Levomethamphetamine

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Levomethamphetamine
INN: Levmetamfetamine
Clinical data
Trade namesVicks Inhaler; Vicks Vapor Inhaler; Pervitin
Other namesLevmetamfetamine; L-Methamphetamine; R-(-)-Methamphetamine; Levodesoxyephedrine; L-Desoxyephedrine
Routes of
administration		Medical: Inhalation (nasal)
Recreational: Oral, intravenous, insufflation, inhalation, suppository
Legal status
Legal status
Pharmacokinetic data
BioavailabilityOral: ~100%[2][3]
MetabolismLiver (CYP2D6)[5][6]
MetabolitesLevoamphetamine[2][4][3]
Elimination half-life10–15 hours[2][4][3]
ExcretionUrine (41–49% unchanged, 2–3% as levoamphetamine)[2][4][3]
Identifiers
  • (R)-N-methyl-1-phenylpropan-2-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard100.046.974 Edit this at Wikidata
Chemical and physical data
FormulaC10H15N
Molar mass149.237 g·mol−1
3D model (JSmol)
ChiralityLevorotatory enantiomer
  • 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)

Levomethamphetamine, also known as l-desoxyephedrine[note 1] and sold under the brand name Vicks Vapor Inhaler among others, is a sympathomimetic, decongestant, and stimulant medication which is used to treat nasal congestion.[2] It is available over-the-counter at low doses as a decongestant in the United States and is taken by inhalation for this use.[2]

Levomethamphetamine act as a selective releasing agent of norepinephrine.[7][8][4] It also induces the release of dopamine to a far lesser extent.[7][9][4] Levomethamphetamine is an amphetamine and is the levorotatory enantiomer of the better-known methamphetamine.[2] The effects of levomethamphetamine are distinct from those of racemic methamphetamine and dextromethamphetamine and it does not have the same misuse potential as these substances.[2][10][11][4][12]

Methamphetamine was first discovered in 1919[13][14] and was introduced for medical use in oral form in 1938 under the brand name Pervitin.[15] Decongestant inhalers containing enantiopure levomethamphetamine were introduced in 1958 under the brand name Vicks Inhaler.[15] In addition to being used in pharmaceutical drugs itself, levomethamphetamine is a known active metabolite of certain other drugs, such as selegiline (L-deprenyl).[5][16]

Medical uses

Nasal decongestion

Levomethamphetamine is used as a nasal decongestant.[2]

Available forms

Levomethamphetamine is available in the form of decongestant inhalers containing 50 mg total levomethamphetamine per inhaler and delivering between 0.04 and 0.15 mg of the drug per inhalation.[2] Inhalers with a total of 113 mg levomethamphetamine were previously marketed in the United States, but the total amount was eventually reduced to 50 mg.[2] These inhalers have been sold under brand names like Vicks Inhaler and Vicks Vapor Inhaler.[15][2]

Levomethamphetamine was previously available in the form of racemic methamphetamine, a 1:1 combination of dextromethamphetamine and levomethamphetamine, in the form of oral tablets under brand names like Pervitin.[13][14] However, these formulations were eventually discontinued.[2][13][14] Dextromethamphetamine is still marketed under the brand name Desoxyn, but this medication is enantiopure and does not contain any levomethamphetamine.[17]

Side effects

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

Pharmacology

Pharmacodynamics

Levomethamphetamine acts as a selective norepinephrine releasing agent.[8][7][9][4] The potencies of levomethamphetamine, levoamphetamine, dextromethamphetamine, and dextroamphetamine in terms of norepinephrine release in vitro and in vivo in rats are all similar.[18][19][20][12][7]

Conversely, whereas dextromethamphetamine and dextroamphetamine are relatively balanced releasers of dopamine and norepinephrine in vitro, levomethamphetamine is about 15- to 20-fold less potent in inducing dopamine release relative to norepinephrine release.[7][9][4][8][20] 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.[19][18][12]

Monoamine release of levomethamphetamine and related substances (EC50Tooltip Half maximal effective concentration, nM)[7][21]
Compound 5-HTTooltip Serotonin NETooltip Norepinephrine DATooltip Dopamine Type Class Ref
Amphetamine ND ND ND NDRA Amphetamine ND
  D-Amphetamine 698–1765 6.6–7.2 5.8–24.8 NDRA Amphetamine [8][22]
  L-Amphetamine ND ND ND NRA Amphetamine ND
Ephedrine ND ND ND NDRA Cathinol ND
  D-Ephedrine >10000 43.1–72.4 236–1350 NDRA Cathinol [8]
  L-Ephedrine >10000 218 2104 NRA Cathinol [8][23]
Methamphetamine ND ND ND NDRA Amphetamine ND
  D-Methamphetamine 736–1291.7 12.3–13.8 8.5–24.5 NDRA Amphetamine [8][24]
  L-Methamphetamine 4640 28.5 416 NRA Amphetamine [8]
Pseudoephedrine ND ND ND NDRA Cathinol ND
  D-Pseudoephedrine >10000 4092 9125 NDRA Cathinol [23]
  L-Pseudoephedrine >10000 224 1988 NRA Cathinol [23]
Note: The smaller the value, the more strongly the substance releases the neurotransmitter.

