View source for Levomethamphetamine

{{Short description|Topical nasal decongestant}}
{{Use dmy dates|date=March 2014}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = verified
| INN = Levmetamfetamine
| verifiedrevid = 608094053
| image = Levomethamphetamine.svg
| width = 175px
| image2 = (R)-methamphetamine-based-on-xtal-3D-bs-17.png
| width2 = 225px

<!-- Clinical data -->| tradename = Vicks VapoInhaler, Everclear Inhaler, others
| routes_of_administration = ''Medical'': [[Intranasal]]<br />''Recreational'': [[Oral administration|By mouth]], [[intravenous]], [[insufflation]], [[inhalation]], [[suppository]]
| class = [[Norepinephrine releasing agent]]; [[Decongestant]]

<!-- Legal status -->| legal_AU = S8
| legal_BR = F2
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2024-05-28 |title=RDC Nº 877 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 877 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-da-diretoria-colegiada-anvisa-n-877-de-28-de-maio-de-2024-562758149 |url-status=live |archive-url=https://web.archive.org/web/20240925040323/https://www.in.gov.br/en/web/dou/-/resolucao-da-diretoria-colegiada-anvisa-n-877-de-28-de-maio-de-2024-562758149 |archive-date=2024-09-25 |access-date=2024-09-25 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2024-05-28}}</ref>
| legal_CA = Schedule I
| legal_UK = Class A
| legal_US = Schedule II
| legal_US_comment = and for specific formulations [[Over-the-counter drug|OTC]]
| legal_UN = Psychotropic Schedule II
| legal_DE = Anlage II
| legal_status = <!-- Pharmacokinetic data -->
| bioavailability = [[Oral administration|Oral]]: ~100%<ref name="BarkholtzHadzimaMiles2023" /><ref name="LiLopezGalloway2010" />
| protein_bound = 
| metabolism = [[Liver]] ([[CYP2D6]])<ref name="KraemerMaurer2002" /><ref name="ScheininAnttilaDahl1998" />
| metabolites = [[Levoamphetamine]]<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /><ref name="LiLopezGalloway2010" />
| elimination_half-life = 10–15 hours<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /><ref name="LiLopezGalloway2010" />
| excretion = [[Urine]] (41–49% unchanged, 2–3% as [[levoamphetamine]])<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /><ref name="LiLopezGalloway2010" />

<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 33817-09-3
| PubChem = 36604
| DrugBank = DB09571
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 33634
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = Y24T9BT2Q2
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02291
| synonyms = {{nowrap|''l''-methamphetamine}}; {{nowrap|(-)-methamphetamine}}; {{nowrap|(''R'')-methamphetamine}}; {{nowrap|(''R'')-(-)-methamphetamine}}; {{nowrap|''l''-desoxyephedrine}}; levodesoxyephedrine

<!-- Chemical data -->| IUPAC_name = (''R'')-''N''-methyl-1-phenylpropan-2-amine
| C = 10
| H = 15
| N = 1
| chirality = [[Levorotatory]] [[enantiomer]]
| SMILES = N([C@@H](Cc1ccccc1)C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H15N/c1-9(11-2)8-10-6-4-3-5-7-10/h3-7,9,11H,8H2,1-2H3/t9-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MYWUZJCMWCOHBA-SECBINFHSA-N
}}

'''Levomethamphetamine'''{{Efn|'''Levomethamphetamine''' has several synonyms that are frequently used in medical and scientific literature. Prominent synonyms include '''(''R'')-methamphetamine''', '''''l''-methamphetamine''', and '''(-)-methamphetamine'''. '''Levmetamfetamine''' is the International Nonproprietary Name used for pharmaceutical product labelling; '''''l''-desoxyephedrine''' is an older name for the pharmaceutical product.}} ([[International Nonproprietary Name|INN]]: '''levmetamfetamine''') is an [[optical isomer]] of [[methamphetamine]] primarily used as a [[Topical decongestant|topical nasal decongestant]].<ref name="BarkholtzHadzimaMiles2023">{{cite journal |vauthors=Barkholtz HM, Hadzima R, Miles A |date=July 2023 |title=Pharmacology of R-(-)-Methamphetamine in Humans: A Systematic Review of the Literature |journal=ACS Pharmacol Transl Sci |volume=6 |issue=7 |pages=914–924 |doi=10.1021/acsptsci.3c00019 |pmc=10353062 |pmid=37470013}}</ref> Levomethamphetamine is used to treat nasal congestion from [[Allergic rhinitis|allergies]] and the [[common cold]].<ref>{{Cite web |date=June 7, 2023 |title=Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use |url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=341.20 |url-status=dead |archive-url=https://web.archive.org/web/20230706041627/https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=341.20 |archive-date=6 July 2023 |website=[[FDA]]}}</ref> It was first used medically as decongestant beginning in 1958 and has been used for such purposes, primarily in the United States, since then.<ref name="WessonSmithMorgan1986" />

==Medical uses==
Levomethamphetamine is used to treat nasal congestion related to the common cold and allergic rhinitis. It is available in the form of an inhaler containing 50{{nbsp}}mg total per inhaler and delivering between 0.04 and 0.15{{nbsp}}mg of the drug per inhalation.<ref name="BarkholtzHadzimaMiles2023" /> Inhalers with a total of 113{{nbsp}}mg levomethamphetamine were previously marketed in the United States, but the total amount was eventually reduced to 50{{nbsp}}mg.<ref name="BarkholtzHadzimaMiles2023" />

