Oxyfedrine

Oxyfedrine
Clinical data
Trade names	Ildamen, Modacor, Myofedrin
Other names	Oxyfedrin; Oxyphedrine; Oxyphedrin; Oxifedrine; Oxifedrin; Oxiphedrine; Oxiphedrin
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral, intravenous
Drug class	Sympathomimetic; Coronary vasodilator; β-Adrenergic receptor partial agonist; Norepinephrine releasing agent
ATC code	C01DX03 (WHO) ;
Pharmacokinetic data
Bioavailability	Oral: 85%
Protein binding	Almost 100%
Metabolites	• Norephedrine
Elimination half-life	4.2 hours
Excretion	Urine (active metabolites 90%)
Identifiers
	IUPAC name (RS)-3-[(2-Hydroxy-1-methyl-2-phenylethyl)amino]-1-(3-methoxyphenyl)propan-1-one;
CAS Number	15687-41-9 ;
PubChem CID	5489013;
ChemSpider	4590049;
UNII	DWL616XF1K;
KEGG	D08321 ;
ChEMBL	ChEMBL1651913;
CompTox Dashboard (EPA)	DTXSID0023408 ;
Chemical and physical data
Formula	C19H23NO3
Molar mass	313.397 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@@H]([C@@H](c1ccccc1)O)NCCC(=O)c2cccc(c2)OC;
	InChI 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]

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]

Research

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

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o 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.
^ ^a ^b ^c ^d ^e 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.
^ 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.
^ ^a ^b Schweizerischer Apotheker-Verein (2000). Index Nominum 2000: International Drug Directory. Medpharm Scientific Publishers. p. 777. ISBN 978-3-88763-075-1. Retrieved 29 August 2024.
^ 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.
^ ^a ^b "Oxyfedrine: Uses, Interactions, Mechanism of Action". DrugBank Online. 23 June 2017. Retrieved 29 August 2024.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ 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.
^ "List of Vasodilators". Archived from the original on 20 October 2012.
^ ^a ^b "List of Vasodilators". Archived from the original on 6 January 2021.
^ Thiele Kurt, U.S. patent 3,225,095 (1965 to Degussa)
^ 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.

[KirstenNelsonKirsten1998-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o 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.

[AppelPlanzPalm1975-2] 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.

[Elks2014-3] 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.

[IndexNominum2000-4] Schweizerischer Apotheker-Verein (2000). Index Nominum 2000: International Drug Directory. Medpharm Scientific Publishers. p. 777. ISBN 978-3-88763-075-1. Retrieved 29 August 2024.

[MortonHall2012-5] 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.

[DrugBank-6] "Oxyfedrine: Uses, Interactions, Mechanism of Action". DrugBank Online. 23 June 2017. Retrieved 29 August 2024.

[BeckettFoster1972-7] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ 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.

[Drugs.com-International-2012-8] "List of Vasodilators". Archived from the original on 20 October 2012.

[Drugs.com-International-2021-9] "List of Vasodilators". Archived from the original on 6 January 2021.

[10] Thiele Kurt, U.S. patent 3,225,095 (1965 to Degussa)

[pmid15802815-11] 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.

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