p-Hydroxynorephedrine

p-Hydroxynorephedrine
Identifiers
Synonyms 4-Hydroxynorephedrine
para-Hydroxynorephedrine
CAS Number 552-85-2 YesY
PubChem (CID) 11099
ChemSpider 10628 YesY
Chemical and physical data
Formula C9H13NO2
Molar mass 167.21 g/mol

p-Hydroxynorephedrine, or 4-hydroxynorephedrine, is the para-hydroxy analog of norephedrine and an active sympathomimetic metabolite of amphetamine in humans.[1][2] When it occurs as a metabolite of amphetamine, it is produced from both p-hydroxyamphetamine and norephedrine.[2][3][4]

Amphetamine metabolism

Metabolic pathways of amphetamine in humans[sources 1]
Graphic of several routes of amphetamine metabolism

Para-
Hydroxylation
Para-
Hydroxylation
Para-
Hydroxylation
unidentified
Beta-
Hydroxylation
Beta-
Hydroxylation
Oxidative
Deamination
Oxidation
unidentified
Glycine
Conjugation

The image above contains clickable links
In humans, para-hydroxynorephedrine is a metabolite of amphetamine. The hydroxylation of the substituted amphetamines in this image is mediated by CYP2D6 and dopamine β-hydroxylase.

See also

Reference notes

  1. ↑ [5][6][7][8][9][10][11][12][13]

References

  1. ↑ "p-Hydroxynorephedrine". NCBI. PubChem Compound. Retrieved 25 October 2013.
  2. 1 2 "Adderall XR Prescribing Information" (PDF). Medication Guide. United States Food and Drug Administration. Retrieved 7 October 2013.
  3. ↑ "Amphetamine: Biomedical Effects and Toxicity". NCBI. Pubchem Compound. Retrieved 12 October 2013.
  4. ↑ Santagati NA, Ferrara G, Marrazzo A, Ronsisvalle G (September 2002). "Simultaneous determination of amphetamine and one of its metabolites by HPLC with electrochemical detection". J. Pharm. Biomed. Anal. 30 (2): 247–55. doi:10.1016/S0731-7085(02)00330-8. PMID 12191709.
  5. ↑ "Adderall XR Prescribing Information" (PDF). United States Food and Drug Administration. Shire US Inc. December 2013. pp. 12–13. Retrieved 30 December 2013.
  6. ↑ Glennon RA (2013). "Phenylisopropylamine stimulants: amphetamine-related agents". In Lemke TL, Williams DA, Roche VF, Zito W. Foye's principles of medicinal chemistry (7th ed.). Philadelphia, USA: Wolters Kluwer Health/Lippincott Williams & Wilkins. pp. 646–648. ISBN 9781609133450. Retrieved 11 September 2015. The simplest unsubstituted phenylisopropylamine, 1-phenyl-2-aminopropane, or amphetamine, serves as a common structural template for hallucinogens and psychostimulants. Amphetamine produces central stimulant, anorectic, and sympathomimetic actions, and it is the prototype member of this class (39). ... The phase 1 metabolism of amphetamine analogs is catalyzed by two systems: cytochrome P450 and flavin monooxygenase. ... Amphetamine can also undergo aromatic hydroxylation to p-hydroxyamphetamine. ... Subsequent oxidation at the benzylic position by DA β-hydroxylase affords p-hydroxynorephedrine. Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine.
  7. ↑ Taylor KB (January 1974). "Dopamine-beta-hydroxylase. Stereochemical course of the reaction" (PDF). J. Biol. Chem. 249 (2): 454–458. PMID 4809526. Retrieved 6 November 2014. Dopamine-β-hydroxylase catalyzed the removal of the pro-R hydrogen atom and the production of 1-norephedrine, (2S,1R)-2-amino-1-hydroxyl-1-phenylpropane, from d-amphetamine.
  8. ↑ Horwitz D, Alexander RW, Lovenberg W, Keiser HR (May 1973). "Human serum dopamine-β-hydroxylase. Relationship to hypertension and sympathetic activity". Circ. Res. 32 (5): 594–599. doi:10.1161/01.RES.32.5.594. PMID 4713201. Subjects with exceptionally low levels of serum dopamine-β-hydroxylase activity showed normal cardiovascular function and normal β-hydroxylation of an administered synthetic substrate, hydroxyamphetamine.
  9. ↑ Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602Freely accessible. PMID 15922018.
    "Table 5: N-containing drugs and xenobiotics oxygenated by FMO"
  10. ↑ Cashman JR, Xiong YN, Xu L, Janowsky A (March 1999). "N-oxygenation of amphetamine and methamphetamine by the human flavin-containing monooxygenase (form 3): role in bioactivation and detoxication". J. Pharmacol. Exp. Ther. 288 (3): 1251–1260. PMID 10027866.
  11. ↑ Santagati NA, Ferrara G, Marrazzo A, Ronsisvalle G (September 2002). "Simultaneous determination of amphetamine and one of its metabolites by HPLC with electrochemical detection". J. Pharm. Biomed. Anal. 30 (2): 247–255. doi:10.1016/S0731-7085(02)00330-8. PMID 12191709.
  12. ↑ "Substrate/Product". butyrate-CoA ligase. BRENDA. Technische Universität Braunschweig. Retrieved 7 May 2014.
  13. ↑ "Substrate/Product". glycine N-acyltransferase. BRENDA. Technische Universität Braunschweig. Retrieved 7 May 2014.


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