LEVMETAMFETAMINE

US Approved OTC

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H15N
Molecular Weight	149.2328
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN[C@H](C)CC1=CC=CC=C1

InChI

InChIKey=MYWUZJCMWCOHBA-SECBINFHSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/otc/130320/vapor-inhaler.html
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22037049 | https://www.drugs.com/uk/vicks-inhaler-leaflet.html | https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=38849 | https://www.ncbi.nlm.nih.gov/pubmed/17015058

Levomethamphetamine is the levorotary (L-enantiomer) form of methamphetamine. Levomethamphetamine is a sympathomimetic vasoconstrictor which is the active ingredient in some over-the-counter (OTC) nasal decongestant inhalers in the United States. Levomethamphetamine crosses the blood-brain-barrier and acts as a TAAR1 agonist, functioning as a selective norepinephrine releasing agent (with few or no effects on the release of dopamine), so it affects the central nervous system, although its effects are qualitatively distinct relative to those of dextromethamphetamine. Levomethamphetamine does not possess the potential for euphoria or addiction that dextromethamphetamine possesses. Among its physiological effects are the vasoconstriction that makes it useful for nasal decongestion. The elimination half-life of levomethamphetamine is between 13.3 and 15 hours, whereas dextromethamphetamine has a half-life of about 10.5 hours. When the nasal decongestant is taken in excess, levomethamphetamine has potential side effects resembling those of other sympathomimetic drugs; these effects include hypertension (elevated blood pressure), tachycardia (rapid heart rate), nausea, stomach cramps, dizziness, headache, sweating, muscle tension, and tremors. Central side effects may include anxiety, insomnia, and anorexia

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Trace amine-associated receptor 1 48 Target ID: CHEMBL5857 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037049	Agonist 2752		3300.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Common cold 58 Sources: https://www.drugs.com/otc/130320/vapor-inhaler.html	Primary	Approved 8583	LEVMETAMFETAMINE Approved Use Unknown
Allergic rhinitis 104 Sources: https://www.drugs.com/otc/130320/vapor-inhaler.html	Primary	Approved 8583	LEVMETAMFETAMINE Approved Use Unknown
Upper respiratory allergies 9 Sources: https://www.drugs.com/otc/130320/vapor-inhaler.html	Primary	Approved 8583	LEVMETAMFETAMINE Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
65.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17015058/	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		LEVMETAMFETAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1190.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17015058/	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		LEVMETAMFETAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17015058/	0.25 mg/kg single, intravenous dose: 0.25 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		LEVMETAMFETAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20233182/	yes

