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Record Information
Version2.0
Creation Date2009-07-21 20:28:53 UTC
Update Date2014-12-24 20:25:56 UTC
Accession NumberT3D3052
Identification
Common NameMethamphetamine
ClassSmall Molecule
DescriptionMethamphetamine 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.
Compound Type
  • Adrenergic Agent
  • Adrenergic Uptake Inhibitor
  • Amine
  • Central Nervous System Stimulant
  • Dopamine Agent
  • Dopamine Uptake Inhibitor
  • Drug
  • Metabolite
  • Organic Compound
  • Sympathomimetic
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+ )-methylamphetamine
(+)-(S)-deoxyephedrine
(+)-(S)-N-alpha-dimethylphenethylamine
(+)-(S)-N-α-dimethylphenethylamine
(+)-2-(N-Methylamino)-1-phenylpropane
(+)-methamphetamine
(+)-methylamphetamine
(+)-N,alpha-dimethyl-beta-phenylethylamine
(+)-N,alpha-dimethylphenethylamine
(+)-N-methylamphetamine
(2S)-N-methyl-1-phenylpropan-2-amine
(AlphaS)-N,alpha-dimethylbenzeneethanamine
(S)-(+)-deoxyephedrine
(S)-(+)-methamphetamine
(S)-(+)-N,alpha,dimethylphenethylamine
(S)-methamphetamine
(S)-methylamphetamine
(S)-N,alpha-dimethylbenzeneethanamine
(S)-N,alpha-dimethylbenzeneethanoamine
(S)-N,α-dimethylbenzeneethanamine
(αS)-N,α-dimethylbenzeneethanamine
1-Phenyl-2-methylaminopropane
2S-(+)-Methamphetamine
D-(S)-Methamphetamine
D-1-Phenyl-2-methylaminopropane
D-Deoxyephedrine
D-Desoxyephedrine
D-Methamphetamine
D-Methylamphetamine
D-N,alpha-Dimethylphenethylamine
D-N-Methylamphetamine
D-Phenylisopropylmethylamine
Desoxyephedrine hydrochloride
Desoxyn
Dextromethamphetamine
Ice
L-Methamphetamine
Métamfétamine
Metamfetaminum
Metamphetamine
Metanfetamina
Meth
Methamphetaminum
Methyl-beta-phenylisopropylamine
methyl-β-phenylisopropylamine
Methylamphetamine
N-Methyl-1-phenyl-2-propanamine
N-Methyl-beta-phenylisopropylamine
N-Methylamphetamine
S-(+)-Methamphetamine
Chemical FormulaC10H15N
Average Molecular Mass149.233 g/mol
Monoisotopic Mass149.120 g/mol
CAS Registry Number537-46-2
IUPAC Namemethyl[(2S)-1-phenylpropan-2-yl]amine
Traditional Namemeth
SMILES[H][C@](C)(CC1=CC=CC=C1)NC
InChI IdentifierInChI=1S/C10H15N/c1-9(11-2)8-10-6-4-3-5-7-10/h3-7,9,11H,8H2,1-2H3/t9-/m0/s1
InChI KeyInChIKey=MYWUZJCMWCOHBA-VIFPVBQESA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenethylamines
Direct ParentAmphetamines and derivatives
Alternative Parents
Substituents
  • Amphetamine or derivatives
  • Phenylpropane
  • Aralkylamine
  • Secondary amine
  • Secondary aliphatic amine
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Kidney
  • Liver
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility9.28e-01 g/L
LogP2.07
Predicted Properties
PropertyValueSource
Water Solubility0.93 g/LALOGPS
logP2.23ALOGPS
logP2.24ChemAxon
logS-2.2ALOGPS
pKa (Strongest Basic)10.21ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity48.48 m³·mol⁻¹ChemAxon
Polarizability18.04 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9100000000-d5c137de90ac4540f8bbJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0gb9-2900000000-9f47787fb23e13a87dadJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0900000000-7337ca7928cea10bffe5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udl-5900000000-03d47250c7a980a66e20JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-9300000000-d10984417cc7279a776bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-9000000000-ba626750e38f88879a89JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-9000000000-3e56ce6f6bf92f4b0a14JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-9000000000-4095966beeb0165843c9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0900000000-7337ca7928cea10bffe5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udl-5900000000-bb1f4cbf0ac7cca4d691JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-9300000000-6e88a7d0ffb252a513daJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-9000000000-70ddbc2127d9ecc43ec0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-9000000000-faa0136ac65ec9065e49JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0006-9000000000-ce6e9f98d322c724f026JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0gb9-2900000000-753b4591b9e358e01e68JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00kf-9800000000-94af1bb67acf7028de89JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00kf-9800000000-904b385cb2c1370393d6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-9200000000-49618d55cba0c2470ba6JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-9000000000-3167ad4af9af7ec20657JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-9000000000-351c5861a20ce31f40a9JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0900000000-6ca41b91a4dd107137f5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0uxr-3900000000-7fa23fc8e2e96d14abccJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9300000000-104f35aae3c1bcbc7887JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0900000000-503d557b64d8fcd09a36JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-1900000000-d34387a31168c299ab03JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ku6-9400000000-3a9b55d0b53a10725f67JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0a4i-9000000000-fd0454cafd58d60de713JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureMethamphetamine 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.