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

==Pharmacology==

===Pharmacodynamics===
{| class="wikitable floatright" style="font-size:small;"
|+ {{Nowrap|Monoamine release of levomethamphetamine and related agents ({{Abbrlink|EC<sub>50</sub>|Half maximal effective concentration}}, nM)}}
|-
! Compound !! data-sort-type="number" | {{abbrlink|NE|Norepinephrine}} !! data-sort-type="number" | {{abbrlink|DA|Dopamine}} !! data-sort-type="number" | {{abbrlink|5-HT|Serotonin}} !! Ref
|-
| [[Phenethylamine]] || 10.9 || 39.5 || >10,000 || <ref name="ReithBLoughHong2015">{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug and Alcohol Dependence | volume = 147 | issue =  | pages = 1–19 | date = February 2015 | pmid = 25548026 | pmc = 4297708 | doi = 10.1016/j.drugalcdep.2014.12.005 }}</ref><ref name="Forsyth2012" /><ref name="Blough2008" />
|-
| [[Amphetamine]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}
|-
| {{nbsp}}{{nbsp}}[[Dextroamphetamine|{{Small|D}}-Amphetamine]] || 6.6–7.2 || 5.8–24.8 || 698–1,765 || <ref name="RothmanBaumannDersch2001" /><ref name="BaumannPartillaLehner2013">{{cite journal | vauthors = Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW | title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products | journal = Neuropsychopharmacology | volume = 38 | issue = 4 | pages = 552–562 | year = 2013 | pmid = 23072836 | pmc = 3572453 | doi = 10.1038/npp.2012.204 }}</ref>
|-
| {{nbsp}}{{nbsp}}[[Levoamphetamine|{{Small|L}}-Amphetamine]] || 9.5 || 27.7 || {{abbr|ND|No data}} || <ref name="Forsyth2012">{{cite journal | last=Forsyth | first=Andrea N | title=Synthesis and Biological Evaluation of Rigid Analogues of Methamphetamines | website=ScholarWorks@UNO | date=22 May 2012 | url=https://scholarworks.uno.edu/td/1436/ | access-date=4 November 2024}}</ref><ref name="Blough2008">{{cite book | vauthors = Blough B | chapter = Dopamine-releasing agents | veditors = Trudell ML, Izenwasser S | title = Dopamine Transporters: Chemistry, Biology and Pharmacology | pages = 305–320 | date = July 2008 | isbn = 978-0-470-11790-3 | oclc = 181862653 | ol = OL18589888W | publisher = Wiley | location = Hoboken [NJ] | doi = | url = https://books.google.com/books?id=QCagLAAACAAJ | chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}</ref>
|-
| [[Racephedrine]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}
|-
| {{nbsp}}{{nbsp}}[[Ephedrine]] ({{Small|D}}-) || 43.1–72.4 || 236–1,350 || >10,000 || <ref name="RothmanBaumannDersch2001" />
|-
| {{nbsp}}{{nbsp}}{{Small|L}}-Ephedrine || 218 || 2,104 || >10,000 || <ref name="RothmanBaumannDersch2001" /><ref name="RothmanPartillaRoth2003">{{cite journal | vauthors = Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA | s2cid = 19015584 | title = In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates | journal = J. Pharmacol. Exp. Ther. | volume = 307 | issue = 1 | pages = 138–45 | year = 2003 | pmid = 12954796 | doi = 10.1124/jpet.103.053975 }}</ref>
|-
| [[Methamphetamine]] || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}
|-
| {{nbsp}}{{nbsp}}[[Dextromethamphetamine|{{Small|D}}-Methamphetamine]] || 12.3–13.8 || 8.5–24.5 || 736–1,292 || <ref name="RothmanBaumannDersch2001" /><ref name="BaumannAyestasPartilla2012">{{cite journal | vauthors = Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV | title = The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue | journal = Neuropsychopharmacology | volume = 37 | issue = 5 | pages = 1192–1203 | year = 2012 | pmid = 22169943 | pmc = 3306880 | doi = 10.1038/npp.2011.304 }}</ref>
|-
| '''{{nbsp}}{{nbsp}}{{Small|L}}-Methamphetamine'''|| 28.5 || 416 || 4,640 || <ref name="RothmanBaumannDersch2001" />
|-
| Racemic pseudoephedrine || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}} || {{abbr|ND|No data}}
|-
| {{nbsp}}{{nbsp}}{{Small|D}}-Pseudoephedrine || 4,092 || 9,125 || >10,000 || <ref name="RothmanPartillaRoth2003" />
|-
| {{nbsp}}{{nbsp}}[[Pseudoephedrine]] ({{Small|L}}-) || 224 || 1,988 || >10,000 || <ref name="RothmanPartillaRoth2003" />
|-
| colspan="7" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' The smaller the value, the more strongly the drug releases the neurotransmitter. See also [[Monoamine releasing agent#Activity profiles|Monoamine releasing agent § Activity profiles]] for a larger table with more compounds. '''Refs:''' <ref name="RothmanBaumann2003" /><ref name="RothmanBaumann2006">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–1859 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = https://zenodo.org/record/1235860 }}</ref>
|}

Levomethamphetamine acts as a [[binding selectivity|selective]] [[norepinephrine releasing agent]].<ref name="RothmanBaumannDersch2001">{{cite journal | vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS | title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | journal = Synapse | volume = 39 | issue = 1 | pages = 32–41 | date = January 2001 | pmid = 11071707 | doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 | url = }}</ref><ref name="RothmanBaumann2003">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur J Pharmacol | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 | url = }}</ref><ref name="KohutJacobsRothman2017">{{cite journal | vauthors = Kohut SJ, Jacobs DS, Rothman RB, Partilla JS, Bergman J, Blough BE | title = Cocaine-like discriminative stimulus effects of "norepinephrine-preferring" monoamine releasers: time course and interaction studies in rhesus monkeys | journal = Psychopharmacology (Berl) | volume = 234 | issue = 23–24 | pages = 3455–3465 | date = December 2017 | pmid = 28889212 | pmc = 5747253 | doi = 10.1007/s00213-017-4731-5 | url = | quote = In the present experiments, two monoamine releasers, l-MA and PAL-329, were shown to produce cocaine-like discriminative-stimulus effects in monkeys, suggesting that they meet the above criteria. One of these compounds, l-MA, also has been shown to serve as a positive reinforcer in rodents (Yokel and Pickens 1973) and monkeys (Winger et al 1994), further confirming the overlap with behavioral effects of cocaine. Both compounds also exhibit an approximately 15-fold greater potency in releasing NE than DA, which may be therapeutically advantageous. For example, the subjective effects of l-MA in human studies are similar in some respects to those of d-MA. However, the subjective effects of the two isomers also differ in potentially important ways. While both l-MA and d-MA produce subjective ratings of "drug liking" and "good effects" in experienced stimulant users, only lMA produces concomitant ratings of bad or aversive drug effects (Mendelson et al 2006), a factor which may limit its abuse liability.}}</ref><ref name="MendelsonUemuraHarris2006">{{cite journal | vauthors = Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P, Everhart ET, Jones RT | title = Human pharmacology of the methamphetamine stereoisomers | journal = Clin Pharmacol Ther | volume = 80 | issue = 4 | pages = 403–420 | date = October 2006 | pmid = 17015058 | doi = 10.1016/j.clpt.2006.06.013 | url = | quote = The stereoisomers of methamphetamine produce markedly different dopamine, norepinephrine, and serotonin responses in various brain regions in rats.41,42 d-Methamphetamine (2 mg/kg) is more potent in releasing caudate dopamine than l-methamphetamine (12 and 18 mg/kg). By use of in vitro uptake and release assays, d-methamphetamine (50% effective concentration [EC50], 24.5 ± 2.1 nmol/L) was 17 times more potent in releasing dopamine than l-methamphetamine (EC50, 416 ± 20 nmol/L) and significantly more potent in blocking dopamine uptake (inhibition constant [Ki ], 114 ± 11 nm versus 4840 ± 178 nm).12,13}}</ref> The [[potency (pharmacology)|potencies]] of levomethamphetamine, [[levoamphetamine]], [[dextromethamphetamine]], and [[dextroamphetamine]] in terms of norepinephrine release ''[[in vitro]]'' and ''[[in vivo]]'' in rats are all similar.<ref name="HealSmithGosden2013">{{cite journal | vauthors = Heal DJ, Smith SL, Gosden J, Nutt DJ | title = Amphetamine, past and present--a pharmacological and clinical perspective | journal = J Psychopharmacol | volume = 27 | issue = 6 | pages = 479–496 | date = June 2013 | pmid = 23539642 | pmc = 3666194 | doi = 10.1177/0269881113482532 | url = }}</ref><ref name="NishinoKotorii2016">{{cite book | vauthors = Nishino S, Kotorii N | title=Narcolepsy: A Clinical Guide | edition=2nd | chapter=Modes of Action of Drugs Related to Narcolepsy: Pharmacology of Wake-Promoting Compounds and Anticataplectics | publisher=Springer International Publishing | publication-place=Cham | date=2016 | isbn=978-3-319-23738-1 | doi=10.1007/978-3-319-23739-8_22 | pages=307–329 | url = https://www.researchgate.net/publication/314626865 }}</ref><ref name="ZueSiemianZhu2019" /><ref name="KuczenskiSegalCho1995" /><ref name="RothmanBaumann2003" />

