Identification

Name
Methamphetamine
Accession Number
DB01577
Type
Small Molecule
Groups
Approved, Illicit
Description

Methamphetamine is a psychostimulant and sympathomimetic drug. It is a member of the amphetamine group of sympathomimetic amines. Methamphetamine can induce effects such as euphoria, increased alertness and energy, and enhanced self-esteem. It is a scheduled drug in most countries due to its high potential for addiction and abuse.

Structure
Thumb
Synonyms
  • (+)-(S)-N-alpha-Dimethylphenethylamine
  • (+)-(S)-N-α-dimethylphenethylamine
  • (AlphaS)-N,alpha-dimethylbenzeneethanamine
  • (S)-N,alpha-Dimethylbenzeneethanamine
  • (S)-N,α-dimethylbenzeneethanamine
  • (αS)-N,α-dimethylbenzeneethanamine
  • d-1-phenyl-2-methylaminopropane
  • d-deoxyephedrine
  • d-desoxyephedrine
  • d-N-methylamphetamine
  • d-phenylisopropylmethylamine
  • Dextromethamphetamine
  • Métamfétamine
  • Metamfetamine
  • Metamfetaminum
  • Metanfetamina
  • Methamphetamine
  • Methamphetaminum
  • Methyl-beta-phenylisopropylamine
  • methyl-β-phenylisopropylamine
External IDs
J6.362B / NSC-25115
Product Ingredients
IngredientUNIICASInChI Key
Methamphetamine hydrochloride997F43Z9CV51-57-0TWXDDNPPQUTEOV-FVGYRXGTSA-N
Methamphetamine tartrate7520HJS99O62265-33-2SOSGXQJCXKXQCB-NDAAPVSOSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DesoxynTablet5 mg/1OralLundbeck Inc.1943-12-312013-04-12Us
DesoxynTablet5 mg/1OralRecordati Rare Diseases Inc1943-12-312017-08-19Us
DesoxynTablet5 mg/1OralRecordati Rare Diseases Inc1943-12-31Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Methamphetamine HydrochlorideTablet5 mg/1OralPhysicians Total Care, Inc.2004-08-172005-12-31Us
Methamphetamine HydrochlorideTablet5 mg/1OralMayne Pharma2010-04-26Not applicableUs
Methamphetamine HydrochlorideTablet5 mg/1OralMylan Pharmaceuticals2010-04-262018-10-31Us
Methamphetamine HydrochlorideTablet5 mg/1OralWest-Ward Pharmaceuticals Corp.2016-12-06Not applicableUs
Categories
UNII
44RAL3456C
CAS number
537-46-2
Weight
Average: 149.2328
Monoisotopic: 149.120449485
Chemical Formula
C10H15N
InChI Key
MYWUZJCMWCOHBA-VIFPVBQESA-N
InChI
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
IUPAC Name
methyl[(2S)-1-phenylpropan-2-yl]amine
SMILES
CN[C@@H](C)CC1=CC=CC=C1

Pharmacology

Indication

For the treatment of Attention Deficit Disorder with Hyperactivity (ADHD) and exogenous obesity.

Associated Conditions
Pharmacodynamics

Methamphetamine is a potent central nervous system stimulant which affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions. The acute effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite.

Mechanism of action

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.

TargetActionsOrganism
ASodium-dependent dopamine transporter
negative modulator
Human
ASodium-dependent serotonin transporter
negative modulator
Human
ASodium-dependent noradrenaline transporter
negative modulator
Human
ASynaptic vesicular amine transporter
inhibitor
Human
AChromaffin granule amine transporter
inhibitor
Human
ATrace amine-associated receptor 1
agonist
Human
AAlpha-2A adrenergic receptor
agonist
Human
AAlpha-2B adrenergic receptor
agonist
Human
AAlpha-2C adrenergic receptor
agonist
Human
AAmine oxidase [flavin-containing] A
inhibitor
Human
AAmine oxidase [flavin-containing] B
inhibitor
Human
Absorption

Methamphetamine is rapidly absorbed from the gastrointestinal tract with peak methamphetamine concentrations occurring in 3.13 to 6.3 hours post ingestion. Methamphetamine is also well absorbed following inhalation and following intranasal administration. It is distributed to most parts of the body. Because methamphetamine has a high lipophilicity it is distributed across the blood brain barrier and crosses the placenta.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic. The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine, with the main metabolites being amphetamine (active) and 4-hydroxymethamphetamine. Other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine.

