Levomethamphetamine

Last updated

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
Metabolism Hepatic
Elimination half-life 13 - 15 hours [2]
Excretion Renal
Identifiers
  • (R)-N-methyl-1-phenyl-propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard 100.046.974 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C10H15N
Molar mass 149.23 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 Yes check.svgY
  • Key:MYWUZJCMWCOHBA-SECBINFHSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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.

Contents

Pharmacology

Pharmacodynamics

Levomethamphetamine crosses the blood-brain-barrier and acts as a norepinephrine transporter inhibitor [3] and TAAR1 agonist, [4] 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. [3] [5] It does not possess the same potential for euphoria or addiction that dextromethamphetamine possesses. [3] [5] [6] [7] Among its physiological effects are the vasoconstriction that makes it useful for nasal decongestion. [8]

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. [2]

Selegiline

Levomethamphetamine is an active metabolite of the antiparkinson's drug selegiline. [9] Selegiline, a selective monoamine oxidase B (MAOB) inhibitor at low doses, [note 2] is also metabolized into levomethamphetamine and levoamphetamine. [10] [11] This has caused users to test positive for amphetamines. [12] [13]

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. [14] [15]

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. [6]

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. [16] [17]

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. [18]

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.

Related Research Articles

<span class="mw-page-title-main">Stimulant</span> Overarching term covers many drugs that increase activity of the central nervous system

Stimulants is an overarching term that covers many drugs including those that increase the activity of the central nervous system and the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Stimulants are widely used throughout the world as prescription medicines as well as without a prescription as performance-enhancing or recreational drugs. Among narcotics, stimulants produce a noticeable crash or comedown at the end of their effects. The most frequently prescribed stimulants as of 2013 were lisdexamfetamine (Vyvanse), methylphenidate (Ritalin), and amphetamine (Adderall). It was estimated in 2015 that the percentage of the world population that had used cocaine during a year was 0.4%. For the category "amphetamines and prescription stimulants" the value was 0.7%, and for MDMA 0.4%.

<span class="mw-page-title-main">Benzphetamine</span> Chemical compound

Benzphetamine is a substituted amphetamine used short-term along with a doctor-approved, reduced-calorie diet, exercise, and behavioral program for weight loss. It is prescribed for obesity to people who have been unable to lose weight through exercise and dieting alone. It is a prodrug to dextroamphetamine and dextromethamphetamine.

<span class="mw-page-title-main">Methcathinone</span> Psychoactive stimulant

Methcathinone is a monoamine alkaloid and psychoactive stimulant, a substituted cathinone. It is used as a recreational drug due to its potent stimulant and euphoric effects and is considered to be addictive, with both physical and psychological withdrawal occurring if its use is discontinued after prolonged or high-dosage administration. It is usually snorted, but can be smoked, injected, or taken orally.

<span class="mw-page-title-main">Phenethylamine</span> Organic compound, a stimulant in humans

Phenethylamine (PEA) is an organic compound, natural monoamine alkaloid, and trace amine, which acts as a central nervous system stimulant in humans. In the brain, phenethylamine regulates monoamine neurotransmission by binding to trace amine-associated receptor 1 (TAAR1) and inhibiting vesicular monoamine transporter 2 (VMAT2) in monoamine neurons. To a lesser extent, it also acts as a neurotransmitter in the human central nervous system. In mammals, phenethylamine is produced from the amino acid L-phenylalanine by the enzyme aromatic L-amino acid decarboxylase via enzymatic decarboxylation. In addition to its presence in mammals, phenethylamine is found in many other organisms and foods, such as chocolate, especially after microbial fermentation.

<span class="mw-page-title-main">Tranylcypromine</span> Irreversible non-selective MAO inhibitor Antidepressant drug

Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively.

<span class="mw-page-title-main">Phenylpropanolamine</span> Sympathomimetic agent

Phenylpropanolamine (PPA) is a sympathomimetic agent which is used as a decongestant and appetite suppressant. It was commonly used in prescription and over-the-counter cough and cold preparations. In veterinary medicine, it is used to control urinary incontinence in dogs.

<span class="mw-page-title-main">Selegiline</span> Monoamine oxidase inhibitor

Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or tablet taken by mouth or orally disintegrating tablets taken on the tongue for Parkinson's disease and as a patch applied to skin for depression.

