Methylephedrine

Last updated

Methylephedrine
N-Methylephedrin.svg
Clinical data
Trade names Metheph, Methy-F, Tybraine
Other namesN-Methylephedrine; N-Methyl-(–)-ephedrine; L-Methylephedrine; N-Methyl-L-ephedrine; (−)-N-Methylephedrine; N,N-Dimethylnorephedrine
Drug class Sympathomimetic; Norepinephrine releasing agent; Bronchodilator; Nasal decongestant; Antitussive
Pharmacokinetic data
Metabolites • Methylephedrine N-oxide [1] [2]
• Ephedrine [1] [2]
• Norephedrine [1] [2]
Excretion Urine [1]
Identifiers
  • (1R,2S)-2-(dimethylamino)-1-phenylpropan-1-ol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.008.203 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C11H17NO
Molar mass 179.263 g·mol−1
3D model (JSmol)
  • C[C@@H]([C@@H](C1=CC=CC=C1)O)N(C)C
  • InChI=1S/C11H17NO/c1-9(12(2)3)11(13)10-7-5-4-6-8-10/h4-9,11,13H,1-3H3/t9-,11-/m0/s1
  • Key:FMCGSUUBYTWNDP-ONGXEEELSA-N

Methylephedrine, sold under the brand name Metheph among others, is a sympathomimetic medication described as an antiasthmatic agent and used to treat coughing and nasal congestion. [3] [4] [1] It is reported to be used in various over-the-counter cough and cold preparations throughout the world, including Japan. [1]

Contents

The drug is an ephedrine-like sympathomimetic and activates α- and β-adrenergic receptors. [5] Chemically, it is a substituted amphetamine and is closely related to ephedrine. [3] [4]

Methylephedrine was discovered by 1927. [6] It is mostly no longer marketed as a prescription drug. [4] The drug is also found naturally as an alkaloid in Ephedra species including Ephedra sinica , Ephedra vulgaris , and Ephedra distachya . [3] [6]

Side effects

Rarely, heart failure and stroke in association with use of methylephedrine have been reported. [7] [8] [9]

Methylephedrine shows reinforcing effects, a measure of addiction and misuse potential, in monkeys. [10]

Pharmacology

Pharmacodynamics

Methylephedrine is a sympathomimetic and ephedrine-like agent. [5] [1] Ephedrine and related agents act as norepinephrine releasing agents and hence as indirectly acting sympathomimetics. [1] In relation to this, methylephedrine stimulates α- and β-adrenergic receptors. [5] [1] The drug has bronchodilator and nasal decongestant effects. [5]

The occupancy of the dopamine transporter (DAT) by racemic methylephedrine has been studied. [11]

Pharmacokinetics

Methylephedrine is metabolized into ephedrine and norephedrine. [1] [2] It is excreted in urine 33 to 40% unchanged, 15% as methylephedrine N-oxide, and 8% as ephedrine after 24 hours. [1] [2]

Chemistry

Methylephedrine, also known as (1R,2S)-β-hydroxy-N,N-dimethyl-α-methyl-β-phenethylamine and as (1R,2S)-β-hydroxy-N,N-dimethylamphetamine, is a substituted phenethylamine and amphetamine derivative. [3] [4] It is the N-methylated derivative of ephedrine ((1R,2S)-β-hydroxy-N-methylamphetamine). [3] [4]

A closely related compound and stereoisomer of methylephedrine is N-methylpseudoephedrine. [3] Another related analogue is dimethylamphetamine (N,N-dimethylamphetamine), which is said to be a prodrug of methamphetamine and/or amphetamine. [12] Other analogues include etafedrine (N-ethylephedrine) and cinnamedrine (N-cinnamylephedrine). [3]

The experimental log P of methylephedrine is 2.47 and its predicted log P ranges from 1.7 to 1.74. [13] [1] [14]

In organic chemistry, N-methylephedrine is used as a resolving agent and as a precursor to chiral supporting electrolytes, phase-transfer catalysts, and reducing agents. [15]

History

Methylephedrine was discovered via isolation from Ephedra by 1927. [6]

Society and culture

Names

Methylephedrine is the generic name of the drug and its BAN Tooltip British Approved Name. [3] [4] [16] In the case of the hydrochloride salt, its generic name is methylephedrine hydrochloride and this is its BANM Tooltip British Approved Name. [3] [4] [16] Brand names of methylephedrine include Metheph, Methy-F, and Tybraine, among others. [3] [4] [16]