Route of elimination

Excretion occurs primarily in the urine, the rate of which is dependent on urine pH. Between 30-54% of an oral dose is excreted in urine as unchanged methamphetamine and 10-23% as unchanged amphetamine. Following an intravenous dose, 45% is excreted as unchanged parent drug and 7% amphetamine.

Half life

The biological half-life has been reported in the range of 4 to 5 hours.

Clearance
Not Available
Toxicity

Manifestations of acute overdosage with methamphetamine include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning usually terminates in convulsions and coma.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
PRKCA-binding protein---(A;T) / (G;G) / (G;T) / (T;T)T allele / G alleleADR Directly StudiedThe prescence of this polymorphism in PICK1 is associated with increased susceptibility to drug-related psychosis and addiction when using methamphetamine.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Methamphetamine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Methamphetamine is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Methamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Methamphetamine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe risk or severity of adverse effects can be increased when Methamphetamine is combined with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when 3,4-Methylenedioxyamphetamine is combined with Methamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Methamphetamine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Methamphetamine is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Methamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when Methamphetamine is combined with 5-methoxy-N,N-dimethyltryptamine.
Food Interactions
Not Available

References

Synthesis Reference

Nobuyuki Shigetoh, Hiroshi Nakayama, Jinsei Miyazaki, Tadayasu Mitsumata, "Labelling colors for detecting cocaine or methamphetamine, method of preparing the same and detector for cocaine or methamphetamine." U.S. Patent US5571727, issued October, 1981.

US5571727
General References
  1. Schepers RJ, Oyler JM, Joseph RE Jr, Cone EJ, Moolchan ET, Huestis MA: Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers. Clin Chem. 2003 Jan;49(1):121-32. [PubMed:12507968]
  2. McGregor C, Srisurapanont M, Jittiwutikarn J, Laobhripatr S, Wongtan T, White JM: The nature, time course and severity of methamphetamine withdrawal. Addiction. 2005 Sep;100(9):1320-9. [PubMed:16128721]
  3. Bennett BA, Hollingsworth CK, Martin RS, Harp JJ: Methamphetamine-induced alterations in dopamine transporter function. Brain Res. 1998 Jan 26;782(1-2):219-27. [PubMed:9519266]
  4. Hasan AA, Ciancio S: Relationship between amphetamine ingestion and gingival enlargement. Pediatr Dent. 2004 Sep-Oct;26(5):396-400. [PubMed:15460293]
  5. Shaner JW: Caries associated with methamphetamine abuse. J Mich Dent Assoc. 2002 Sep;84(9):42-7. [PubMed:12271905]
External Links
Human Metabolome Database
HMDB0015517
KEGG Compound
C07164
PubChem Compound
10836
PubChem Substance
46508541
ChemSpider
10379
BindingDB
50359499
ChEBI
6809
ChEMBL
CHEMBL1201201
Therapeutic Targets Database
DAP001496
PharmGKB
PA450403
HET
B40
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Methamphetamine
ATC Codes
N06BA03 — Metamfetamine
PDB Entries
3gkz / 4gqp / 4xp6
FDA label
Download (55.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceMethamphetamine Abuse / Methamphetamine Dependence1
0CompletedHealth Services ResearchMethamphetamine Dependence1
1CompletedBasic ScienceMethamphetamine Abuse / Methamphetamine Dependence1
1RecruitingTreatmentMethamphetamine Use Disorder1
2RecruitingBasic ScienceMethamphetamine Abuse / Substance Use Disorder (SUD)1
Not AvailableCompletedBasic ScienceSubstance Abuse1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Abbott Laboratories Ltd.
  • Chattem Chemicals Inc.
  • Lundbeck Inc.
  • Mylan
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
TabletOral5 mg/1
Prices
Unit descriptionCostUnit
Desoxyn 5 mg tablet5.1USD tablet
Methamphetamine 5 mg tablet3.6USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.07HANSCH,C ET AL. (1995)
pKa9.87 (at 25 °C)PERRIN,DD (1965)
Predicted Properties
PropertyValueSource
Water Solubility0.928 mg/mLALOGPS
logP2.23ALOGPS
logP2.24ChemAxon
logS-2.2ALOGPS
pKa (Strongest Basic)10.21ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity48.48 m3·mol-1ChemAxon
Polarizability18.04 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.993
Blood Brain Barrier+0.9695
Caco-2 permeable+0.8675
P-glycoprotein substrateNon-substrate0.6682
P-glycoprotein inhibitor INon-inhibitor0.9338
P-glycoprotein inhibitor IINon-inhibitor0.9816
Renal organic cation transporterNon-inhibitor0.736
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateNon-substrate0.7
CYP450 1A2 substrateNon-inhibitor0.6771
CYP450 2C9 inhibitorNon-inhibitor0.957
CYP450 2D6 inhibitorInhibitor0.8695
CYP450 2C19 inhibitorNon-inhibitor0.7754
CYP450 3A4 inhibitorNon-inhibitor0.9536
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9095
Ames testNon AMES toxic0.9306
CarcinogenicityNon-carcinogens0.8161
BiodegradationNot ready biodegradable0.7508
Rat acute toxicity3.1862 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9443
hERG inhibition (predictor II)Non-inhibitor0.9118
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (2.96 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-9000000000-fd0454cafd58d60de713
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0gb9-2900000000-9f47787fb23e13a87dad
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0900000000-7337ca7928cea10bffe5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udl-5900000000-03d47250c7a980a66e20
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9300000000-d10984417cc7279a776b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-ba626750e38f88879a89
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-3e56ce6f6bf92f4b0a14
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-4095966beeb0165843c9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udi-0900000000-7337ca7928cea10bffe5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0udl-5900000000-bb1f4cbf0ac7cca4d691
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9300000000-6e88a7d0ffb252a513da
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-70ddbc2127d9ecc43ec0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-faa0136ac65ec9065e49
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-9000000000-ce6e9f98d322c724f026
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0gb9-2900000000-753b4591b9e358e01e68
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kf-9800000000-94af1bb67acf7028de89
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kf-9800000000-904b385cb2c1370393d6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9200000000-49618d55cba0c2470ba6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9000000000-3167ad4af9af7ec20657
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9000000000-351c5861a20ce31f40a9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-9000000000-cd1055202e84beaff361

