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Norepinephrine releasing agent

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Ephedrine, one of the most well-known selective NRAs.

A norepinephrine releasing agent (NRA), also known as an adrenergic releasing agent, is a catecholaminergic type of drug that induces the release of norepinephrine (noradrenaline) and epinephrine (adrenaline) from the pre-synaptic neuron into the synapse.[1][2] This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine therefore an increase in adrenergic neurotransmission.[1][2][3][4]

A closely related type of drug is a norepinephrine reuptake inhibitor (NRI), for instance reboxetine.[5][6] Another class of drugs that stimulates adrenergic activity is the adrenergic receptor agonist class.[7]

Uses and examples

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NRAs, frequently as norepinephrine–dopamine releasing agents (NDRAs) rather than as selective NRAs, are used for a variety of clinical indications including the following:[1][2][8][9]

They are also used as recreational drugs, though this is typically reserved only for those that also induce the release of dopamine and/or serotonin, for instance amphetamine, methamphetamine, MDMA, mephedrone, 4-methylaminorex, and MDAI, among others.[17][18][19][20]

Cathine and cathinone are NRAs found naturally in Catha edulis.[21][22] Ephedrine and pseudoephedrine are also found naturally in Ephedra sinica.[21][22][23] Both of these plants are used medicinally (and recreationally as well regarding the former).[21][22][23] The endogenous trace amines phenethylamine and tyramine are NRAs found in many animals, including humans.[24][1][2]

Selective NRAs include ephedrine, pseudoephedrine, phenylpropanolamine, and levomethamphetamine.[1][2][23] These drugs also release dopamine to a much lesser extent however.[1][2][23] In contrast to levomethamphetamine, levoamphetamine is an NDRA.[19] NRAs play a significant role in treating ADHD, obesity, narcolepsy, and as sympathomimetics by enhancing adrenergic signaling.[1][2][8][25]