Conversely, whereas dextromethamphetamine and dextroamphetamine are relatively balanced [[norepinephrine–dopamine releasing agent|releasers of dopamine and norepinephrine]] ''in vitro'', levomethamphetamine is about 15- to 20-fold less [[potency (pharmacology)|potent]] in inducing dopamine release relative to norepinephrine release.<ref name="RothmanBaumann2003" /><ref name="KohutJacobsRothman2017" /><ref name="MendelsonUemuraHarris2006" /><ref name="RothmanBaumannDersch2001"/><ref name="ZueSiemianZhu2019">{{cite journal | vauthors = Xue Z, Siemian JN, Zhu Q, Blough BE, Li JX | title = Further pharmacological comparison of D-methamphetamine and L-methamphetamine in rats: abuse-related behavioral and physiological indices | journal = Behav Pharmacol | volume = 30 | issue = 5 | pages = 422–428 | date = August 2019 | pmid = 30480551 | pmc = 6529304 | doi = 10.1097/FBP.0000000000000453 | url = | quote = When considered with neurochemical data that l-MA is similarly potent in releasing norepinephrine (NE) but 15- to 20-fold less potent in releasing dopamine (DA), as compared to d-MA (Kuczenski et al., 1995; Melega et al., 1999), l-MA may appear to carry lower abuse liability than d-MA.}}</ref> Moreover, whereas levoamphetamine is about 3- to 5-fold less potent in terms of dopamine release than dextroamphetamine ''in vivo'', levomethamphetamine is dramatically less potent than dextromethamphetamine and substantially less potent than levoamphetamine in this regard.<ref name="NishinoKotorii2016" /><ref name="HealSmithGosden2013" /><ref name="KuczenskiSegalCho1995" />

In accordance with the findings of [[catecholamine]] release studies, levomethamphetamine is 2- to 10-fold or more less potent than dextromethamphetamine in terms of [[psychostimulant]]-like effects in rodents.<ref name="NishimuraTakahataKosugi2017">{{cite journal | vauthors = Nishimura T, Takahata K, Kosugi Y, Tanabe T, Muraoka S | title = Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles | journal = J Neural Transm (Vienna) | volume = 124 | issue = 5 | pages = 519–523 | date = May 2017 | pmid = 28213761 | pmc = 5399046 | doi = 10.1007/s00702-017-1694-y | url = | quote = There have been no studies directly comparing the pharmacodynamics and pharmacokinetics of the methamphetamine enantiomers in mice. It is often suggested that dmethamphetamine exerts more potent physiological and pharmacological effects than l-methamphetamine does, and that the stimulating effects exerted by l-methamphetamine on the central nervous system are 2–10 times less potent than those of d-methamphetamine (Mendelson et al. 2006). The results of the present study indicated that psychostimulant effects induced by l-methamphetamine are lower than those elicited by one-tenth the dose of d-methamphetamine. In addition, plasma pharmacokinetic parameters and striatal concentrations of methamphetamine following administration of l-methamphetamine at 10 mg/ kg (which did not induce psychomotor activity) were approximately 11 and 16 times as high, respectively, as those following administration of 1 mg/kg d-methamphetamine. Despite the fact that there are differentiable psycho-stimulating effects between two enantiomers, no significant difference in plasma pharmacokinetic parameters was detected at 1 mg/kg.}}</ref><ref name="SiemianXueBlough2017">{{cite journal | vauthors = Siemian JN, Xue Z, Blough BE, Li JX | title = Comparison of some behavioral effects of d- and l-methamphetamine in adult male rats | journal = Psychopharmacology (Berl) | volume = 234 | issue = 14 | pages = 2167–2176 | date = July 2017 | pmid = 28386698 | pmc = 5482751 | doi = 10.1007/s00213-017-4623-8 | url = }}</ref><ref name="PaulyBhimaniLi2023" /> For comparison, levoamphetamine is only 1- to 4-fold less potent than dextroamphetamine in its stimulating and [[positive reinforcement|reinforcing]] effects in monkeys and humans.<ref name="HealSmithGosden2013" /><ref name="SmithDavis1977" />