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.[25][26][10] For comparison, levoamphetamine is only 1- to 4-fold less potent than dextroamphetamine in its stimulating and reinforcing effects in monkeys and humans.[18][27]

The effects of levomethamphetamine are qualitatively distinct relative to those of racemic methamphetamine and dextromethamphetamine and it does not possess the same potential for euphoria or addiction that these drugs possesses.[2][10][11][4][12] In clinical studies, levomethamphetamine at oral doses of 1 to 10 mg has been found not to affect subjective drug responses, heart rate, blood pressure, core temperature, electrocardiography, respiration rate, oxygen saturation, or other clinical parameters.[2][3] As such, doses of levomethamphetamine of less than or equal to 10 mg have no significant physiological or subjective effects.[2][3] However, higher doses of levomethamphetamine, for instance 0.25 to 0.5 mg/kg (mean doses of ~18–37 mg) intravenously, have been reported to produce significant pharmacological effects, including increased heart rate and blood pressure, increased respiration rate, and subjective effects like intoxication and drug liking.[2][4] On the other hand, in contrast to dextromethamphetamine, levomethamphetamine also produces subjective "bad" or aversive drug effects.[9][4] Among the physiological effects of levomethamphetamine is vasoconstriction, which makes it useful for nasal decongestion.[28]

For comparison to levomethamphetamine, 5 to 60 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 and mood.[29][30][31][27][note 2]

In addition to its norepinephrine-releasing activity, levomethamphetamine is also an agonist of the trace amine-associated receptor 1 (TAAR1).[32][33][34]

Pharmacokinetics

Absorption

The bioavailability of levomethamphetamine is approximately 100%.[2][3] The peak levels of levomethamphetamine range from 3.3 to 31.4 ng/mL with single oral doses of 1 to 10 mg and from 65.4 to 125.9 ng/mL with single intravenous doses of 0.25 to 0.5 mg/kg.[2][4][35] The area-under-the-curve (AUC) levels of levomethamphetamine range from 73.0 to 694.7 ng⋅h/mL with single oral doses of 1 to 10 mg and from 1,190.7 to 2,368.1 mg/kg with single intravenous doses of 0.25 to 0.5 mg/kg.[2][4][35]

Distribution

The volume of distribution of levomethamphetamine is 288.5 to 315.5 L or 4.15 to 4.17 L/kg.[2][4][3]

Metabolism

The pharmacokinetics of levomethamphetamine generated as a metabolite from selegiline have been found to be significantly different in CYP2D6 poor metabolizers versus extensive metabolizers.[5][6] 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.[5][6] These findings suggest that CYP2D6 may be significantly involved in the metabolism of levomethamphetamine.[5][6]

Levomethamphetamine is metabolized into levoamphetamine in small amounts.[2][4][3]

Elimination

Levomethamphetamine is excreted in urine 40.8 to 49.0% as unchanged levomethamphetamine and 2.1 to 3.3% as levoamphetamine.[2][4][3]

The mean elimination half-life of levomethamphetamine ranges between 10.2 and 15.0 hours.[2][4] For comparison, the elimination half-life of dextromethamphetamine was around 10.2 to 10.7 hours in the same studies.[2][4] The clearance of levomethamphetamine is 15.5 to 19.1 L/h or 0.221 L/h⋅kg.[2][4][3]

With selegiline at a oral dose of 10 mg, levomethamphetamine and levoamphetamine are eliminated in urine and recovery of levomethamphetamine is 20 to 60% (or about 2–6 mg) while that of levoamphetamine is 9 to 30% (or about 1–3 mg).[16]

Chemistry

Detection in body fluids

Levomethamphetamine can register on urine drug tests as either methamphetamine, amphetamine, or both, depending on the subject's metabolism and dosage. Levomethamphetamine metabolizes completely into levoamphetamine after a period of time.[36]

History

Methamphetamine, a racemic mixture of dextromethamphetamine and levomethamphetamine, was first discovered and synthesized in 1919.[13][14] Methamphetamine was first introduced for medical use in 1938 in oral form under the brand name Pervitin in Germany.[13][14] Over-the-counter nasal decongestant inhalers containing enantiopure levomethamphetamine, originally labeled with the chemical name l-desoxyephedrine, were first introduced in 1958 under the brand name Vicks Inhaler.[15][37][38] By 1995, the brand name was changed to Vicks Vapor Inhaler.[39][40] 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.[41]

