Chemistry:Levomethamphetamine

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Short description: Nasal decongestant and optical isomer of methamphetamine
Levomethamphetamine
INN: Levmetamfetamine
Levomethamphetamine.svg
(R)-methamphetamine-based-on-xtal-3D-bs-17.png
Clinical data
Routes of
administration		Medical: Inhalation (nasal)
Recreational: Oral, intravenous, insufflation, inhalation, suppository
Legal status
Legal status
Pharmacokinetic data
MetabolismHepatic
Elimination half-life13 - 15 hours[1]
ExcretionRenal
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC10H15N
Molar mass149.23 g·mol−1
3D model (JSmol)
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Levomethamphetamine[note 1] is the levorotatory (L-enantiomer) form of methamphetamine. Levomethamphetamine is a sympathomimetic vasoconstrictor that is the active ingredient in some over-the-counter (OTC) nasal decongestant inhalers in the United States.

Pharmacology

Pharmacodynamics

Levomethamphetamine crosses the blood-brain-barrier and acts as a norepinephrine transporter inhibitor[2] and TAAR1 agonist,[3] functioning as a selective norepinephrine releasing agent (with limited effects on the release of dopamine), thus levomethamphetamine affects the central nervous system, although its effects are qualitatively distinct relative to those of dextromethamphetamine.[2][4] It does not possess the same potential for euphoria or addiction that dextromethamphetamine possesses.[2][4][5][6] Among its physiological effects are the vasoconstriction that makes it useful for nasal decongestion.[7]

Pharmacokinetics

The elimination half-life of levomethamphetamine is between 13.3 and 15 hours, whereas dextromethamphetamine has a half-life of about 10.5 hours.[1]

Selegiline

Main page: Biology:Selegiline

Levomethamphetamine is an active metabolite of the antiparkinson's drug selegiline.[8] Selegiline, a selective monoamine oxidase B (MAOB) inhibitor at low doses,[note 2] is also metabolized into levomethamphetamine and levoamphetamine.[9][10] This has caused users to test positive for amphetamines.[11][12]

Selegiline itself has neuroprotective and neuro-rescuing effects, but concern over the resulting levomethamphetamine's neurotoxicity led to development of alternative MAOB inhibitors, such as rasagiline, that do not produce toxic metabolites.[13][14]

Side effects

When the nasal decongestant is taken in excess, levomethamphetamine has potential side effects. These would be similar to those of other decongestants.

Non-medicinal usage

As of 2006, there were no studies demonstrating "drug liking" scores of oral levomethamphetamine that are similar to racemic methamphetamine or dextromethamphetamine in either recreational users or medicinal users.[5]

In recent years, tighter controls in Mexico on certain methamphetamine precursors like ephedrine and pseudoephedrine has led to a greater percentage of illicit meth from Mexican drug cartels consisting of a higher ratio of levomethamphetamine to dextromethamphetamine within batches of racemic meth.[15][16]

Detection in body fluids

Levomethamphetamine can register on urine drug screens as either methamphetamine, amphetamine, or both, depending on the subject's metabolism and dosage. L-methamphetamine metabolizes completely into L-amphetamine after a period of time.[17]

Notes

  1. ↑ Other names include levmetamfetamine (INN), l-methamphetamine, levodesoxyephedrine, and l-desoxyephedrine.
  2. ↑ It is a selective MAOB inhibitor at normal clinical doses. MAOB is an enzyme that metabolizes dopamine, the neurotransmitter deficient in Parkinson's Syndrome.

