Levomethamphetamine

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.[note 2]

Levomethamphetamine
INN: Levmetamfetamine
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
  • (R)-N-methyl-1-phenyl-propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard100.046.974
Chemical and physical data
FormulaC10H15N
Molar mass149.23 g·mol−1
3D model (JSmol)
  • N([C@@H](Cc1ccccc1)C)C
  • InChI=1S/C10H15N/c1-9(11-2)8-10-6-4-3-5-7-10/h3-7,9,11H,8H2,1-2H3/t9-/m1/s1 checkY
  • Key:MYWUZJCMWCOHBA-SECBINFHSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Pharmacology

Levomethamphetamine crosses the blood-brain-barrier and acts as a norepinephrine transporter inhibitor[4] and TAAR1 agonist,[5] 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.[4][6]It does not possess the same potential for euphoria or addiction that dextromethamphetamine possesses.[4][6][7][8] Among its physiological effects are the vasoconstriction that makes it useful for nasal decongestion.[9] 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 article: Selegiline

Levomethamphetamine is an active metabolite of the antiparkinson's drug selegiline.[10] Selegiline, a selective monoamine oxidase B (MAOB) inhibitor at low doses,[note 3] is also metabolized into levomethamphetamine and levoamphetamine.[11][12] This has caused users to test positive for amphetamines.[13][14]

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.[15][16]

Side effects

When the nasal decongestant is taken in excess, levomethamphetamine has potential side effects resembling those of other sympathomimetic drugs; these effects include hypertension (elevated blood pressure), tachycardia (rapid heart rate), nausea, stomach cramps, dizziness, headache, sweating, muscle tension, and tremors. Central side effects may include anxiety, insomnia, and loss of appetite.

Non-medicinal usage

In a study of the psychoactive effects of levomethamphetamine, the intravenous administration of 0.5 mg/kg (but not 0.25 mg/kg) in recreational methamphetamine users produced scores of "drug liking" (pleasure and satisfaction with the drug) similar to racemic methamphetamine, but the effects were shorter lived. The study did not test the oral administration of levomethamphetamine. 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.[7] During the 1900s Methedrine was the brand name for racemic methamphetamine which consisted of a 50:50 mixture of both the levo and dextro enantiomers.

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.[17][18]

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.[19]

Notes
  1. Other names include l-methamphetamine, levodesoxyephedrine, l-desoxyephedrine, levmetamfetamine (INN and USAN).
  2. The active ingredient in some OTC inhalers in the United States is listed as levmetamfetamine, the INN and USAN of levomethamphetamine.[2][3]
  3. 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. Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P, et al. (October 2006). "Human pharmacology of the methamphetamine stereoisomers". Clinical Pharmacology and Therapeutics. 80 (4): 403–420. doi:10.1016/j.clpt.2006.06.013. PMID 17015058. S2CID 19072636.
  2. "CFR Title 21: Drugs for Human Use: Part 341 -- Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use". United States Food and Drug Administration. April 2015. Archived from the original on 18 September 2015. Retrieved 7 March 2016. Topical nasal decongestants --(i) For products containing levmetamfetamine identified in 341.20(b)(1) when used in an inhalant dosage form. The product delivers in each 800 milliliters of air 0.04 to 0.150 milligrams of levmetamfetamine.
  3. "Levomethamphetamine". PubChem. National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2 January 2014.
  4. Pauly RC, Bhimani RV, Li JX, Blough BE, Landavazo A, Park J (March 2023). "Distinct Effects of Methamphetamine Isomers on Limbic Norepinephrine and Dopamine Transmission in the Rat Brain". ACS Chemical Neuroscience: acschemneuro.2c00689. doi:10.1021/acschemneuro.2c00689. PMID 36976755.
  5. "Levmetamfetamine". PubChem. National Center for Biotechnology Information, U.S. National Library of Medicine. Archived from the original on 18 October 2014. Retrieved 17 October 2014.
  6. Melega WP, Cho AK, Schmitz D, Kuczenski R, Segal DS (February 1999). "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. PMID 9918585.
  7. Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P, et al. (October 2006). "Human pharmacology of the methamphetamine stereoisomers". Clinical Pharmacology and Therapeutics. 80 (4): 403–420. doi:10.1016/j.clpt.2006.06.013. PMID 17015058. S2CID 19072636.
  8. Kuczenski R, Segal DS, Cho AK, Melega W (February 1995). "Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine". The Journal of Neuroscience. 15 (2): 1308–1317. doi:10.1523/jneurosci.15-02-01308.1995. PMC 6577819. PMID 7869099.
  9. Pray SW. "Nonprescription Products to Avoid With Hypertension". uspharmacist.com. Archived from the original on 30 October 2014. Retrieved 17 October 2014. 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/levmetamfetamine. 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.
  10. EP 0344675, Hajicek J, Hrbata J, Pihera P, Brunova B, Ferenc M, Krepelka J, Kvapil L, Pospisil J, "Method for the production of selegiline hydrochloride.", published 6 December 1989, assigned to Spofa Vereinigte Pharma Werke.
  11. Kalász H, Magyar K, Szőke É, Adeghate E, Adem A, Hasan MY, et al. (1 January 2014). "Metabolism of selegiline [(-)-deprenyl)]". Current Medicinal Chemistry. 21 (13): 1522–1530. doi:10.2174/0929867321666131218094352. PMID 24350849.
  12. Magyar K (1 January 2011). "The pharmacology of selegiline". International Review of Neurobiology. 100: 65–84. doi:10.1016/B978-0-12-386467-3.00004-2. ISBN 9780123864673. PMID 21971003.
  13. Cody JD (December 1993). "Metabolic Precursors to Amphetamine and Methamphetamine". Forensic Science Review. 5 (2): 109–127. PMID 26270078.
  14. Cody JT (May 2002). "Precursor medications as a source of methamphetamine and/or amphetamine positive drug testing results". Journal of Occupational and Environmental Medicine. 44 (5): 435–450. doi:10.1097/00043764-200205000-00012. PMID 12024689. S2CID 44614179.
  15. Tabakman R, Lecht S, Lazarovici P (January 2004). "Neuroprotection by monoamine oxidase B inhibitors: a therapeutic strategy for Parkinson's disease?". BioEssays. 26 (1): 80–90. doi:10.1002/bies.10378. PMID 14696044.
  16. Kong P, Zhang B, Lei P, Kong X, Zhang S, Li D, Zhang Y (1 January 2015). "Neuroprotection of MAO-B inhibitor and dopamine agonist in Parkinson disease". International Journal of Clinical and Experimental Medicine. 8 (1): 431–439. PMC 4358469. PMID 25785014.
  17. "Mexico's precursor chemical controls: Emergence of less potent types of methamphetamine in the United States". ResearchGate. Retrieved 21 February 2023. {{cite web}}: Check |archive-url= value (help)CS1 maint: url-status (link)
  18. "Army Secures 1.2 Tons Of Methamphetamine In Cosalá, Sinaloa". Borderland Beat. 28 February 2023.
  19. DeGeorge M, Weber J (30 November 2012). "Methamphetamine Urine Toxicology: An In-depth Review". Practical Pain Management. Vertical Health LLC. Archived from the original on 13 February 2016. Retrieved 21 February 2016.
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