The effects of levomethamphetamine are qualitatively distinct relative to those of [[racemic mixture|racemic]] methamphetamine and dextromethamphetamine and it does not possess the same potential for [[euphoria]] or [[drug addiction|addiction]] that these drugs possess.<ref name="BarkholtzHadzimaMiles2023" /><ref name="PaulyBhimaniLi2023">{{cite journal | vauthors = Pauly RC, Bhimani RV, Li JX, Blough BE, Landavazo A, Park J | title = Distinct Effects of Methamphetamine Isomers on Limbic Norepinephrine and Dopamine Transmission in the Rat Brain | journal = ACS Chemical Neuroscience | pages = acschemneuro.2c00689 | date = March 2023 | pmid = 36976755 | doi = 10.1021/acschemneuro.2c00689 | s2cid = 257772503 }}</ref><ref name="MelegaChoSchmitz1999">{{cite journal |vauthors=Melega WP, Cho AK, Schmitz D, Kuczenski R, Segal DS |date=February 1999 |title=l-methamphetamine pharmacokinetics and pharmacodynamics for assessment of in vivo deprenyl-derived l-methamphetamine |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=288 |issue=2 |pages=752–758 |doi=10.1016/S0022-3565(24)38016-4 |pmid=9918585}}</ref><ref name="MendelsonUemuraHarris2006" /><ref name="KuczenskiSegalCho1995">{{cite journal | vauthors = Kuczenski R, Segal DS, Cho AK, Melega W | title = Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine | journal = The Journal of Neuroscience | volume = 15 | issue = 2 | pages = 1308–1317 | date = February 1995 | pmid = 7869099 | pmc = 6577819 | doi = 10.1523/jneurosci.15-02-01308.1995 | doi-access = free | quote = Consistent with our past results, in response to 2 mg/kg D-AMPH, mean caudate extracellular DA increased approximately 15-fold to a peak concentration of 688 ± 121 nM during the initial 20 min interval, then returned to baseline over the next 3 hr. Similarly, in response to 2 mg/kg D-METH, DA increased to a peak concentration of 648 ± 71 nM during the initial 20 min interval and then declined toward baseline. In contrast, in response to both 6 mg/kg L-AMPH and 12 mg/kg L-METH, peak DA concentrations (508 ± 51 and 287 ± 49 nM, respectively) were delayed to the second 20 min interval, before returning toward baseline. [...] Similar to our previous results, 2 mg/kg D-AMPH increased NE to a maximum of 29.3 ± 3.1 nM, about 20-fold over baseline, during the second 20 min interval. L-AMPH (6 mg/kg) produced a comparable effect, increasing NE concentrations to 32.0 ± 8.9 nM. In contrast, D-METH promoted an increase in NE to 12.0 ± 1.2 nM which was significantly lower than all other groups, whereas L-METH promoted an increase to 64.8 ± 4.9 nM, which was significantly higher than all other groups.}}</ref> In clinical studies, levomethamphetamine at oral doses of 1 to 10{{nbsp}}mg has been found not to affect subjective drug responses, [[heart rate]], [[blood pressure]], [[body temperature|core temperature]], [[electrocardiography]], [[respiration rate]], [[oxygen saturation]], or other clinical parameters.<ref name="BarkholtzHadzimaMiles2023" /><ref name="LiLopezGalloway2010">{{cite journal | vauthors = Li L, Lopez JC, Galloway GP, Baggott MJ, Everhart T, Mendelson J | title = Estimating the intake of abused methamphetamines using experimenter-administered deuterium labeled R-methamphetamine: selection of the R-methamphetamine dose | journal = Ther Drug Monit | volume = 32 | issue = 4 | pages = 504–7 | date = August 2010 | pmid = 20592647 | pmc = 3040572 | doi = 10.1097/FTD.0b013e3181db82f2 | url = }}</ref> As such, doses of levomethamphetamine of less than or equal to 10{{nbsp}}mg have no significant physiological or subjective effects.<ref name="BarkholtzHadzimaMiles2023" /><ref name="LiLopezGalloway2010" /> However, higher doses of levomethamphetamine, for instance 0.25 to 0.5{{nbsp}}mg/kg (mean doses of ~18–37{{nbsp}}mg) [[intravenous administration|intravenously]], have been reported to produce significant [[pharmacology|pharmacological]] effects, including increased heart rate and blood pressure, increased respiration rate, and subjective effects like [[substance intoxication|intoxication]] and [[drug liking]].<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /> On the other hand, in contrast to dextromethamphetamine, levomethamphetamine also produces subjective "bad" or aversive drug effects.<ref name="KohutJacobsRothman2017" /><ref name="MendelsonUemuraHarris2006" /> Among the physiological effects of levomethamphetamine is [[vasoconstrictor|vasoconstriction]], which makes it useful for nasal decongestion.<ref name="Pray2010">{{cite web | vauthors = Pray SW | title=Nonprescription Products to Avoid With Hypertension | work=uspharmacist.com | date=19 February 2010 | access-date=17 October 2014 | url=https://www.uspharmacist.com/article/nonprescription-products-to-avoid-with-hypertension | quote=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. | archive-url=https://web.archive.org/web/20141030183542/http://www.uspharmacist.com/content/d/consult_your_pharmacist/c/19370/ | archive-date=30 October 2014 | url-status=live }}</ref>

For comparison to levomethamphetamine, 5 to 60{{nbsp}}mg oral doses of the related drug levoamphetamine have been used clinically and have been reported to produce significant pharmacological effects, for instance on [[wakefulness-promoting agent|wakefulness]] and [[mood (psychology)|mood]].<ref name="SilverstoneWells1980">{{cite book | vauthors = Silverstone T, Wells B | title=Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects | chapter=Clinical Psychopharmacology of Amphetamine and Related Compounds | publisher=CRC Press | date=1980 | isbn=978-0-429-27984-3 | doi=10.1201/9780429279843-10 | pages=147–160 | quote = A comparison of dextroamphetamine and levoamphetamine revealed that the dextrorotatory isomer was the more potent in elevating mood in normal subjects, being at least twice as potent as the levo form.35 [...] Narcolepsy was one of the first conditions to be treated successfully with amphetamine3 and remains one of the few (some would say the only) clinical indications for its use. While the required oral dose of dextroamphetamine (Dexedrine®) ranges from 5 to 120 mg/day, most patients respond to 10 mg two to four times daily. [...] The closely related compound methylphenidate (Ritalin®), 20 mg two to four times daily, has been shown to be as effective as dextroamphetamine but with less likelihood of causing side effects.61 The same is true of levoamphetamine.62 [...] Nevertheless, as amphetamine has an action on dopaminergic pathways it was considered worthwhile to examine the effects of amphetamine under controlled conditions.95 Twenty patients, all on other anti-Parkinsonian drugs, were studied. There was some subjective improvement in a proportion (less than half) of the patients when they received either dextroamphetamine or levoamphetamine, but there was little objective improvement. The authors remarked that amphetamine was unlikely to have worked anyway in Parkinson's disease as it acts mainly by releasing dopamine and noradrenaline from presynaptic neurons; as the underlying pathology involves a reduction of presynaptic dopamine, there would be insufficient dopamine for amphetamine to release.}}</ref><ref name="ParkesFenton1973">{{cite journal | vauthors = Parkes JD, Fenton GW | title = Levo(-) amphetamine and dextro(+) amphetamine in the treatment of narcolepsy | journal = J Neurol Neurosurg Psychiatry | volume = 36 | issue = 6 | pages = 1076–81 | date = December 1973 | pmid = 4359162 | pmc = 1083612 | doi = 10.1136/jnnp.36.6.1076 | url = }}</ref><ref name="ParkesTarsyMarsden1975">{{cite journal | vauthors = Parkes JD, Tarsy D, Marsden CD, Bovill KT, Phipps JA, Rose P, Asselman P | title = Amphetamines in the treatment of Parkinson's disease | journal = J Neurol Neurosurg Psychiatry | volume = 38 | issue = 3 | pages = 232–7 | date = March 1975 | pmid = 1097600 | pmc = 491901 | doi = 10.1136/jnnp.38.3.232 | url = }}</ref><ref name="SmithDavis1977">{{cite journal | vauthors = Smith RC, Davis JM | title = Comparative effects of d-amphetamine, l-amphetamine, and methylphenidate on mood in man | journal = Psychopharmacology (Berl) | volume = 53 | issue = 1 | pages = 1–12 | date = June 1977 | pmid = 407607 | doi = 10.1007/BF00426687 | url = | quote = [...] the 2:1 ratio of d- and l-AMP effects on euphoric mood is very similar to the ratios (1.3:1 to 2.1:1) which have been reported for the efficacy of amphetamine isomers on other classes of behavior in man—for example, the activation of psychosis and the treatment of hyperkinetic children (see Table 1). [...] Table 1. Some previous studies comparing effects of d-amphetamine, l-amphetamine, and methylphenidate in man. [...]}}</ref>{{#tag:ref|Smith & Davis (1977) reviewed 11{{nbsp}}clinical studies of dextroamphetamine and levoamphetamine including doses and potency ratios in terms of a variety of psychological and behavioral effects.<ref name="SmithDavis1977" /> The summaries of these studies are in Table 1 of the paper.<ref name="SmithDavis1977" />|name=smith-davis-1977-review}}