Recreational use

Similarly to ephedrine, methylephedrine may have misuse potential. [1] [17] The drug shows reinforcing effects in monkeys. [10] It is one of the four constituents of BRON, a Japanese over-the-counter cough medicine with reports of misuse. [1] [17] However, addiction liability of BRON was attributed primarily to the codeine component. [17] A case report of addiction to methylephedrine exists. [9]

Use in sports and exercise

Methylephedrine is on the World Anti-Doping Agency's prohibited list. [5]

Related Research Articles

<span class="mw-page-title-main">Pseudoephedrine</span> Pharmaceutical drug

Pseudoephedrine, sold under the brand name Sudafed among others, is a sympathomimetic medication which is used as a decongestant to treat nasal congestion. It has also been used off-label for certain other indications, like treatment of low blood pressure. At higher doses, it may produce various additional effects, including psychostimulant, appetite suppressant, and performance-enhancing effects. In relation to this, non-medical use of pseudoephedrine has been encountered. The medication is taken by mouth.

<span class="mw-page-title-main">Ephedrine</span> Medication and stimulant

Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in nasal congestion. It can be taken by mouth or by injection into a muscle, vein, or just under the skin. Onset with intravenous use is fast, while injection into a muscle can take 20 minutes, and by mouth can take an hour for effect. When given by injection, it lasts about an hour, and when taken by mouth, it can last up to four hours.

<span class="mw-page-title-main">Phenylpropanolamine</span> Sympathomimetic agent

Phenylpropanolamine (PPA), sold under many brand names, is a sympathomimetic agent which is used as a decongestant and appetite suppressant. It was previously commonly used in prescription and over-the-counter cough and cold preparations. The medication is taken by mouth.

<span class="mw-page-title-main">Sympathomimetic drug</span> Substance that mimics effects of catecholamines

Sympathomimetic drugs are stimulant compounds which mimic the effects of endogenous agonists of the sympathetic nervous system. Examples of sympathomimetic effects include increases in heart rate, force of cardiac contraction, and blood pressure. The primary endogenous agonists of the sympathetic nervous system are the catecholamines, which function as both neurotransmitters and hormones. Sympathomimetic drugs are used to treat cardiac arrest and low blood pressure, or even delay premature labor, among other things.

<span class="mw-page-title-main">4-Hydroxyamphetamine</span> Group of stereoisomers

Hydroxyamphetamine, also known as 4-hydroxyamphetamine or norpholedrine and sold under the brand names Paredrine and Paremyd among others, is a sympathomimetic medication used in eye drops to dilate the pupil for eye examinations.

<span class="mw-page-title-main">Metaraminol</span> Antihypotensive medication

Metaraminol, also known as metaradrine and sold under the brand names Aramine and Pressonex among others, is a sympathomimetic medication which is used in the prevention and treatment of hypotension, particularly as a complication of anesthesia. It is given by intramuscular or intravenous administration.

<span class="mw-page-title-main">Methoxamine</span> Chemical compound

Methoxamine, sold under the brand names Vasoxine, Vasoxyl, and Vasylox among others, is a sympathomimetic medication used as an antihypotensive agent. It has mostly or entirely been discontinued.

<span class="mw-page-title-main">Gepefrine</span> Sympathomimetic drug in the amphetamine family

Gepefrine, also known as 3-hydroxyamphetamine or α-methyl-meta-tyramine and sold under the brand names Pressionorm and Wintonin, is a sympathomimetic medication used as an antihypotensive agent which has been marketed in Germany.

<span class="mw-page-title-main">Prenalterol</span> Chemical compound

Prenalterol, sold under the brand name Hyprenan, is a sympathomimetic agent and cardiac stimulant which acts as a β1-adrenergic receptor partial agonist and is used in the treatment of heart failure. It has selectivity for the β1-adrenergic receptor. Its partial agonist activity or intrinsic sympathomimetic activity is about 60%. It is said to have much greater impact on myocardial contractility than on heart rate. The drug has been marketed in Denmark, Norway, and Sweden.

<span class="mw-page-title-main">Mephentermine</span> Adrenergic and dopaminergic cardiac stimulant

Mephentermine, sold under the brand name Wyamine among others, is a sympathomimetic medication which was previously used in the treatment of low blood pressure but is mostly no longer marketed. It is used by injection into a vein or muscle, by inhalation, and by mouth.

