch DC (2017). "Perioperative medications for preventing temporarily increased intraocular pressure after laser trabeculoplasty". Cochrane Database Syst Rev. 2017 (2): CD010746. doi:10.1002/14651858.CD010746.pub2. PMC 5477062. PMID 28231380.
  12. ^ "C19H29NO5". Dipivefrin (in Latin). 31 August 2024. Retrieved 31 August 2024.
  13. ^ "Epinephrine". PubChem. Retrieved 31 August 2024.
  14. ^ a b c d e f Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. pp. 455, 1001. ISBN 978-1-4757-2085-3. Retrieved 2024-08-31.
  15. ^ a b Morton IK, Hall JM (2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Netherlands. p. 101. ISBN 978-94-011-4439-1. Retrieved 31 August 2024.