In addition to its norepinephrine-releasing activity, levomethamphetamine  is also an [[agonist]] of the [[trace amine-associated receptor 1]] (TAAR1).<ref name="PubChem-TAAR1">{{cite web | work = PubChem | publisher = National Center for Biotechnology Information, U.S. National Library of Medicine | url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?q=all&cid=36604#x291 | title=Levmetamfetamine  | access-date=17 October 2014 | archive-url=https://web.archive.org/web/20141018010302/https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?q=all&cid=36604#x291 | archive-date=18 October 2014 | url-status=live }}</ref><ref name="SotnikovaCaronGainetdinov2009">{{cite journal | vauthors = Sotnikova TD, Caron MG, Gainetdinov RR | title = Trace amine-associated receptors as emerging therapeutic targets | journal = Mol Pharmacol | volume = 76 | issue = 2 | pages = 229–35 | date = August 2009 | pmid = 19389919 | pmc = 2713119 | doi = 10.1124/mol.109.055970 | url = | quote = Intriguingly, d- and l-amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), and other closely related compounds are also able to activate TAAR1 receptors in vitro as evidenced by cAMP stimulation in human embryonic kidney cells.}}</ref><ref name="ReeseNorimatsuGrandy2014">{{cite journal | vauthors = Reese EA, Norimatsu Y, Grandy MS, Suchland KL, Bunzow JR, Grandy DK | title = Exploring the determinants of trace amine-associated receptor 1's functional selectivity for the stereoisomers of amphetamine and methamphetamine | journal = J Med Chem | volume = 57 | issue = 2 | pages = 378–390 | date = January 2014 | pmid = 24354319 | doi = 10.1021/jm401316v | url = }}</ref>  Levomethamphetamine has also been found to act as a [[catecholaminergic activity enhancer]] (CAE), notably at much lower concentrations than its catecholamine releasing activity.<ref name="Knoll2001">{{cite journal | vauthors = Knoll J | title = Antiaging compounds: (-)deprenyl (selegeline) and (-)1-(benzofuran-2-yl)-2-propylaminopentane, [(-)BPAP], a selective highly potent enhancer of the impulse propagation mediated release of catecholamine and serotonin in the brain | journal = CNS Drug Rev | volume = 7 | issue = 3 | pages = 317–45 | date = 2001 | pmid = 11607046 | pmc = 6494119 | doi = 10.1111/j.1527-3458.2001.tb00202.x | url = }}</ref><ref name="Knoll1998">{{cite journal | vauthors = Knoll J | title = (-)Deprenyl (selegiline), a catecholaminergic activity enhancer (CAE) substance acting in the brain | journal = Pharmacol Toxicol | volume = 82 | issue = 2 | pages = 57–66 | date = February 1998 | pmid = 9498233 | doi = 10.1111/j.1600-0773.1998.tb01399.x | url = }}</ref><ref name="KnollMiklyaKnoll1996">{{cite journal | vauthors = Knoll J, Miklya I, Knoll B, Markó R, Kelemen K | title = (-)Deprenyl and (-)1-phenyl-2-propylaminopentane, [(-)PPAP], act primarily as potent stimulants of action potential-transmitter release coupling in the catecholaminergic neurons | journal = Life Sci | volume = 58 | issue = 10 | pages = 817–827 | date = 1996 | pmid = 8602114 | doi = 10.1016/0024-3205(96)00014-8 | url = }}</ref><ref name="KnollMiklya1994">{{cite journal | vauthors = Knoll J, Miklya I | title = Multiple, small dose administration of (-)deprenyl enhances catecholaminergic activity and diminishes serotoninergic activity in the brain and these effects are unrelated to MAO-B inhibition | journal = Arch Int Pharmacodyn Ther | volume = 328 | issue = 1 | pages = 1–15 | date = 1994 | pmid = 7893186 | doi = | url = }}</ref><ref name="HarsingTimarMiklya2023">{{cite journal |vauthors=Harsing LG, Timar J, Miklya I |date=August 2023 |title=Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline |journal=Int J Mol Sci |volume=24 |issue=17 |page=13334 |doi=10.3390/ijms241713334 |pmc=10487936 |pmid=37686140 |doi-access=free}}</ref> It is 1- to 10-fold less potent than selegiline but is 3- to 5-fold more potent than dextromethamphetamine in this action.<ref name="Knoll1998" /><ref name="KnollMiklyaKnoll1996" /><ref name="KnollMiklya1994" /> The CAE effects of such agents may be mediated by TAAR1 agonism.<ref name="HarsingKnollMiklya2022">{{cite journal | vauthors = Harsing LG, Knoll J, Miklya I | title = Enhancer Regulation of Dopaminergic Neurochemical Transmission in the Striatum | journal = Int J Mol Sci | volume = 23 | issue = 15 | date = August 2022 | page = 8543 | pmid = 35955676 | pmc = 9369307 | doi = 10.3390/ijms23158543 | doi-access = free | url = }}</ref><ref name="HarsingTimarMiklya2023" />