<span class="mw-page-title-main">Norfenefrine</span> Sympathomimetic drug

Norfenefrine, also known as meta-octopamine or norphenylephrine and sold under the brand name Novadral among others, is a sympathomimetic medication which is used in the treatment of hypotension. Along with its structural isomer p-octopamine and the tyramines, norfenefrine is a naturally occurring endogenous trace amine and plays a role as a minor neurotransmitter in the brain.

<span class="mw-page-title-main">Etilefrine</span> Chemical compound

Etilefrine, sold under the brand name Effortil among others, is a sympathomimetic medication used as an antihypotensive agent to treat orthostatic hypotension. It is usually used by mouth, but is also available as an injectable.

<span class="mw-page-title-main">Oxyfedrine</span> Chemical compound

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. It is taken by mouth or intravenously.

<span class="mw-page-title-main">Amidephrine</span> Chemical compound

Amidephrine, or amidefrine, sold under the brand name Fentrinol among others, is a selective α1-adrenergic receptor agonist which is described as an adrenergic or sympathomimetic, vasoconstrictor, and topical nasal decongestant used to treat allergic rhinitis. It is used as the mesylate salt, which has the generic names amidefrine mesilate and amidephrine mesylate. The drug is a substituted phenethylamine derivative and is also known as 3-methylsulfonamidyl-β-hydroxy-N-methylphenethylamine. As of 2000, it remained marketed only in Austria.

<span class="mw-page-title-main">Pholedrine</span> Chemical compound

Pholedrine, also known as 4-hydroxy-N-methylamphetamine and sold under the brand names Paredrinol, Pulsotyl, and Veritol among others, is a sympathomimetic drug used in topical eye drops to dilate the pupil. It can be used to diagnose Horner's syndrome.

Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with substituents. The compounds in this class span a variety of pharmacological subclasses, including stimulants, empathogens, and hallucinogens, among others. Examples of substituted amphetamines are amphetamine (itself), methamphetamine, ephedrine, cathinone, phentermine, mephentermine, tranylcypromine, bupropion, methoxyphenamine, selegiline, amfepramone (diethylpropion), pyrovalerone, MDMA (ecstasy), and DOM (STP).

Oxilofrine, sold under the brand names Carnigen and Suprifen among others, is a sympathomimetic medication which has been used as an antihypotensive agent and cough suppressant. It is taken by mouth.

<span class="mw-page-title-main">Racephedrine</span> Pharmaceutical drug

Racephedrine, also known as racemic ephedrine and sold under the brand names Efetonina and Ephoxamine among others, is the racemic form of ephedrine which has been used as a bronchodilator to treat asthma. More specifically, it is a racemic mixture of (1R,2S)- and (1S,2R)-enantiomers. Conversely, ephedrine is the enantiopure (1R,2S)-enantiomer. Racephedrine has been marketed for medical use in Italy. Like ephedrine, racephedrine is a releasing agent of norepinephrine and to a much lesser extent of dopamine. Both ephedrine enantiomers are active in this regard, but ephedrine ( -ephedrine) has greater potency than (1S,2R)-ephedrine.

<span class="mw-page-title-main">Substituted β-hydroxyamphetamine</span> Class of compounds based upon the β-hydroxyamphetamine structure

Substituted β-hydroxyamphetamines, also known as substituted phenylisopropanolamines, substituted phenylpropanolamines, substituted norephedrines, or substituted cathinols, are derivatives of β-hydroxyamphetamine with one or more chemical substituents. They are substituted phenethylamines, phenylethanolamines (β-hydroxyphenethylamines), and amphetamines (α-methylphenethylamines), and are closely related to but distinct from the substituted cathinones (β-ketoamphetamines). Examples of β-hydroxyamphetamines include the β-hydroxyamphetamine stereoisomers phenylpropanolamine and cathine and the stereospecific N-methylated β-hydroxyamphetamine derivatives ephedrine and pseudoephedrine, among many others.