Mechanism of ToxicityMethamphetamine 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.
MetabolismHepatic. 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.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of Attention Deficit Disorder with Hyperactivity (ADHD) and exogenous obesity.
Minimum Risk LevelNot Available
Health EffectsUsing large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.
SymptomsManifestations 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.
TreatmentManagement of acute methamphetamine intoxication is largely symptomatic and includes gastric evacuation, administration of activated charcoal, and sedation. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendations in this regard. Acidification of urine increases methamphetamine excretion, but is believed to increase risk of acute renal failure if myoglobinuria is present. Intravenous phentolamine has been suggested for possible acute, severe hypertension, if this complicates methamphetamine overdosage. Usually a gradual drop in blood pressure will result when sufficient sedation has been achieved. Chlorpromazine has been reported to be useful in decreasing CNS stimulation and sympathomimetic effects. (7)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01577
HMDB IDHMDB15517
PubChem Compound ID10836
ChEMBL IDCHEMBL1201201
ChemSpider ID10379
KEGG IDC07164
UniProt IDNot Available
OMIM ID
ChEBI ID6809
BioCyc IDNot Available
CTD IDNot Available
Stitch IDMethamphetamine
PDB IDB40
ACToR IDNot Available
Wikipedia LinkMethamphetamine
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.

MSDST3D3052.pdf
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. [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. [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. [9519266 ]
  4. Hasan AA, Ciancio S: Relationship between amphetamine ingestion and gingival enlargement. Pediatr Dent. 2004 Sep-Oct;26(5):396-400. [15460293 ]
  5. Shaner JW: Caries associated with methamphetamine abuse. J Mich Dent Assoc. 2002 Sep;84(9):42-7. [12271905 ]
  6. Ko BJ, Suh S, Suh YJ, In MK, Kim SH, Kim JH: (1S,2S)-1-Methylamino-1-phenyl-2-chloropropane: Route specific marker impurity of methamphetamine synthesized from ephedrine via chloroephedrine. Forensic Sci Int. 2012 Sep 10;221(1-3):92-7. doi: 10.1016/j.forsciint.2012.04.008. Epub 2012 May 2. [22554873 ]
  7. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

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
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. [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. [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. [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. [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. [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. [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. [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. [17209801 ]
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 amines, such as epinephrine and histamine and only partially activated by dopamine and serotonine. Trace amines are biogenic amines present in very low levels in mammalian tissues. Although some trace amines have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Trace amines are likely to be involved in a variety of physiological functions that have yet to be fully understood. The signal transduced by this receptor is mediated by the G(s)-class of G-proteins which activate adenylate cyclase.
Gene Name:
TAAR1
Uniprot ID:
Q96RJ0
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. [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. [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. [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. [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. [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. [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. [15764732 ]
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. Requisite for vesicular amine storage prior to secretion via exocytosis.
Gene Name:
SLC18A2
Uniprot ID:
Q05940
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. [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. [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. [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. [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. [17209801 ]
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Battaglia G, Fornai F, Busceti CL, Lembo G, Nicoletti F, De Blasi A: Alpha-1B adrenergic receptor knockout mice are protected against methamphetamine toxicity. J Neurochem. 2003 Jul;86(2):413-21. [12871582 ]
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 oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Gene Name:
ADRA2A
Uniprot ID:
P08913
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. [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. [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. [12453616 ]
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
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. [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. [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. [17209801 ]
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 the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
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. [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. [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. [19607959 ]
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
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 > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
Gene Name:
ADRA2B
Uniprot ID:
P18089
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. [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. [15955613 ]
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
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. [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. [15955613 ]
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 tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.
Gene Name:
MAOA
Uniprot ID:
P21397
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. [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. [10799660 ]
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 tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
Gene Name:
MAOB
Uniprot ID:
P27338
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. [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. [10799660 ]
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
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. [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. [15955613 ]
General Function:
Opioid receptor activity
Specific Function:
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
Gene Name:
SIGMAR1
Uniprot ID:
Q99720
Molecular Weight:
25127.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory8.32 uMNot AvailableBindingDB 50359499
References
  1. Glennon RA, Smith JD, Ismaiel AM, el-Ashmawy M, Battaglia G, Fischer JB: Identification and exploitation of the sigma-opiate pharmacophore. J Med Chem. 1991 Mar;34(3):1094-8. [1848295 ]