===Pharmacokinetics===
====Absorption====
The [[bioavailability]] of levomethamphetamine is approximately 100%.<ref name="BarkholtzHadzimaMiles2023" /><ref name="LiLopezGalloway2010" /> The [[Cmax (pharmacology)|peak]] levels of levomethamphetamine range from 3.3 to 31.4{{nbsp}}ng/mL with single oral doses of 1 to 10{{nbsp}}mg and from 65.4 to 125.9{{nbsp}}ng/mL with single [[intravenous administration|intravenous]] doses of 0.25 to 0.5{{nbsp}}mg/kg.<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /><ref name="LiEverhartJacob2010" /> The [[area-under-the-curve (pharmacokinetics)|area-under-the-curve]] (AUC) levels of levomethamphetamine range from 73.0 to 694.7{{nbsp}}ng⋅h/mL with single oral doses of 1 to 10{{nbsp}}mg and from 1,190.7 to 2,368.1{{nbsp}}mg/kg with single intravenous doses of 0.25 to 0.5{{nbsp}}mg/kg.<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /><ref name="LiEverhartJacob2010">{{cite journal | vauthors = Li L, Everhart T, Jacob Iii P, Jones R, Mendelson J | title = Stereoselectivity in the human metabolism of methamphetamine | journal = Br J Clin Pharmacol | volume = 69 | issue = 2 | pages = 187–192 | date = February 2010 | pmid = 20233182 | pmc = 2824480 | doi = 10.1111/j.1365-2125.2009.03576.x | url = }}</ref>

====Distribution====
The [[volume of distribution]] of levomethamphetamine is 288.5 to 315.5{{nbsp}}L or 4.15 to 4.17{{nbsp}}L/kg.<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /><ref name="LiLopezGalloway2010" />

====Metabolism====
The pharmacokinetics of levomethamphetamine generated as a [[metabolite]] from [[selegiline]] have been found to be significantly different in [[CYP2D6]] [[poor metabolizer]]s versus [[extensive metabolizer]]s.<ref name="KraemerMaurer2002">{{cite journal |vauthors=Kraemer T, Maurer HH |date=April 2002 |title=Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives |journal=Ther Drug Monit |volume=24 |issue=2 |pages=277–89 |doi=10.1097/00007691-200204000-00009 |pmid=11897973}}</ref><ref name="ScheininAnttilaDahl1998">{{cite journal | vauthors = Scheinin H, Anttila M, Dahl ML, Karnani H, Nyman L, Taavitsainen P, Pelkonen O, Bertilsson L | title = CYP2D6 polymorphism is not crucial for the disposition of selegiline | journal = Clin Pharmacol Ther | volume = 64 | issue = 4 | pages = 402–411 | date = October 1998 | pmid = 9797797 | doi = 10.1016/S0009-9236(98)90071-6 | url = }}</ref> [[Area-under-the-curve (pharmacokinetics)|Area-under-the-curve]] (AUC) levels of levomethamphetamine were 46% higher and its [[elimination half-life]] was 33% longer in CYP2D6 poor metabolizers compared to extensive metabolizers.<ref name="KraemerMaurer2002" /><ref name="ScheininAnttilaDahl1998" /> These findings suggest that CYP2D6 may be significantly involved in the metabolism of levomethamphetamine.<ref name="KraemerMaurer2002" /><ref name="ScheininAnttilaDahl1998" />

Levomethamphetamine is [[drug metabolism|metabolized]] into [[levoamphetamine]] in small amounts.<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /><ref name="LiLopezGalloway2010" />

====Elimination====
Levomethamphetamine is [[excretion|excreted]] in [[urine]] 40.8 to 49.0% as unchanged levomethamphetamine and 2.1 to 3.3% as [[levoamphetamine]].<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /><ref name="LiLopezGalloway2010" /> Levomethamphetamine can register on urine [[drug test]]s as either methamphetamine, amphetamine, or both, depending on the subject's metabolism and dosage. Levomethamphetamine metabolizes completely into levoamphetamine after a period of time.<ref name="DeGeorgeWeber2012">{{cite web | vauthors = DeGeorge M, Weber J | date = 30 November 2012 |title = Methamphetamine Urine Toxicology: An In-depth Review|url = http://www.practicalpainmanagement.com/treatments/pharmacological/non-opioids/methamphetamine-urine-toxicology-depth-review |access-date = 2016-02-21|archive-url = https://web.archive.org/web/20160213145044/http://www.practicalpainmanagement.com/treatments/pharmacological/non-opioids/methamphetamine-urine-toxicology-depth-review|archive-date = 13 February 2016|url-status = live | work = Practical Pain Management | publisher = Vertical Health LLC }}</ref>

The mean [[elimination half-life]] of levomethamphetamine ranges between 10.2 and 15.0{{nbsp}}hours.<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /> For comparison, the elimination half-life of [[dextromethamphetamine]] was around 10.2 to 10.7{{nbsp}}hours in the same studies.<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /> The [[clearance (pharmacology)|clearance]] of levomethamphetamine is 15.5 to 19.1{{nbsp}}L/h or 0.221{{nbsp}}L/h⋅kg.<ref name="BarkholtzHadzimaMiles2023" /><ref name="MendelsonUemuraHarris2006" /><ref name="LiLopezGalloway2010" />

With [[selegiline]] at an oral dose of 10{{nbsp}}mg, levomethamphetamine and levoamphetamine are eliminated in urine and recovery of levomethamphetamine is 20 to 60% (or about 2–6{{nbsp}}mg) while that of levoamphetamine is 9 to 30% (or about 1–3{{nbsp}}mg).<ref name="HeinonenLammintausta1991">{{cite journal |vauthors=Heinonen EH, Lammintausta R |date=1991 |title=A review of the pharmacology of selegiline |journal=Acta Neurol Scand Suppl |volume=136 |issue= |pages=44–59 |doi=10.1111/j.1600-0404.1991.tb05020.x |pmid=1686954}}</ref>

==Chemistry==
Levomethamphetamine, also known as <small>L</small>-α,''N''-dimethyl-β-phenylethylamine or as <small>L</small>-''N''-methylamphetamine, is a [[substituted phenethylamine]] and [[substituted amphetamine|amphetamine]].<ref name="BarkholtzHadzimaMiles2023" /><ref name="PubChem">{{cite web | title=Levmetamfetamine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/36604 | access-date=31 July 2024}}</ref> It is the [[levorotatory]] [[enantiomer]] of [[methamphetamine]].<ref name="BarkholtzHadzimaMiles2023" /> [[Racemic mixture|Racemic]] methamphetamine contains two [[optical isomer]]s in equal amounts, dextromethamphetamine (the dextrorotatory enantiomer) and levomethamphetamine.<ref name="BarkholtzHadzimaMiles2023" />

