Oxyfedrine

Last updated

Oxyfedrine
Oxyfedrine.svg
Clinical data
Trade names Ildamen, Modacor, Myofedrin
Other namesOxyfedrin; Oxyphedrine; Oxyphedrin; Oxifedrine; Oxifedrin; Oxiphedrine; Oxiphedrin
AHFS/Drugs.com International Drug Names
Routes of
administration
Oral, intravenous [1]
Drug class Sympathomimetic; Coronary vasodilator; β-Adrenergic receptor partial agonist; Norepinephrine releasing agent
ATC code
Pharmacokinetic data
Bioavailability Oral: 85% [1]
Protein binding Almost 100% [1]
Metabolites Norephedrine [2]
Elimination half-life 4.2 hours [1]
Excretion Urine (active metabolites 90%) [1]
Identifiers
  • (RS)-3-[(2-Hydroxy-1-methyl-2-phenylethyl)amino]-1-(3-methoxyphenyl)propan-1-one
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C19H23NO3
Molar mass 313.397 g·mol−1
3D model (JSmol)
  • C[C@@H]([C@@H](c1ccccc1)O)NCCC(=O)c2cccc(c2)OC
  • InChI=1S/C19H23NO3/c1-14(19(22)15-7-4-3-5-8-15)20-12-11-18(21)16-9-6-10-17(13-16)23-2/h3-10,13-14,19-20,22H,11-12H2,1-2H3/t14-,19-/m0/s1
  • Key:GDYUVHBMFVMBAF-LIRRHRJNSA-N
   (verify)

Oxyfedrine, sold under the brand names Ildamen and Myofedrin among others, is a sympathomimetic agent and coronary vasodilator which is used in the treatment of coronary heart disease, angina pectoris, and acute myocardial infarction. [1] [3] [4] [5] [6] [7] It is taken by mouth or intravenously. [1]

Contents

The drug acts as a β-adrenergic receptor partial agonist. [1] [7] It may also act as a norepinephrine releasing agent via its major active metabolite norephedrine. [2] Oxyfedrine is a phenethylamine and amphetamine derivative. [6] [7]

Oxyfedrine has been marketed in Europe, Hong Kong, India, Central America, and elsewhere. [4] [8] [9] It appears to remain marketed only in India. [9]

Pharmacology

Pharmacodynamics

Oxyfedrine is a β-adrenergic receptor partial agonist. [1] [7] It appears to be non-selective for the β1- and β2-adrenergic receptors. [7] It is selective for the β-adrenergic receptors over the α-adrenergic receptors. [7] However, it has also been reported to interact with the α-adrenergic receptors at high concentrations, acting as a partial agonist or antagonist of these receptors. [7] Norephedrine, a norepinephrine releasing agent, is a major active metabolite of oxyfedrine, and hence oxyfedrine may additionally act as an indirectly acting sympathomimetic. [2]

It has been found to depress the tonicity of coronary vessels, improve myocardial metabolism (so that heart can sustain hypoxia better) and also exert a positive chronotropic and inotropic effects, [1] thereby not precipitating angina pectoris. The latter property (positive chronotropic and inotropic effects) is particularly important, because other vasodilators used in angina may be counter productive causing coronary steal phenomenon.[ additional citation(s) needed ]

The drug is chemically and pharmacologically unrelated to any other antianginal drugs. [1]

Pharmacokinetics

Oxyfedrine's oral bioavailability is 85%. [1] The plasma protein binding is almost 100%. [1] Its elimination half-life is 4.2 hours. [1] Norephedrine is a major active metabolite of oxyfedrine. [2] The excretion of the active metabolites of oxyfedrine is 90% in urine. [1] About 75 to 100% of oxyfedrine is excreted as norephedrine. [2]

Chemistry

Oxyfedrine is a substituted phenethylamine and amphetamine derivative. [7] It is l-norephedrine with a bulky and lipophilic 3-methoxypropiophenone substituent at the nitrogen atom. [7]

Synthesis

Mannich condensation of phenylpropanolamine (1) with formaldehyde and m-acetanisole (3-acetylanisole) (2) yields oxyfedrine (3). [10]

Oxyfedrine synthesis.svg

Research

Synergistic effects of oxyfedrine with antibiotics against bacteria have been suggested. [11]

Related Research Articles

An antianginal is a drug used in the treatment of angina pectoris, a symptom of ischaemic heart disease.

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References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Kirsten R, Nelson K, Kirsten D, Heintz B (July 1998). "Clinical pharmacokinetics of vasodilators. Part II". Clin Pharmacokinet. 35 (1): 9–36. doi:10.2165/00003088-199835010-00002. PMID   9673832.
  2. 1 2 3 4 5 Appel E, Planz G, Palm D, Grobecker H, Stratmann D, Donike M (April 1975). "Excretion of norephedrine by man after oral administration of oxyfedrine". Eur J Clin Pharmacol. 8 (3–4): 161–166. doi:10.1007/BF00567109. PMID   1233214.
  3. Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 923. ISBN   978-1-4757-2085-3 . Retrieved 29 August 2024.
  4. 1 2 Schweizerischer Apotheker-Verein (2000). Index Nominum 2000: International Drug Directory. Index nominum. Medpharm Scientific Publishers. p. 777. ISBN   978-3-88763-075-1 . Retrieved 29 August 2024.
  5. Morton IK, Hall JM (2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Netherlands. p. 212. ISBN   978-94-011-4439-1 . Retrieved 2024-08-29.
  6. 1 2 "Oxyfedrine: Uses, Interactions, Mechanism of Action". DrugBank Online. 23 June 2017. Retrieved 29 August 2024.
  7. 1 2 3 4 5 6 7 8 9 Beckett PR, Foster RW (November 1972). "Oxyfedrine--a partial agonist at -adrenoceptors". Eur J Pharmacol. 20 (2): 161–170. doi:10.1016/0014-2999(72)90145-8. PMID   4405576.
  8. https://web.archive.org/web/20121020185501/https://www.drugs.com/international/oxyfedrine.html
  9. 1 2 https://web.archive.org/web/20210106003945/https://www.drugs.com/international/oxyfedrine.html
  10. Thiele Kurt, U.S. patent 3,225,095 (1965 to Degussa)
  11. Mazumdar K, Dutta NK, Kumar KA, Dastidar SG (April 2005). "In vitro and in vivo synergism between tetracycline and the cardiovascular agent oxyfedrine HCl against common bacterial strains". Biological & Pharmaceutical Bulletin. 28 (4): 713–7. doi: 10.1248/bpb.28.713 . PMID   15802815.