METHAMPHETAMINE

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-VIFPVBQESA-N

InChI=1S/C10H15N/c1-9(11-2)8-10-6-4-3-5-7-10/h3-7,9,11H,8H2,1-2H3/t9-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C10H15N
Molecular Weight	149.2328
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9800366 | http://www.legacyhealth.org/for-health-professionals/refer-a-patient/laboratory-services/test-table/dl-methamphetamine-isomers-confirmation-urine.aspxhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2007/005378s026lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/24484975

Methamphetamine is a strong central nervous system (CNS) stimulant and is a sympathomimetic drug. It is approved under the brand name DESOXYN for the treatment of attention deficit disorder with hyperactivity (ADHD) and exogenous obesity. It is a scheduled drug in most countries due to its high potential for addiction and abuse. Methamphetamine enters the brain and triggers a cascading release of norepinephrine, dopamine and serotonin. To a lesser extent methamphetamine acts as a dopaminergic and adrenergic reuptake inhibitor and in high concentrations as a monamine oxidase inhibitor (MAOI). The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown. Methamphetamine has been identified as a potent full agonist of trace amine-associated receptor 1, and also, as an agonist of the alpha-2 adrenergic receptors. Methamphetamine increases extracellular dopamine in reward-relevant pathways by interacting at vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine uptake and promote dopamine release from synaptic vesicles, increasing cytosolic dopamine available for reverse transport by the dopamine transporter (DAT).

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Monoamine transporter 10 Target ID: CHEMBL2363064 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19897077	Negative Allosteric Modulator 42
Synaptic vesicular amine transporter 56 Target ID: Q05940 Gene ID: 6571.0 Gene Symbol: SLC18A2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/24484975	Inhibitor 8228
Trace amine-associated receptor 1 47 Target ID: Q96RJ0 Gene ID: 134864.0 Gene Symbol: TAAR1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17218486	Agonist 2662
Adrenergic receptor alpha-2 113 Target ID: CHEMBL2095158 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12453616	Agonist 2662

Conditions

Condition	Modality	Highest Phase	Product
Attention deficit hyperactivity disorder 68 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/005378s026lbl.pdf	Primary	Approved 8360	DESOXYN Approved Use Attention Deficit Disorder with Hyperactivity: DESOXYN tablets are indicated as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children over 6 years of age with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted. Exogenous Obesity: as a short-term (i.e., a few weeks) adjunct in a regimen of weight reduction based on caloric restriction, for patients in whom obesity is refractory to alternative therapy, e.g., repeated diets, group programs, and other drugs. Launch Date -8.2062718E11
Exogenous obesity 19 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/005378s026lbl.pdf	Palliative	Approved 8360	DESOXYN Approved Use Attention Deficit Disorder with Hyperactivity Methamphetamine hydrochloride tablets are indicated as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children over 6 years of age with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted. Exogenous Obesity As a short-term (i.e., a few weeks) adjunct in a regimen of weight reduction based on caloric restriction, for patients in whom obesity is refractory to alternative therapy, e.g., repeated diets, group programs, and other drugs. The limited usefulness of methamphetamine hydrochloride tablets (see CLINICAL PHARMACOLOGY) should be weighed against possible risks inherent in use of the drug, such as those described below. Launch Date -8.2062718E11
Unknown 2565

C_max

Value	Dose	Co-administered	Analyte	Population
19.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1362938/	0.125 mg/kg single, oral dose: 0.125 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		METHAMPHETAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
330 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1362938/	0.125 mg/kg single, oral dose: 0.125 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		METHAMPHETAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.46 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1362938/	0.125 mg/kg single, oral dose: 0.125 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		METHAMPHETAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 g single, oral (max) Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://pubmed.ncbi.nlm.nih.gov/26402425/	healthy, adult n = 25 Health Status: healthy Condition: methamphetamine dependence Age Group: adult Sex: unknown Population Size: 25 Sources: https://pubmed.ncbi.nlm.nih.gov/26402425/	Disc. AE: Intoxication... AEs leading to discontinuation/dose reduction: Intoxication (25 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/26402425/
40 mg single, oral Dose: 40 mg Route: oral Route: single Dose: 40 mg Sources: https://pubmed.ncbi.nlm.nih.gov/32986459/	healthy, adult n = 19 Health Status: healthy Age Group: adult Sex: unknown Population Size: 19 Sources: https://pubmed.ncbi.nlm.nih.gov/32986459/	Sources: https://pubmed.ncbi.nlm.nih.gov/32986459/