Taxonomy

Description
This compound belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenethylamines
Direct Parent
Amphetamines and derivatives
Alternative Parents
Phenylpropanes / Aralkylamines / Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Amphetamine or derivatives / Phenylpropane / Aralkylamine / Secondary amine / Secondary aliphatic amine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Amine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
amphetamines (CHEBI:6809)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Negative modulator
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Escubedo E, Camarasa J, Chipana C, Garcia-Rates S, Pubill D: Involvement of nicotinic receptors in methamphetamine- and MDMA-induced neurotoxicity: pharmacological implications. Int Rev Neurobiol. 2009;88:121-66. doi: 10.1016/S0074-7742(09)88006-9. [PubMed:19897077]
  2. Lott DC, Kim SJ, Cook EH Jr, de Wit H: Dopamine transporter gene associated with diminished subjective response to amphetamine. Neuropsychopharmacology. 2005 Mar;30(3):602-9. [PubMed:15602501]
  3. Fone KC, Nutt DJ: Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder. Curr Opin Pharmacol. 2005 Feb;5(1):87-93. [PubMed:15661631]
  4. Miller GM, Verrico CD, Jassen A, Konar M, Yang H, Panas H, Bahn M, Johnson R, Madras BK: Primate trace amine receptor 1 modulation by the dopamine transporter. J Pharmacol Exp Ther. 2005 Jun;313(3):983-94. Epub 2005 Mar 11. [PubMed:15764732]
  5. Garcia BG, Wei Y, Moron JA, Lin RZ, Javitch JA, Galli A: Akt is essential for insulin modulation of amphetamine-induced human dopamine transporter cell-surface redistribution. Mol Pharmacol. 2005 Jul;68(1):102-9. Epub 2005 Mar 28. [PubMed:15795321]
  6. Madras BK, Miller GM, Fischman AJ: The dopamine transporter and attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005 Jun 1;57(11):1397-409. Epub 2005 Jan 5. [PubMed:15950014]
  7. Kahlig KM, Binda F, Khoshbouei H, Blakely RD, McMahon DG, Javitch JA, Galli A: Amphetamine induces dopamine efflux through a dopamine transporter channel. Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3495-500. Epub 2005 Feb 22. [PubMed:15728379]
  8. Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR: New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. 2007;47:681-98. [PubMed:17209801]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Negative modulator
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Numachi Y, Ohara A, Yamashita M, Fukushima S, Kobayashi H, Hata H, Watanabe H, Hall FS, Lesch KP, Murphy DL, Uhl GR, Sora I: Methamphetamine-induced hyperthermia and lethal toxicity: role of the dopamine and serotonin transporters. Eur J Pharmacol. 2007 Oct 31;572(2-3):120-8. Epub 2007 Jun 27. [PubMed:17673199]
  2. Tellez R, Rocha L, Castillo C, Meneses A: Autoradiographic study of serotonin transporter during memory formation. Behav Brain Res. 2010 Sep 1;212(1):12-26. doi: 10.1016/j.bbr.2010.03.015. Epub 2010 Mar 11. [PubMed:20226815]
  3. Sora I, Li B, Fumushima S, Fukui A, Arime Y, Kasahara Y, Tomita H, Ikeda K: Monoamine transporter as a target molecule for psychostimulants. Int Rev Neurobiol. 2009;85:29-33. doi: 10.1016/S0074-7742(09)85003-4. [PubMed:19607959]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Negative modulator
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR: New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. 2007;47:681-98. [PubMed:17209801]
  2. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [PubMed:15955613]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles...
Gene Name
SLC18A2
Uniprot ID
Q05940
Uniprot Name
Synaptic vesicular amine transporter
Molecular Weight