See also

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References

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  1. ^ a b c d e f g Rothman RB, Baumann MH (October 2003). "Monoamine transporters and psychostimulant drugs". European Journal of Pharmacology. 479 (1–3): 23–40. doi:10.1016/j.ejphar.2003.08.054. PMID 14612135.
  2. ^ a b c d e f g Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–1859. doi:10.2174/156802606778249766. PMID 17017961.
  3. ^ Parker K, Brunton L, Goodman LS, Lazo JS, Gilman A (2006). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11 ed.). New York: McGraw-Hill. ISBN 0-07-142280-3. Archived from the original on 2011-11-18. Retrieved 2011-06-26.
  4. ^ Foye W, Lemke T, Williams D (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. ISBN 978-0-7817-6879-5. Retrieved 7 December 2024.
  5. ^ N Maiti S, P Kamalesh Babu R (2006). "Norepinephrine Reuptake Inhibitors for Depression, ADHD and Other Neuropsychiatric Disorders". Heterocycles. 69 (1): 539. doi:10.3987/REV-06-SR(O)1. ISSN 0385-5414.
  6. ^ Liu S, Molino BF (2007). "Chapter 2 Recent Developments in Monoamine Reuptake Inhibitors". Annual Reports in Medicinal Chemistry. Vol. 42. Elsevier. pp. 13–26. doi:10.1016/s0065-7743(07)42002-4. ISBN 978-0-12-373912-4.
  7. ^ Stanford SC, Heal DJ (2019). "Catecholamines: Knowledge and understanding in the 1960s, now, and in the future". Brain Neurosci Adv. 3: 2398212818810682. doi:10.1177/2398212818810682. PMC 7058270. PMID 32166174.
  8. ^ a b c d Heal DJ, Smith SL, Gosden J, Nutt DJ (June 2013). "Amphetamine, past and present--a pharmacological and clinical perspective". Journal of Psychopharmacology. 27 (6): 479–496. doi:10.1177/0269881113482532. PMC 3666194. PMID 23539642.
  9. ^ a b c Rasmussen N (2015). "Amphetamine-Type Stimulants: The Early History of Their Medical and Non-Medical Uses". Int Rev Neurobiol. 120: 9–25. doi:10.1016/bs.irn.2015.02.001. PMID 26070751.
  10. ^ Heal DJ, Cheetham SC, Smith SL (December 2009). "The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety". Neuropharmacology. 57 (7–8): 608–618. doi:10.1016/j.neuropharm.2009.08.020. PMID 19761781.
  11. ^ Heal DJ, Smith SL (June 2022). "Prospects for new drugs to treat binge-eating disorder: Insights from psychopathology and neuropharmacology". J Psychopharmacol. 36 (6): 680–703. doi:10.1177/02698811211032475. PMC 9150143. PMID 34318734.
  12. ^ Nishino S, Kotorii N (2016). "Overview of Management of Narcolepsy". Narcolepsy. Cham: Springer International Publishing. pp. 285–305. doi:10.1007/978-3-319-23739-8_21. ISBN 978-3-319-23738-1.
  13. ^ Nishino S, Kotorii N (2016). "Modes of Action of Drugs Related to Narcolepsy: Pharmacology of Wake-Promoting Compounds and Anticataplectics". Narcolepsy. Cham: Springer International Publishing. pp. 307–329. doi:10.1007/978-3-319-23739-8_22. ISBN 978-3-319-23738-1.
  14. ^ Aaron CK (August 1990). "Sympathomimetics". Emerg Med Clin North Am. 8 (3): 513–526. doi:10.1016/S0733-8627(20)30256-X. PMID 2201518.
  15. ^ Hendeles L (1993). "Selecting a decongestant". Pharmacotherapy. 13 (6 Pt 2): 129S–134S, discussion 143S–146S. doi:10.1002/j.1875-9114.1993.tb02781.x. PMID 7507590.
  16. ^ Barkholtz HM, Hadzima R, Miles A (July 2023). "Pharmacology of R-(-)-Methamphetamine in Humans: A Systematic Review of the Literature". ACS Pharmacol Transl Sci. 6 (7): 914–924. doi:10.1021/acsptsci.3c00019. PMC 10353062. PMID 37470013.
  17. ^ Schmitt KC, Reith ME (February 2010). "Regulation of the dopamine transporter: aspects relevant to psychostimulant drugs of abuse". Ann N Y Acad Sci. 1187: 316–340. doi:10.1111/j.1749-6632.2009.05148.x. PMID 20201860.
  18. ^ Meyer MR (October 2016). "New psychoactive substances: an overview on recent publications on their toxicodynamics and toxicokinetics". Arch Toxicol. 90 (10): 2421–2444. Bibcode:2016ArTox..90.2421M. doi:10.1007/s00204-016-1812-x. PMID 27665567.
  19. ^ a b Blough B (July 2008). "Dopamine-releasing agents" (PDF). In Trudell ML, Izenwasser S (eds.). Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. pp. 305–320. ISBN 978-0-470-11790-3. OCLC 181862653. OL 18589888W.
  20. ^ Gavai AK, Bouzembrak Y, van den Bulk LM, Liu N, van Overbeeke LF, van den Heuvel LJ, et al. (December 2021). "Artificial intelligence to detect unknown stimulants from scientific literature and media reports". Food Control. 130: 108360. doi:10.1016/j.foodcont.2021.108360. ISSN 0956-7135.
  21. ^ a b c Costa VM, Grando LG, Milandri E, Nardi J, Teixeira P, Mladěnka P, et al. (November 2022). "Natural Sympathomimetic Drugs: From Pharmacology to Toxicology". Biomolecules. 12 (12): 1793. doi:10.3390/biom12121793. PMC 9775352. PMID 36551221.
  22. ^ a b c Rothman RB, Baumann MH (December 2005). "Targeted screening for biogenic amine transporters: potential applications for natural products". Life Sci. 78 (5): 512–518. doi:10.1016/j.lfs.2005.09.001. PMID 16202429.
  23. ^ a b c d Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, et al. (October 2003). "In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates". J Pharmacol Exp Ther. 307 (1): 138–145. doi:10.1124/jpet.103.053975. PMID 12954796.
  24. ^ Gainetdinov RR, Hoener MC, Berry MD (July 2018). "Trace Amines and Their Receptors". Pharmacol Rev. 70 (3): 549–620. doi:10.1124/pr.117.015305. PMID 29941461.
  25. ^ Ilipilla G, Arnold LE (23 May 2024). "The role of adrenergic neurotransmitter reuptake inhibitors in the ADHD armamentarium". Expert Opinion on Pharmacotherapy. 25 (8): 945–956. doi:10.1080/14656566.2024.2369197. ISSN 1465-6566. PMID 38900676.
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