==History==
[[Methamphetamine]], a [[racemic mixture]] of [[dextromethamphetamine]] and levomethamphetamine, was first discovered and [[chemical synthesis|synthesized]] in 1919.<ref name="VearrierGreenbergMiller2012">{{cite journal | vauthors = Vearrier D, Greenberg MI, Miller SN, Okaneku JT, Haggerty DA | title = Methamphetamine: history, pathophysiology, adverse health effects, current trends, and hazards associated with the clandestine manufacture of methamphetamine | journal = Disease-a-Month | volume = 58 | issue = 2 | pages = 38–89 | date = February 2012 | pmid = 22251899 | doi = 10.1016/j.disamonth.2011.09.004 | quote = Japanese chemist Akira Ogata first synthesized methamphetamine in 1919 using ephedrine as a precursor. [...] In 1959 the S. Pfeiffer Company began producing Valo inhalers that contained 150-200 mg of methamphetamine.4,5 [...] Temmler Pharmaceutical Company introduced Pervitin in 1938 to the European market. Pervitin was available as 3 mg tablets that physicians could provide for the German military units. }}</ref><ref name="Ciccarone2011">{{cite journal | vauthors = Ciccarone D | title = Stimulant abuse: pharmacology, cocaine, methamphetamine, treatment, attempts at pharmacotherapy | journal = Prim Care | volume = 38 | issue = 1 | pages = 41–58 | date = March 2011 | pmid = 21356420 | pmc = 3056348 | doi = 10.1016/j.pop.2010.11.004 | url = | quote = In 1919, Japanese chemist Akira Ogata, as part of his effort to prove the structure of ephedrine, reported the synthesis of the closely related compound we now call methamphetamine, and this result was described in the Western literature (Amatsu & Kubota, 1913; Lee, 2011; Ogata, 1920). [...] As a result, when competitors began to consider emulating SKF's success in the late 1930s, they turned to methamphetamine, which had nearly indistinguishable effects but—because its synthesis together with its pharmacological characteristics was published before 1920—was free from patent encumbrance. [...] In any event, by 1940 Benzedrine Sulfate had achieved medical acclaim and quickly growing sales as an antidepressant effective for milder forms of the condition, both in the United States and the United Kingdom. In Germany, the Temmler drug firm quickly copied SKF, marketing methamphetamine (again, unprotected by patents) tablets under the Pervitin brand, with claims that it restored "joy in work" in cases of mild depression around 1938 (Rasmussen, 2006; Steinkamp, 2006).}}</ref> Methamphetamine was first introduced for medical use in 1938 in oral form under the brand name Pervitin in [[Germany]].<ref name="VearrierGreenbergMiller2012" /><ref name="Ciccarone2011" /> [[Over-the-counter drug|Over-the-counter]] [[nasal decongestant]] [[inhaler]]s containing [[enantiopure]] levomethamphetamine, originally labeled with the chemical name ''l-desoxyephedrine'', were first introduced in 1958 under the brand name Vicks Inhaler.<ref name="WessonSmithMorgan1986">{{cite journal |vauthors=Wesson DR, Smith DE, Morgan JP |date=1986 |title=The international scheduling of OTC inhaler ingredients: an abuse perspective |journal=J Psychoactive Drugs |volume=18 |issue=2 |pages=151–4 |doi= 10.1080/02791072.1986.10471394|doi-broken-date=11 November 2024 |pmid=2874202 |quote=The Vicks® Inhaler initially contained only aromatics, but in 1958. Vicks added l-methamphetamine. The package labeling used the alternative chemical term, l-desoxyephedrine. Thus, prior to 1958, it contained nothing psychoactive and had no association with drug abuse.}}</ref><ref name="DiCyanHessman1972">{{cite book | vauthors = Di Cyan E, Hessman L | title=Without Prescription: A Guide to the Selection and Use of Medicines You Can Get Over-the-counter Without Prescription, for Safe Self-medication | publisher=Simon and Schuster | series=A Fireside book | year=1972 | isbn=978-0-671-21137-0 | url=https://books.google.com/books?id=eHdrAAAAMAAJ | access-date=9 July 2024 | page=53 | quote = Vicks Inhaler (Vick)—Contains l-desoxyephedrine, [menthol], camphor, methyl salicylate, and bromyl acetate.}}</ref><ref name="KrantzCarrAviado1972">{{cite book | vauthors = Krantz JC, Carr CJ, Aviado DM | title=Krantz and Carr's Pharmacologic Principles of Medical Practice: A Textbook on Pharmacology and Therapeutics for Students and Practitioners of Medicine, Pharmacy, and Dentistry | publisher=Williams & Wilkins | issue=v. 10 | year=1972 | isbn=978-0-683-00292-8 | url=https://books.google.com/books?id=C-tsAAAAMAAJ | access-date=9 July 2024 | page=389 | quote = Methamphetamine, also known as desoxyephedrine, is available as an inhalant (VICKS INHALER). The volatile base of methamphetamine is mixed with menthol, camphor, methyl salicylate, oil of sassafras and bornylacetate, which add to the customer acceptability of the inhalant. The nasal decongestant effect of methamphetamine has been demonstrated in the experimental animal (Aviado et al., 1959). The other pharmacologic features of methamphetamine are discussed under its use as a vasopressor drug (Section VIII) and an anorexigenic drug (Section XV).}}</ref> By 1995, the brand name was changed to Vicks Vapor Inhaler.<ref name="AmericanPharmaceuticalAssociation1995">{{cite book | author=American Pharmaceutical Association | title=Handbook of Non-prescription Drugs | publisher=American Pharmaceutical Association | year=1995 | isbn=978-0-917330-70-4 | url=https://books.google.com/books?id=MMshAQAAMAAJ | access-date=9 July 2024 | page=109 | quote = Product & Manufacturer or Supplier: Vicks Vapor Inhaler, Procter & Gamble. Dosage Form: nasal inhaler. Sympathomimetic Agent: levodesoxyephedrine, 50 mg/inhaler. Preservative: None. Other Ingredients: bornyl acetate • camphor • lavender oil • menthol.}}</ref><ref name="Rapp1997">{{cite book | vauthors = Rapp R | title=The Pill Book Guide | publisher=Bantam Books | year=1997 | isbn=978-0-553-57729-7 | url=https://books.google.com/books?id=0M-nLE9MYO4C | access-date=9 July 2024 | page=220 | quote = Vicks Vapor Inhaler (VIKS): Generic Ingredient:  l-Desoxyephedrine. Type of Drug: Topical decongestant. Used for: Temporary relief of nasal congestion due to colds and allergies. General Information: Vicks Vapor Inhaler contains l-desoxyephedrine, which acts as a topical decongestant by narrowing or constricting blood vessels in the nose. This action reduces the blood supplied to the nose and decreases the swelling of nasal mucous membranes. [...]}}</ref> In 1998, the [[United States]] [[Food and Drug Administration]] (FDA) required that the chemical name on the labeling be changed from ''l''-desoxyephedrine to ''levmetamfetamine''.<ref name="Bovett2006">{{cite journal | vauthors = Bovett R | title = Meth Epidemic Solutions | journal = North Dakota Law Review | date = January 2006 | volume = 82 | issue = 4 | pages = 1195–1216 | url = https://commons.und.edu/ndlr/vol82/iss4/5 | quote = Rules & Regulations Dep't of Health & Human Services, 61 Fed. Reg. 9,570 (Mar. 8, 1996) (codified at 21 C.F.R pt. 321). Vicks® Vapor Inhaler uses this active ingredient. For a time, the active ingredient was labeled "l-desoxyephedrine," which is simply another name for lmeth. Id. The FDA later changed the labeling requirement to "levmetamfetamine." Rules & Regulations Dep't of Health & Human Services, 63 Fed. Reg. 40,647 (July 30, 1998) (codified at 21 C.F.R. pts. 310 and 321).}}</ref>