Society and culture

Recreational use

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.[4] In any case, misuse of levomethamphetamine at high doses has been reported.[42][43][44][45]

In recent years, tighter controls in Mexico on certain methamphetamine precursors like ephedrine and pseudoephedrine has led to a greater percentage of illicit methamphetamine from Mexican drug cartels consisting of a higher ratio of levomethamphetamine to dextromethamphetamine within batches of racemic methamphetamine.[46] However, in recent years, cartels have used chiral separation to produce relatively pure dextromethamphetamine from the racemic substance.

Other drugs

Selegiline

Main article: Selegiline

Levomethamphetamine is a major active metabolite of selegiline (L-deprenyl; N-propargyl-L-methamphetamine).[16][47] Selegiline is a monoamine oxidase inhibitor (MAOI), specifically a selective inhibitor of monoamine oxidase B (MAO-B) at lower doses and a dual inhibitor of both monoamine oxidase A (MAO-A) and MAO-B at higher doses.[16][48] It also has additional activities, such as acting as a catecholaminergic activity enhancer (CAE), possibly via agonism of the TAAR1, and having potential neuroprotective effects.[49][48][50] Selegiline is clinically used as an antiparkinsonian agent in the treatment of Parkinson's disease and as an antidepressant in the treatment of major depressive disorder.[49][48]

In addition to levomethamphetamine, selegiline also metabolizes into levoamphetamine.[47][16] With a 10 mg oral dose of selegiline, about 2 to 6 mg levomethamphetamine and 1 to 3 mg levoamphetamine is excreted in urine.[16][51][47][52] As levomethamphetamine and levoamphetamine are norepinephrine and/or dopamine releasing agents, they may contribute to the effects and side effects of selegiline.[53][54][7] This may particularly include cardiovascular and sympathomimetic effects of selegiline.[53][55][56][57] Other selective MAO-B inhibitors that do not metabolize into amphetamine metabolites or have associated cardiovascular effects, such as rasagiline, have also been developed and introduced.[53][58]

Because selegiline metabolizes into levomethamphetamine and levoamphetamine, people taking selegiline can erroneously test positive for amphetamines on drug tests.[59][60]

Notes

  1. ^ Other names include levmetamfetamine (INNTooltip International Nonproprietary Name), L-methamphetamine, R-(-)-methamphetamine, levodesoxyephedrine, and L-desoxyephedrine.
  2. ^ Smith & Davis (1977) reviewed 11 clinical studies of dextroamphetamine and levoamphetamine including doses and potency ratios in terms of a variety of psychological and behavioral effects.[27] The summaries of these studies are in Table 1 of the paper.[27]