55712.075 Da
References
  1. Horton DB, Siripurapu KB, Norrholm SD, Culver JP, Hojahmat M, Beckmann JS, Harrod SB, Deaciuc AG, Bardo MT, Crooks PA, Dwoskin LP: meso-Transdiene analogs inhibit vesicular monoamine transporter-2 function and methamphetamine-evoked dopamine release. J Pharmacol Exp Ther. 2011 Mar;336(3):940-51. doi: 10.1124/jpet.110.175117. Epub 2010 Dec 21. [PubMed:21177475]
  2. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [PubMed:15955613]
  3. Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A: Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. J Neurosci. 1995 May;15(5 Pt 2):4102-8. [PubMed:7751968]
  4. Yasumoto S, Tamura K, Karasawa J, Hasegawa R, Ikeda K, Yamamoto T, Yamamoto H: Inhibitory effect of selective serotonin reuptake inhibitors on the vesicular monoamine transporter 2. Neurosci Lett. 2009 May 1;454(3):229-32. doi: 10.1016/j.neulet.2009.03.049. Epub 2009 Mar 18. [PubMed:19429089]
  5. Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR: New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. 2007;47:681-98. [PubMed:17209801]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin transmembrane transporter activity
Specific Function
Involved in the transport of biogenic monoamines, such as serotonin, from the cytoplasm into the secretory vesicles of neuroendocrine and endocrine cells.
Gene Name
SLC18A1
Uniprot ID
P54219
Uniprot Name
Chromaffin granule amine transporter
Molecular Weight
56256.71 Da
References
  1. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [PubMed:15955613]
  2. Henry JP, Sagne C, Bedet C, Gasnier B: The vesicular monoamine transporter: from chromaffin granule to brain. Neurochem Int. 1998 Mar;32(3):227-46. [PubMed:9587917]
  3. Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR: New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol. 2007;47:681-98. [PubMed:17209801]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Trace-amine receptor activity
Specific Function
Receptor for trace amines, including beta-phenylethylamine (b-PEA), p-tyramine (p-TYR), octopamine and tryptamine, with highest affinity for b-PEA and p-TYR. Unresponsive to classical biogenic amin...
Gene Name
TAAR1
Uniprot ID
Q96RJ0
Uniprot Name
Trace amine-associated receptor 1
Molecular Weight
39091.34 Da
References
  1. Grandy DK: Trace amine-associated receptor 1-Family archetype or iconoclast? Pharmacol Ther. 2007 Dec;116(3):355-90. Epub 2007 Jul 17. [PubMed:17888514]
  2. Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C: Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):8966-71. Epub 2001 Jul 17. [PubMed:11459929]
  3. Reese EA, Bunzow JR, Arttamangkul S, Sonders MS, Grandy DK: Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and para-hydroxyamphetamine. J Pharmacol Exp Ther. 2007 Apr;321(1):178-86. Epub 2007 Jan 11. [PubMed:17218486]
  4. Xie Z, Westmoreland SV, Bahn ME, Chen GL, Yang H, Vallender EJ, Yao WD, Madras BK, Miller GM: Rhesus monkey trace amine-associated receptor 1 signaling: enhancement by monoamine transporters and attenuation by the D2 autoreceptor in vitro. J Pharmacol Exp Ther. 2007 Apr;321(1):116-27. Epub 2007 Jan 18. [PubMed:17234900]
  5. Wolinsky TD, Swanson CJ, Smith KE, Zhong H, Borowsky B, Seeman P, Branchek T, Gerald CP: The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia. Genes Brain Behav. 2007 Oct;6(7):628-39. Epub 2006 Dec 21. [PubMed:17212650]
  6. Xie Z, Miller GM: Trace amine-associated receptor 1 is a modulator of the dopamine transporter. J Pharmacol Exp Ther. 2007 Apr;321(1):128-36. Epub 2007 Jan 18. [PubMed:17234899]