==Society and culture==
===Legal status===
Levomethamphetamine is a [[controlled substance]] in the [[Philippines]].<ref name="DDB2023">{{cite web | title=Updated Lists of Scheduled Controlled Substances as of 18 April 2023 | website=ddb.gov.ph | publisher=Republic of the Philippines, Office of the President, Dangerous Drug Board | date = 18 April 2023 | url=https://ddb.gov.ph/wp-content/uploads/2023/05/Updated-Lists-of-controlled-substances-as-of-April-2023-1-AutoRecovered.pdf | access-date=17 January 2025 }}</ref>

===Recreational use===
As of 2006, there were no studies demonstrating "drug liking" scores of oral levomethamphetamine that are similar to [[racemic mixture|racemic]] methamphetamine or dextromethamphetamine in either [[recreational drug use|recreational]] users or [[medication|medicinal]] users.<ref name="MendelsonUemuraHarris2006" /> In any case, [[drug abuse|misuse]] of levomethamphetamine at high doses has been reported.<ref name="MendelsonMcGlothlinHarris2008">{{cite journal | vauthors = Mendelson JE, McGlothlin D, Harris DS, Foster E, Everhart T, Jacob P, Jones RT | title = The clinical pharmacology of intranasal l-methamphetamine | journal = BMC Clin Pharmacol | volume = 8 | issue = | pages = 4 | date = July 2008 | pmid = 18644153 | pmc = 2496900 | doi = 10.1186/1472-6904-8-4 | doi-access = free | url = | quote = The 64-inhalation condition produced a small (change score of ~6) increase in "Good Drug Effect" suggesting a low potential for abuse even though occurrences of inhaler abuse is reported in the literature [1,18,19]. Larger doses of intravenous lmethamphetamine are psychoactive and may have some abuse potential in methamphetamine users [16].}}</ref><ref name="Gal1982">{{cite journal | vauthors = Gal J | title=Amphetamines in Nasal Inhalers | journal=Journal of Toxicology: Clinical Toxicology | volume=19 | issue=5 | date=1982 | issn=0731-3810 | doi=10.3109/15563658208992508 | pages=517–518}}</ref><ref name="HalleKesslerAlvarez1985">{{cite journal | vauthors = Halle AB, Kessler R, Alvarez M | title = Drug abuse with Vicks nasal inhaler | journal = South Med J | volume = 78 | issue = 6 | pages = 761–2 | date = June 1985 | pmid = 4002016 | doi = 10.1097/00007611-198506000-00043 | url = }}</ref><ref name="FerrandoMcCorveySimon1988">{{cite journal | vauthors = Ferrando RL, McCorvey E, Simon WA, Stewart DM | title = Bizarre behavior following the ingestion of levo-desoxyephedrine | journal = Drug Intell Clin Pharm | volume = 22 | issue = 3 | pages = 214–217 | date = March 1988 | pmid = 3366062 | doi = 10.1177/106002808802200308 | url = }}</ref>

In 2012, tighter controls in [[Mexico]] on certain methamphetamine [[precursor (chemistry)|precursor]]s like [[ephedrine]] and [[pseudoephedrine]] led to a greater percentage of [[illicit drug|illicit]] methamphetamine from Mexican [[drug cartel]]s consisting of a higher ratio of levomethamphetamine to dextromethamphetamine within batches of racemic methamphetamine.<ref name="CunninghamMaxwellCampollo2013">{{cite journal | vauthors = Cunningham JK, Maxwell JC, Campollo O, Liu LM, Lattyak WJ, Callaghan RC | title = Mexico's precursor chemical controls: emergence of less potent types of methamphetamine in the United States | journal = Drug Alcohol Depend | volume = 129 | issue = 1–2 | pages = 125–36 | date = April 2013 | pmid = 23127541 | doi = 10.1016/j.drugalcdep.2012.10.001 | url = }}</ref>

==Manufacturing==
The manufacturing of levomethamphetamine products for therapeutic use is done according to government regulations and pharmacopeia monographs. The most recent change in [[Food and Drug Administration]] regulations for levomethamphetamine inhalers was in 1994, with the adoption of a final monograph.<ref>{{Cite journal |last=Research |first=Center for Drug Evaluation and |date=2022-02-28 |title=Rulemaking History for OTC Nasal Decongestant Drug Products |url=https://www.fda.gov/drugs/historical-status-otc-rulemakings/rulemaking-history-otc-nasal-decongestant-drug-products |archive-url=https://web.archive.org/web/20220626171421/https://www.fda.gov/drugs/historical-status-otc-rulemakings/rulemaking-history-otc-nasal-decongestant-drug-products |url-status=dead |archive-date=26 June 2022 |journal=FDA |language=en}}</ref>

==Notes==
{{notelist}}

==References==
{{Reflist}}

{{Methamphetamine}}
{{Decongestants}}
{{Stimulants}}
{{Monoamine releasing agents}}
{{Phenethylamines}}

[[Category:Enantiopure drugs]]
[[Category:Methamphetamine]]
[[Category:Methamphetamines]]
[[Category:Norepinephrine-dopamine releasing agents]]
[[Category:Selegiline]]
[[Category:Substituted amphetamines]]
[[Category:Sympathomimetics]]
[[Category:TAAR1 agonists]]
[[Category:VMAT inhibitors]]