References

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  12. ^ a b c d 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. 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.
  13. ^ a b c d e Vearrier D, Greenberg MI, Miller SN, Okaneku JT, Haggerty DA (February 2012). "Methamphetamine: history, pathophysiology, adverse health effects, current trends, and hazards associated with the clandestine manufacture of methamphetamine". Disease-A-Month. 58 (2): 38–89. doi:10.1016/j.disamonth.2011.09.004. PMID 22251899. 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.
  14. ^ a b c d e Ciccarone D (March 2011). "Stimulant abuse: pharmacology, cocaine, methamphetamine, treatment, attempts at pharmacotherapy". Prim Care. 38 (1): 41–58. doi:10.1016/j.pop.2010.11.004. PMC 3056348. PMID 21356420. 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).
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  24. ^ Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, et al. (2012). "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue". Neuropsychopharmacology. 37 (5): 1192–1203. doi:10.1038/npp.2011.304. PMC 3306880. PMID 22169943.
  25. ^ Nishimura T, Takahata K, Kosugi Y, Tanabe T, Muraoka S (May 2017). "Psychomotor effect differences between l-methamphetamine and d-methamphetamine are independent of murine plasma and brain pharmacokinetics profiles". J Neural Transm (Vienna). 124 (5): 519–523. doi:10.1007/s00702-017-1694-y. PMC 5399046. PMID 28213761. 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.
  26. ^ Siemian JN, Xue Z, Blough BE, Li JX (July 2017). "Comparison of some behavioral effects of d- and l-methamphetamine in adult male rats". Psychopharmacology (Berl). 234 (14): 2167–2176. doi:10.1007/s00213-017-4623-8. PMC 5482751. PMID 28386698.
  27. ^ a b c d Smith RC, Davis JM (June 1977). "Comparative effects of d-amphetamine, l-amphetamine, and methylphenidate on mood in man". Psychopharmacology (Berl). 53 (1): 1–12. doi:10.1007/BF00426687. PMID 407607. [...] 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. [...]
  28. ^ Pray SW (19 February 2010). "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/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.
  29. ^ Silverstone T, Wells B (1980). "Clinical Psychopharmacology of Amphetamine and Related Compounds". Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects. CRC Press. pp. 147–160. doi:10.1201/9780429279843-10. ISBN 978-0-429-27984-3. 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.
  30. ^ Parkes JD, Fenton GW (December 1973). "Levo(-) amphetamine and dextro(+) amphetamine in the treatment of narcolepsy". J Neurol Neurosurg Psychiatry. 36 (6): 1076–81. doi:10.1136/jnnp.36.6.1076. PMC 1083612. PMID 4359162.
  31. ^ Parkes JD, Tarsy D, Marsden CD, Bovill KT, Phipps JA, Rose P, et al. (March 1975). "Amphetamines in the treatment of Parkinson's disease". J Neurol Neurosurg Psychiatry. 38 (3): 232–7. doi:10.1136/jnnp.38.3.232. PMC 491901. PMID 1097600.
  32. ^ "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.
  33. ^ Sotnikova TD, Caron MG, Gainetdinov RR (August 2009). "Trace amine-associated receptors as emerging therapeutic targets". Mol Pharmacol. 76 (2): 229–35. doi:10.1124/mol.109.055970. PMC 2713119. PMID 19389919. 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.
  34. ^ Reese EA, Norimatsu Y, Grandy MS, Suchland KL, Bunzow JR, Grandy DK (January 2014). "Exploring the determinants of trace amine-associated receptor 1's functional selectivity for the stereoisomers of amphetamine and methamphetamine". J Med Chem. 57 (2): 378–390. doi:10.1021/jm401316v. PMID 24354319.
  35. ^ a b Li L, Everhart T, Jacob Iii P, Jones R, Mendelson J (February 2010). "Stereoselectivity in the human metabolism of methamphetamine". Br J Clin Pharmacol. 69 (2): 187–192. doi:10.1111/j.1365-2125.2009.03576.x. PMC 2824480. PMID 20233182.
  36. ^ 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.
  37. ^ Di Cyan E, Hessman L (1972). Without Prescription: A Guide to the Selection and Use of Medicines You Can Get Over-the-counter Without Prescription, for Safe Self-medication. A Fireside book. Simon and Schuster. p. 53. ISBN 978-0-671-21137-0. Retrieved 9 July 2024. Vicks Inhaler (Vick)—Contains l-desoxyephedrine, [menthol], camphor, methyl salicylate, and bromyl acetate.
  38. ^ Krantz JC, Carr CJ, Aviado DM (1972). Krantz and Carr's Pharmacologic Principles of Medical Practice: A Textbook on Pharmacology and Therapeutics for Students and Practitioners of Medicine, Pharmacy, and Dentistry. Krantz and Carr's Pharmacologic Principles of Medical Practice: A Textbook on Pharmacology and Therapeutics for Students and Practitioners of Medicine, Pharmacy, and Dentistry. Williams & Wilkins. p. 389. ISBN 978-0-683-00292-8. Retrieved 9 July 2024. 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 acceptibility 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).
  39. ^ American Pharmaceutical Association (1995). Handbook of Non-prescription Drugs. American Pharmaceutical Association. p. 109. ISBN 978-0-917330-70-4. Retrieved 9 July 2024. 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.
  40. ^ Rapp R (1997). The Pill Book Guide. Bantam Books. p. 220. ISBN 978-0-553-57729-7. Retrieved 9 July 2024. 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. [...]
  41. ^ Bovett R. "Meth Epidemic Solutions". North Dakota Law Review. 82 (4): 5. 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).
  42. ^ Mendelson JE, McGlothlin D, Harris DS, Foster E, Everhart T, Jacob P, et al. (July 2008). "The clinical pharmacology of intranasal l-methamphetamine". BMC Clin Pharmacol. 8: 4. doi:10.1186/1472-6904-8-4. PMC 2496900. PMID 18644153. 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].
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  45. ^ Ferrando RL, McCorvey E, Simon WA, Stewart DM (March 1988). "Bizarre behavior following the ingestion of levo-desoxyephedrine". Drug Intell Clin Pharm. 22 (3): 214–217. doi:10.1177/106002808802200308. PMID 3366062.
  46. ^ Cunningham JK, Maxwell JC, Campollo O, Liu LM, Lattyak WJ, Callaghan RC (April 2013). "Mexico's precursor chemical controls: emergence of less potent types of methamphetamine in the United States". Drug Alcohol Depend. 129 (1–2): 125–36. doi:10.1016/j.drugalcdep.2012.10.001. PMID 23127541.
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