References

  1. ↑ 1.0 1.1 "Human pharmacology of the methamphetamine stereoisomers". Clinical Pharmacology and Therapeutics 80 (4): 403–420. October 2006. doi:10.1016/j.clpt.2006.06.013. PMID 17015058. 
  2. ↑ 2.0 2.1 2.2 "Distinct Effects of Methamphetamine Isomers on Limbic Norepinephrine and Dopamine Transmission in the Rat Brain". ACS Chemical Neuroscience: acschemneuro.2c00689. March 2023. doi:10.1021/acschemneuro.2c00689. PMID 36976755. 
  3. ↑ "Levmetamfetamine". PubChem. National Center for Biotechnology Information, U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?q=all&cid=36604#x291. 
  4. ↑ 4.0 4.1 "l-methamphetamine pharmacokinetics and pharmacodynamics for assessment of in vivo deprenyl-derived l-methamphetamine". The Journal of Pharmacology and Experimental Therapeutics 288 (2): 752–758. February 1999. PMID 9918585. 
  5. ↑ 5.0 5.1 "Human pharmacology of the methamphetamine stereoisomers". Clinical Pharmacology and Therapeutics 80 (4): 403–420. October 2006. doi:10.1016/j.clpt.2006.06.013. PMID 17015058. 
  6. ↑ "Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine". The Journal of Neuroscience 15 (2): 1308–1317. February 1995. doi:10.1523/jneurosci.15-02-01308.1995. PMID 7869099. 
  7. ↑ Pray SW. "Nonprescription Products to Avoid With Hypertension". uspharmacist.com. http://www.uspharmacist.com/content/d/consult_your_pharmacist/c/19370/. "Topical Nasal Decongestants
    Most topical nasal decongestants also carry the warning against unsupervised use with hypertension. This includes oxymetazoline (e.g., Afrin), phenylephrine (e.g., Neo-Synephrine), naphazoline (e.g., Privine), and l-desoxyephedrine/levomethamphetamine. When hypertensive patients request a nasal decongestant, the pharmacist can recommend several alternatives. Propylhexedrine (e.g., Benzedrex Inhaler) is not required to carry a warning against unsupervised use with hypertension and may be effective. Another option is the nasal strip (e.g., Breathe Right). When properly applied, the strip can open the nostrils slightly, and perhaps sufficiently to allow the patient to breathe without use of a pharmacologically active ingredient."     
  8. ↑ Hajicek J, Hrbata J, Pihera P, Brunova B, Ferenc M, Krepelka J, Kvapil L, Pospisil J, "Method for the production of selegiline hydrochloride.", EP patent 0344675, published 6 December 1989, assigned to Spofa Vereinigte Pharma Werke.
  9. ↑ "Metabolism of selegiline [(-)-deprenyl)]". Current Medicinal Chemistry 21 (13): 1522–1530. 2014-01-01. doi:10.2174/0929867321666131218094352. PMID 24350849. 
  10. ↑ "The pharmacology of selegiline". International Review of Neurobiology 100: 65–84. 2011-01-01. doi:10.1016/B978-0-12-386467-3.00004-2. ISBN 9780123864673. PMID 21971003. 
  11. ↑ "Metabolic Precursors to Amphetamine and Methamphetamine". Forensic Science Review 5 (2): 109–127. December 1993. PMID 26270078. 
  12. ↑ "Precursor medications as a source of methamphetamine and/or amphetamine positive drug testing results". Journal of Occupational and Environmental Medicine 44 (5): 435–450. May 2002. doi:10.1097/00043764-200205000-00012. PMID 12024689. 
  13. ↑ "Neuroprotection by monoamine oxidase B inhibitors: a therapeutic strategy for Parkinson's disease?". BioEssays 26 (1): 80–90. January 2004. doi:10.1002/bies.10378. PMID 14696044. 
  14. ↑ "Neuroprotection of MAO-B inhibitor and dopamine agonist in Parkinson disease". International Journal of Clinical and Experimental Medicine 8 (1): 431–439. 2015-01-01. PMID 25785014. 
  15. ↑ "Mexico's precursor chemical controls: Emergence of less potent types of methamphetamine in the United States". https://www.researchgate.net/publication/232931104. 
  16. ↑ "Army Secures 1.2 Tons Of Methamphetamine In Cosalá, Sinaloa". Borderland Beat. 28 February 2023. http://www.borderlandbeat.com/2023/02/army-secures-12-tons-of-methamphetamine.html?m=1. 
  17. ↑ "Methamphetamine Urine Toxicology: An In-depth Review". Practical Pain Management. Vertical Health LLC. 30 November 2012. http://www.practicalpainmanagement.com/treatments/pharmacological/non-opioids/methamphetamine-urine-toxicology-depth-review. 



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