α-Methyl-<i>p</i>-tyrosine Chemical compound

α-Methyl-p-tyrosine (AMPT), or simply α-methyltyrosine, also known as racemetirosine, is a tyrosine hydroxylase enzyme inhibitor and is therefore a drug involved in inhibiting the catecholamine biosynthetic pathway. AMPT inhibits tyrosine hydroxylase whose enzymatic activity is normally regulated through the phosphorylation of different serine residues in regulatory domain sites. Catecholamine biosynthesis starts with dietary tyrosine, which is hydroxylated by tyrosine hydroxylase and it is hypothesized that AMPT competes with tyrosine at the tyrosine-binding site, causing inhibition of tyrosine hydroxylase.

<span class="mw-page-title-main">4-Methylaminorex</span> Group of stereoisomers

4-Methylaminorex is a stimulant drug of the 2-amino-5-aryloxazoline class that was first synthesized in 1960 by McNeil Laboratories. It is also known by its street name "U4Euh" ("Euphoria"). It is banned in many countries as a stimulant.

<span class="mw-page-title-main">4-Hydroxyamphetamine</span> Group of stereoisomers

4-Hydroxyamphetamine (4HA), also known as hydroxyamfetamine, hydroxyamphetamine, oxamphetamine, norpholedrine, para-hydroxyamphetamine, and α-methyltyramine, is a drug that stimulates the sympathetic nervous system.

<span class="mw-page-title-main">Rasagiline</span> Chemical compound

Rasagiline is an irreversible inhibitor of monoamine oxidase-B used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases.

<span class="mw-page-title-main">Cyclopentamine</span> Decongestant and stimulant drug

Cyclopentamine is a sympathomimetic alkylamine, classified as a vasoconstrictor. Cyclopentamine was indicated in the past as an over-the-counter (OTC) medication for use as a nasal decongestant, notably in Europe and Australia, but has now been largely discontinued.

<span class="mw-page-title-main">Methamphetamine</span> Central nervous system stimulant

Methamphetamine is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamphetamine was discovered in 1893 and exists as two enantiomers: levo-methamphetamine and dextro-methamphetamine. Methamphetamine properly refers to a specific chemical substance, the racemic free base, which is an equal mixture of levomethamphetamine and dextromethamphetamine in their pure amine forms, but the hydrochloride salt, commonly called crystal meth, is widely used. Methamphetamine is rarely prescribed over concerns involving human neurotoxicity and potential for recreational use as an aphrodisiac and euphoriant, among other concerns, as well as the availability of safer substitute drugs with comparable treatment efficacy such as Adderall and Vyvanse. Dextromethamphetamine is a stronger CNS stimulant than levomethamphetamine.

<span class="mw-page-title-main">Benzofuranylpropylaminopentane</span> Chemical compound

Benzofuranylpropylaminopentane is a drug with an unusual monoamine-release potentiating mechanism of action. It can loosely be grouped with the stimulant or antidepressant drug families, but its mechanism of action is quite different.

<span class="mw-page-title-main">Monoamine releasing agent</span> Class of compounds

A monoamine releasing agent (MRA), or simply monoamine releaser, is a drug that induces the release of a monoamine neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs induce their effects in the body and/or brain via the release of monoamine neurotransmitters, e.g., trace amines, many substituted amphetamines, and related compounds.

<span class="mw-page-title-main">Norepinephrine releasing agent</span> Catecholaminergic type of drug

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

<span class="mw-page-title-main">Substituted phenethylamine</span> Chemical class of organic compounds

Substituted phenethylamines are a chemical class of organic compounds that are based upon the phenethylamine structure; the class is composed of all the derivative compounds of phenethylamine which can be formed by replacing, or substituting, one or more hydrogen atoms in the phenethylamine core structure with substituents.

Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with substituents. The compounds in this class span a variety of pharmacological subclasses, including stimulants, empathogens, and hallucinogens, among others. Examples of substituted amphetamines are amphetamine (itself), methamphetamine, ephedrine, cathinone, phentermine, mephentermine, tranylcypromine, bupropion, methoxyphenamine, selegiline, amfepramone (diethylpropion), pyrovalerone, MDMA (ecstasy), and DOM (STP).

<small>D</small>-Deprenyl Chemical compound

d-Deprenyl, also known as or dextro-N-propargyl-N-methylamphetamine, is an MAO-B inhibitor that metabolizes into d-amphetamine and d-methamphetamine and is therefore also a norepinephrine–dopamine releasing agent. It is the opposite enantiomer of l-deprenyl (selegiline).

References

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    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.
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