PubMed

Title	Date	PubMed
The effect of low oral doses of (-)-deprenyl and its metabolites on DSP-4 toxicity.	2001	11768624
Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TVP 1012) with selegiline.	2001	11716151
Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates.	2001 Aug	11505218
Lobeline inhibits the neurochemical and behavioral effects of amphetamine.	2001 Mar	11181937
Discrimination in resolving systems. VI. Comparison of the diastereomers of deoxyephedrinium and ephedrinium 4'-fluoromandelates.	2001 May 15	11317345
CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson's disease, as revealed from experiments with recombinant enzymes.	2001 Nov	11602525
Effects of the hallucinogen psilocybin on covert orienting of visual attention in humans.	2002	12097810
Preparation of immunoaffinity columns for direct enantiomeric separation of amphetamine and/or methamphetamine.	2002 Aug 23	12685566
Phosphodiesterase 1B knock-out mice exhibit exaggerated locomotor hyperactivity and DARPP-32 phosphorylation in response to dopamine agonists and display impaired spatial learning.	2002 Jun 15	12077213
Neurochemical and behavioral differences between d-methamphetamine and d-amphetamine in rats.	2003 Feb	12491026
PF 9601N [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine], a new MAO-B inhibitor, attenuates MPTP-induced depletion of striatal dopamine levels in C57/BL6 mice.	2003 Feb	12427476
Screening for and validated quantification of amphetamines and of amphetamine- and piperazine-derived designer drugs in human blood plasma by gas chromatography/mass spectrometry.	2003 Jun	12827635
Chiral analysis of amphetamine-type stimulants using reversed-polarity capillary electrophoresis/positive ion electrospray ionization tandem mass spectrometry.	2003 Jun	12783454
Developmental D-methamphetamine treatment selectively induces spatial navigation impairments in reference memory in the Morris water maze while sparing working memory.	2003 Jun 1	12645039
Elevated environmental temperature and methamphetamine neurotoxicity.	2003 May	12706754
Periadolescent rats (P41-50) exhibit increased susceptibility to D-methamphetamine-induced long-term spatial and sequential learning deficits compared to juvenile (P21-30 or P31-40) or adult rats (P51-60).	2005 Jan-Feb	15681126
Effects of isradipine on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition.	2005 Mar	15452681
NMR regulatory analysis: enantiomeric purity determination for (R)-(-)-desoxyephedrine and antipode methamphetamine.	2006 Mar	16599257
Epoxidation of the methamphetamine pyrolysis product, trans-phenylpropene, to trans-phenylpropylene oxide by CYP enzymes and stereoselective glutathione adduct formation.	2006 Mar 1	16038959
Behavioral effects of ketamine and toxic interactions with psychostimulants.	2006 Mar 16	16542420
Long-term effects of a single adult methamphetamine challenge: minor impact on dopamine fibre density in limbic brain areas of gerbils.	2006 Mar 28	16569246
Chiral separation and quantification of R/S-amphetamine, R/S-methamphetamine, R/S-MDA, R/S-MDMA, and R/S-MDEA in whole blood by GC-EI-MS.	2006 Oct 2	16797258
Comparison of monoamine and corticosterone levels 24 h following (+)methamphetamine, (+/-)3,4-methylenedioxymethamphetamine, cocaine, (+)fenfluramine or (+/-)methylphenidate administration in the neonatal rat.	2006 Sep	16923155
Smokable ("ice", "crystal meth") and non smokable amphetamine-type stimulants: clinical pharmacological and epidemiological issues, with special reference to the UK.	2007	17536161
Perinatal asphyxia reduces dentate granule cells and exacerbates methamphetamine-induced hyperlocomotion in adulthood.	2008	18985150
Redetermination of (+)-methamphetamine hydro-chloride at 90 K.	2008 Apr 30	21202421
Neurochemical consequences of dysphoric state during amphetamine withdrawal in animal models: a review.	2008 Jan	17605106
Rapid nondestructive on-site screening of methylamphetamine seizures by attenuated total reflection fourier transform infrared spectroscopy.	2008 Jun	18559151
Evaluation of effects of methamphetamine repeated dosing on proliferation and apoptosis of rat germ cells.	2008 Mar-Apr	18446649
Identification of impurities and statistical classification of methamphetamine hydrochloride drugs seized in China.	2008 Nov 20	19008060
Local hippocampal methamphetamine-induced reinforcement.	2009	19949457
Changes in glutamate/NMDA receptor subunit 1 expression in rat brain after acute and subacute exposure to methamphetamine.	2009	19478962
An electrochemiluminescent sensor for methamphetamine hydrochloride based on multiwall carbon nanotube/ionic liquid composite electrode.	2009 Jan 1	18760586
Rapid analysis of methamphetamine in hair by micropulverized extraction and microchip-based competitive ELISA.	2009 Jan 30	19108964
"Ice" use and eating disorders: a report of three cases.	2009 Mar	18803173
Enantioselective piezoelectric quartz crystal sensor for d-methamphetamine based on a molecularly imprinted polymer.	2010 Aug	20526767
Addiction and cognition.	2010 Dec	22002448

Patents

Sample Use Guides

In Vivo Use Guide

adults and children 12 years of age and over 2 inhalations in each nostril children 6 to under 12 years of age 1 inhalation in each nostril (with adult supervision). The product delivers in each 800 ml of air 0.04 to 0.150 mg of levmetamfetamine

Route of Administration: Nasal

In Vitro Use Guide

TA receptor activation was assayed in RD-HGA16cells stably expressing Gα16 and the hTAAR1 receptor. These cells were plated in HAM’s F-12 medium with 10% fetal bovine serum, 400 µg/ml hygromycin, and 400 µg/ml geneticin at 30,000 cells/well in 96-well, black, clear-bottom plates and incubated at 37 °C 5% CO2 overnight. Activation of hTAAR1 via Levomethamphetamine ((R)-10) was assessed the next day using the Calcium 3 Assay Kit (Molecular Devices). On the day of assay, the culture medium was removed and the cells washed once in 100 µl HBSS buffer containing 0.78 mg/ml probenicid, followed by the addition of 100 µl HBSS buffer plus probenicid and 100 µl of Calcium 3 dye (one-third the suggested concentration). The cells were incubated with the dye at 37 °C for 1 h. Levomethamphetamine were evaluated using 10 different concentrations run in duplicate. These were added to cells at 5 times the final concentration in HBSS/probenicid containing 1.25% DMSO (0.25% final concentration). The effect of test compound on internal calcium mobilization was determined with a FlexStation set for bottom read with 485-nm excitation and 525-nm emission wavelengths

Name

Type

Language

LEVMETAMFETAMINE CII

Preferred Name

English

LEVMETAMFETAMINE

Official Name

English

LEVOMETHAMPHETAMINE

Common Name

English

LEVMETAMFETAMINE [MART.]

Common Name

English

levmetamfetamine [INN]

Common Name

English

LEVMETAMFETAMINE [USP MONOGRAPH]

Common Name

English

Levmetamfetamine [WHO-DD]

Common Name

English

LEVMETAMFETAMINE [USP IMPURITY]

Common Name

English

L-METHAMPHETAMINE

Common Name

English

(-)-(R)-N,.ALPHA.-DIMETHYLPHENETHYLAMINE

Systematic Name

English

LEVMETAMFETAMINE [USAN]

Common Name

English

BENZENEETHANAMINE, N,.ALPHA.-DIMETHYL-, (R)-

Systematic Name

English

LEVMETAMFETAMINE CII [USP-RS]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29747