<span class="mw-page-title-main">Racefemine</span> Tocolytic

Racefemine, sold under the brand names Dysmalgine and Evalgin, is a uterine spasmolytic and muscle relaxant of the amphetamine family. It is the racemic threo form of dextrofemine. The drug acts as a β-adrenergic receptor agonist and sympathomimetic. It appears to no longer be marketed. Other tocolytics with similar chemical structures as phenethylamines or amphetamines include bedoradrine, buphenine, fenoterol, hexoprenaline, isoxsuprine, ritodrine, and terbutaline.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "DL-Methylephedrine: Uses, Interactions, Mechanism of Action". DrugBank Online. 22 November 2018. Retrieved 1 September 2024.
  2. 1 2 3 4 5 Inoue T, Suzuki S (January 1990). "The metabolism of (+-)-methylephedrine in rat and man". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 20 (1): 99–106. doi:10.3109/00498259009046816. PMID   2327112.
  3. 1 2 3 4 5 6 7 8 9 10 Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 435. ISBN   978-1-4757-2085-3 . Retrieved 2024-09-01.
  4. 1 2 3 4 5 6 7 8 Schweizerischer Apotheker-Verein (2004). Index Nominum: International Drug Directory. Medpharm Scientific Publishers. p. 783. ISBN   978-3-88763-101-7 . Retrieved 1 September 2024.
  5. 1 2 3 4 5 Docherty JR (June 2008). "Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)". British Journal of Pharmacology. 154 (3): 606–622. doi:10.1038/bjp.2008.124. PMC   2439527 . PMID   18500382.
  6. 1 2 3 Smith (1927). "CCLXX. l-Methylephedrine, an alkaloid from Ephedra species". J. Chem. Soc.: 2056–2059. doi:10.1039/jr9270002056.
  7. ↑ Suzuki M, Higashi H, Ikeda S, Yamaguchi O (June 2020). "Methylephedrine-induced heart failure in a habitual user of paediatric cough syrup: a case report". European Heart Journal: Case Reports. 4 (3): 1–4. doi:10.1093/ehjcr/ytaa095. PMC   7319816 . PMID   32617471.
  8. ↑ Imai N, Yagi N, Konishi T, Serizawa M, Kobari M (2010). "Ischemic stroke associated with cough and cold preparation containing methylephedrine and supplement containing Chinese herbal drugs". Internal Medicine. 49 (4): 335–338. doi:10.2169/internalmedicine.49.2704. PMID   20154441.
  9. 1 2 Kunieda T, Imai K, Mori T, Izumoto H, Takabatake N, Yamamoto S (April 2006). "[Ischemic stroke in a young patient with methylephedrine addiction: a case report]". Rinsho Shinkeigaku = Clinical Neurology (in Japanese). 46 (4): 274–277. PMID   16768095.
  10. 1 2 Sekita K, Ochiai T, Ohno K, Murakami O, Wakasa Y, Uzawa K, et al. (1992). "[Studies on reinforcing effects of methylephedrine, caffeine and their mixture with intravenous-self administration in rhesus monkeys]". Eisei Shikenjo Hokoku. Bulletin of National Institute of Hygienic Sciences (in Japanese) (110): 15–22. PMID   1364430.
  11. ↑ Nogami T, Arakawa R, Sakayori T, Ikeda Y, Okubo Y, Tateno A (2022). "Effect of DL-Methylephedrine on Dopamine Transporter Using Positron Emission Tomography With [18F]FE-PE2I". Frontiers in Psychiatry. 13: 799319. doi: 10.3389/fpsyt.2022.799319 . PMC   9193582 . PMID   35711596.
  12. ↑ Dettmeyer R, Verhoff MA, Schütz HF (9 October 2013). Forensic Medicine: Fundamentals and Perspectives. Springer Science & Business Media. pp. 519–. ISBN   978-3-642-38818-7.
  13. ↑ "(1R,2S)-2-(dimethylamino)-1-phenylpropan-1-ol". PubChem. Retrieved 1 September 2024.
  14. ↑ "(−)-N-Methylephedrine". ChemSpider. 2024-09-01. Retrieved 2024-09-01.
  15. ↑ (1R,2S)-(−)-N-Methylephedrine at Sigma-Aldrich
  16. 1 2 3 Schweizerischer Apotheker-Verein (2000). Index Nominum 2000: International Drug Directory. Medpharm Scientific Publishers. p. 672. ISBN   978-3-88763-075-1 . Retrieved 1 September 2024.
  17. 1 2 3 Ishigooka J, Yoshida Y, Murasaki M (1991-01-01). "Abuse of "BRON": a Japanese OTC cough suppressant solution containing methylephedrine, codeine, caffeine and chlorpheniramine". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 15 (4): 513–521. doi:10.1016/0278-5846(91)90026-W. PMID   1749828. S2CID   53187238.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.