  7. Miller GM, Verrico CD, Jassen A, Konar M, Yang H, Panas H, Bahn M, Johnson R, Madras BK: Primate trace amine receptor 1 modulation by the dopamine transporter. J Pharmacol Exp Ther. 2005 Jun;313(3):983-94. Epub 2005 Mar 11. [PubMed:15764732]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Jeng CH, Wang Y: Methamphetamine modulates GABA-induced electrophysiological depression by alternating noradrenergic actions in cerebellar Purkinje neurons. Psychopharmacology (Berl). 1998 Mar;136(2):132-8. [PubMed:9551769]
  2. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [PubMed:15955613]
  3. Nishio M, Kanda Y, Mizuno K, Watanabe Y: Methamphetamine increases the hippocampal alpha(2A)-adrenergic receptor and Galpha(o) in mice. Neurosci Lett. 2002 Dec 16;334(3):145-8. [PubMed:12453616]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Epinephrine binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. Jeng CH, Wang Y: Methamphetamine modulates GABA-induced electrophysiological depression by alternating noradrenergic actions in cerebellar Purkinje neurons. Psychopharmacology (Berl). 1998 Mar;136(2):132-8. [PubMed:9551769]
  2. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [PubMed:15955613]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. Jeng CH, Wang Y: Methamphetamine modulates GABA-induced electrophysiological depression by alternating noradrenergic actions in cerebellar Purkinje neurons. Psychopharmacology (Berl). 1998 Mar;136(2):132-8. [PubMed:9551769]
  2. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [PubMed:15955613]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin binding
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOA
Uniprot ID
P21397
Uniprot Name
Amine oxidase [flavin-containing] A
Molecular Weight
59681.27 Da
References
  1. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [PubMed:15955613]
  2. Ulus IH, Maher TJ, Wurtman RJ: Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors. Biochem Pharmacol. 2000 Jun 15;59(12):1611-21. [PubMed:10799660]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Primary amine oxidase activity
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOB
Uniprot ID
P27338
Uniprot Name
Amine oxidase [flavin-containing] B
Molecular Weight
58762.475 Da
References
  1. Sulzer D, Sonders MS, Poulsen NW, Galli A: Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol. 2005 Apr;75(6):406-33. [PubMed:15955613]
  2. Ulus IH, Maher TJ, Wurtman RJ: Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors. Biochem Pharmacol. 2000 Jun 15;59(12):1611-21. [PubMed:10799660]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Ramamoorthy Y, Tyndale RF, Sellers EM: Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates. Pharmacogenetics. 2001 Aug;11(6):477-87. [PubMed:11505218]
  3. Lin LY, Di Stefano EW, Schmitz DA, Hsu L, Ellis SW, Lennard MS, Tucker GT, Cho AK: Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6. Drug Metab Dispos. 1997 Sep;25(9):1059-64. [PubMed:9311621]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Toxin transporter activity
Specific Function
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Wu X, Kekuda R, Huang W, Fei YJ, Leibach FH, Chen J, Conway SJ, Ganapathy V: Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998 Dec 4;273(49):32776-86. [PubMed:9830022]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Wu X, Prasad PD, Leibach FH, Ganapathy V: cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun. 1998 May 29;246(3):589-95. [PubMed:9618255]
  2. Wu X, Huang W, Prasad PD, Seth P, Rajan DP, Leibach FH, Chen J, Conway SJ, Ganapathy V: Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther. 1999 Sep;290(3):1482-92. [PubMed:10454528]

Drug created on August 29, 2007 08:51 / Updated on November 02, 2018 09:07