AEs

AE	Significance	Dose	Population
Intoxication	25 patients Disc. AE	2 g single, oral (max) Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: https://pubmed.ncbi.nlm.nih.gov/26402425/	healthy, adult n = 25 Health Status: healthy Condition: methamphetamine dependence Age Group: adult Sex: unknown Population Size: 25 Sources: https://pubmed.ncbi.nlm.nih.gov/26402425/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1193 inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 595 OAT2 144 OAT3 636 OAT4 145 OCT1 506 OCT2 638		GLUT1 9

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/005378s035lbl.pdf#page=	minor
OAT1 599	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/32109742/	no
OAT2 146	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/32109742/	no
OAT3 638	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/32109742/	no
OAT4 145	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/32109742/	no
OCT2 639	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/32109742/	yes [IC50 19.1 uM]
OCT1 523	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/32109742/	yes [IC50 6.5 uM]
GLUT1 15	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/21426580/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/005378s035lbl.pdf#page=	yes

Sourcing

Vendor/Aggregator	ID	URL
ChemIDplus	7563486	https://chem.nlm.nih.gov/chemidplus/id/0007563486
EPA DSSTox	DTXSID20226543	https://comptox.epa.gov/dashboard/DTXSID20226543
PubChem	71586915	https://pubchem.ncbi.nlm.nih.gov/compound/71586915
Wikidata	Q27281863

PubMed

Title	Date	PubMed
Determination of d-methamphetamine in urine after administration of d- or dl-methamphetamine to rats by radioimmunoassay using optically sensitive antiserum.	1982 Jul	7119715
Methamphetamine--properties and analytical methods of enantiomer determination.	1998 Aug 31	9800366
HPLC with fluorescence detection of methamphetamine and amphetamine in segmentally analyzed human hair.	1999 Apr	10605878
Methamphetamine generates peroxynitrite and produces dopaminergic neurotoxicity in mice: protective effects of peroxynitrite decomposition catalyst.	1999 Aug 7	10433983
Methamphetamine administration causes overexpression of nNOS in the mouse striatum.	1999 Dec 18	10642852
The role of gamma-aminobutyric acid (GABA)-benzodiazepine neurotransmission in an animal model of methamphetamine-induced psychosis.	1999 Mar	10386162
Null mutation of c-fos causes exacerbation of methamphetamine-induced neurotoxicity.	1999 Nov 15	10559418
Methamphetamine-induced neurotoxicity alters locomotor activity, stereotypic behavior, and stimulated dopamine release in the rat.	1999 Oct 15	10516332
Estrogen and progesterone distinctively modulate methamphetamine-induced dopamine and serotonin depletions in C57BL/6J mice.	2000	11129103
Time-course of methamphetamine-induced neurotoxicity in rat caudate-putamen after single-dose treatment.	2000 Apr 28	10773198
Cocaine and methamphetamine: differential addiction rates.	2000 Dec	11130157
Psychiatric comorbidity of methamphetamine dependence in a forensic sample.	2000 Fall	11083165
Exacerbation of psychosis by phenylpropanolamine.	2000 Jun	10831490
Relation between hippocampal gamma waves and behavioral disturbances induced by phencyclidine and methamphetamine.	2000 Jun 15	10840127
Carbamazepine suppresses methamphetamine-induced Fos expression in a regionally specific manner in the rat brain. Possible neural substrates responsible for antimanic effects of mood stabilizers.	2000 May	10731628
Effects of isradipine, a dihydropyridine-class calcium channel antagonist, on D-methamphetamine-induced cognitive and physiological changes in humans.	2000 May	10731625
Age-dependent differential responses of monoaminergic systems to high doses of methamphetamine.	2000 Nov	11032899
Effect of temperature on dopamine transporter function and intracellular accumulation of methamphetamine: implications for methamphetamine-induced dopaminergic neurotoxicity.	2000 Oct 15	11027249
Retrospective study of urinalysis for dl-amphetamine and dl-methamphetamine analysis under current Department of Defense guidelines.	2000 Sep	10999353
Comparison between the role of the neuronal and inducible nitric oxide synthase in methamphetamine-induced neurotoxicity and sensitization.	2000 Sep	11085313
Dopamine deficiency in mice.	2000 Sep	10984662
The effects of single dose of methamphetamine on lipid peroxidation levels in the rat striatum and prefrontal cortex.	2000 Sep	10974615
Anti-apoptotic and apoptotic action of (-)-deprenyl and its metabolites.	2001	11261744
Postnatal maturation of prefrontal pyramidal neurones is sensitive to a single early dose of methamphetamine in gerbils (Meriones unguiculatus).	2001	11261741
Dose-related neuroprotective effects of chronic nicotine in 6-hydroxydopamine treated rats, and loss of neuroprotection in alpha4 nicotinic receptor subunit knockout mice.	2001 Apr	11309235
Sensitized increase of period gene expression in the mouse caudate/putamen caused by repeated injection of methamphetamine.	2001 Apr	11259635
Dose-dependent protective effects of apomorphine against methamphetamine-induced nigrostriatal damage.	2001 Apr 13	11292446
Increased expression of synaptophysin and stathmin mRNAs after methamphetamine administration in rat brain.	2001 Apr 17	11303745
Speed demons.	2001 Apr 2	11299708
Identification of reaction products of methamphetamine and hydrogen peroxide in hair dye and decolorant treatments by high-performance liquid chromatography/mass spectrometry.	2001 Feb	11180300
Long-term changes in basal ganglia function after a neurotoxic regimen of methamphetamine.	2001 Feb	11160639
Peroxynitrite plays a role in methamphetamine-induced dopaminergic neurotoxicity: evidence from mice lacking neuronal nitric oxide synthase gene or overexpressing copper-zinc superoxide dismutase.	2001 Feb	11158245
Drug addicts treatment for ten years in Thanyarak Hospital (1989-1998).	2001 Jan	11281496
Alterations in diurnal and nocturnal locomotor activity in rats treated with a monoamine-depleting regimen of methamphetamine or 3,4-methylenedioxymethamphetamine.	2001 Jan	11271404
[Advanced findings on the molecular mechanisms for behavioral sensitization to psychostimulants].	2001 Jan	11233297
[Amotivational syndrome in organic solvent abusers].	2001 Jan	11233295
Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin.	2001 Jan	11071707
Neurotoxic regimen of methamphetamine produces evidence of behavioral sensitization in the rat.	2001 Jan	11071703
Clozapine, but not haloperidol, reverses social behavior deficit in mice during withdrawal from chronic phencyclidine treatment.	2001 Jan 22	11201068
Plasma and brain methamphetamine concentrations in neonatal rats.	2001 Jan-Feb	11274878
Analysis of amphetamine and congeners in illicit samples by liquid chromatography and capillary electrophoresis.	2001 Mar	11300514
[Pharmacological and physiological effects of ginseng on actions induced by opioids and psychostimulants].	2001 Mar	11288489
Methamphetamine potentiates ischemia/reperfusion insults after transient middle cerebral artery ligation.	2001 Mar	11239201
Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers.	2001 Mar	11229977
IGF-I and bFGF improve dopamine neuron survival and behavioral outcome in parkinsonian rats receiving cultured human fetal tissue strands.	2001 Mar	11170733
Glycine reduces novelty- and methamphetamine-induced locomotor activity in neonatal ventral hippocampal damaged rats.	2001 Mar	11166522
Dopaminergic role in stimulant-induced wakefulness.	2001 Mar 1	11222668
Differences between methamphetamine users and cocaine users in treatment.	2001 Mar 1	11173172
Delta opioid peptide [D-Ala2, D-Leu5]enkephalin causes a near complete blockade of the neuronal damage caused by a single high dose of methamphetamine: examining the role of p53.	2001 Mar 15	11169780
Protective effect of the antioxidant 6-ethoxy-2,2-pentamethylen-1,2-dihydroquinoline (S 33113) in models of cerebral neurodegeneration.	2001 Mar 23	11282113

Patents

Sample Use Guides

In Vivo Use Guide

in rats: 10mg/kg i.p

Route of Administration: Intraperitoneal

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Thu Jul 06 22:59:32 UTC 2023` Edited by `admin` on `Thu Jul 06 22:59:32 UTC 2023`
Record UNII	44RAL3456C
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

METHAMPHETAMINE

Common Name

English

METAMFETAMINE

Official Name

English

J6.362B

Code

English

METHYLAMPHETAMINE

Systematic Name

English

Metamfetamine [WHO-DD]

Common Name

English

metamfetamine [INN]

Common Name

English

NSC-25115

Code

English

METHAMPHETAMINE [VANDF]

Common Name

English

METHAMPHETAMINE [MI]

Common Name

English

(S)-PHENYLMETHYLAMINOPROPANE

Common Name

English

METHAMPHETAMINE [HSDB]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000007883