You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version5.0
StatusDetected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2021-09-14 15:48:17 UTC
HMDB IDHMDB0014339
Secondary Accession Numbers
  • HMDB14339
Metabolite Identification
Common NameTramadol
DescriptionTramadol is only found in individuals that have used or taken this drug. It is a narcotic analgesic proposed for moderate to severe pain. It may be habituating (PubChem). Tramadol and its O-desmethyl metabolite (M1) are selective, weak OP3-receptor agonists. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. As the effector system is adenylate cyclase and cAMP is located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is inhibited. The analgesic properties of tramadol can be attributed to norepinephrine and serotonin reuptake blockade in the CNS, which inhibits pain transmission in the spinal cord. The (+) enantiomer has a higher affinity for the OP3 receptor and preferentially inhibits serotonin uptake and enhances serotonin release. The (-) enantiomer preferentially inhibits norepinephrine reuptake by stimulating alpha(2)-adrenergic receptors.
Structure
Data?1582753167
Synonyms
ValueSource
(+)-TramadolChEBI
(+)-trans-2-(Dimethylaminomethyl)-1-(m-methoxyphenyl)cyclohexanolChEBI
AmandaKegg
1a Brand OF tramadol hydrochlorideHMDB
ASTA medica brand OF tramadol hydrochlorideHMDB
AbZ brand OF tramadol hydrochlorideHMDB
AdolontaHMDB
Bayvit brand OF tramadol hydrochlorideHMDB
Bexal brand OF tramadol hydrochlorideHMDB
Dolorgiet brand OF tramadol hydrochlorideHMDB
Edigen brand OF tramadol hydrochlorideHMDB
Hexal brand OF tramadol hydrochlorideHMDB
Lindopharm brand OF tramadol hydrochlorideHMDB
MTW Brand OF tramadol hydrochlorideHMDB
MTW TramadolHMDB
Mabo brand OF tramadol hydrochlorideHMDB
Q-Pharm brand OF tramadol hydrochlorideHMDB
Rowa brand OF tramadol hydrochlorideHMDB
Theraplix brand OF tramadol hydrochlorideHMDB
Tradol-purenHMDB
TradolPurenHMDB
Trama 1a pharmaHMDB
Trama KDHMDB
Tramadol asta medicaHMDB
Tramadol bexalHMDB
Tramadol edigenHMDB
Tramadol ratiopharmHMDB
TramadolHamelnHMDB
UltramHMDB
ZydolHMDB
Alpharma brand OF tramadol hydrochlorideHMDB
BiodalgicHMDB
Byk brand OF tramadol hydrochlorideHMDB
Ciclum brand OF tramadol hydrochlorideHMDB
Cinfa brand OF tramadol hydrochlorideHMDB
Clonmel brand OF tramadol hydrochlorideHMDB
ContramalHMDB
Elerte brand OF tramadol hydrochlorideHMDB
Expanscience brand OF tramadol hydrochlorideHMDB
Hameln brand OF tramadol hydrochlorideHMDB
JutadolHMDB
Knoll brand OF tramadol hydrochlorideHMDB
Krewel brand OF tramadol hydrochlorideHMDB
MTWTramadolHMDB
Medix brand OF tramadol hydrochlorideHMDB
TAD brand OF tramadol hydrochlorideHMDB
TheradolHMDB
TiralHMDB
Tradol purenHMDB
TradonalHMDB
Trama-dorschHMDB
TramaDorschHMDB
TramadinHMDB
TramadocHMDB
Tramadol 1aHMDB
Tramadol alHMDB
Tramadol bayvitHMDB
Tramadol maboHMDB
Tramadol PBHMDB
Tramadol acisHMDB
TramadolDolgitHMDB
TramadolorHMDB
TramageticHMDB
TramagitHMDB
Zambon brand OF tramadol hydrochlorideHMDB
ZamudolHMDB
ZytramHMDB
Betapharm brand OF tramadol hydrochlorideHMDB
Aliud brand OF tramadol hydrochlorideHMDB
AmadolHMDB
CSL Brand OF tramadol hydrochlorideHMDB
Christiaens brand OF tramadol hydrochlorideHMDB
Erempharma brand OF tramadol hydrochlorideHMDB
Grunenthal brand OF tramadol hydrochlorideHMDB
Heumann brand OF tramadol hydrochlorideHMDB
Juta brand OF tramadol hydrochlorideHMDB
Kern brand OF tramadol hydrochlorideHMDB
Lakeside brand OF tramadol hydrochlorideHMDB
Lichtenstein brand OF tramadol hydrochlorideHMDB
Mundipharma brand OF tramadol hydrochlorideHMDB
NobliganHMDB
Ortho brand OF tramadol hydrochlorideHMDB
Ranitidin 1a pharmaHMDB
Ratiopharm brand OF tramadol hydrochlorideHMDB
Searle brand OF tramadol hydrochlorideHMDB
Stadapharm brand OF tramadol hydrochlorideHMDB
TakadolHMDB
TopalgicHMDB
TradolHMDB
TralgiolHMDB
Trama abzHMDB
Tramadol hydrochlorideHMDB
Tramadol normonHMDB
Tramadol-hamelnHMDB
Tramadol-ratiopharmHMDB
TramadolratiopharmHMDB
TramakeHMDB
TrasedalHMDB
Viatris brand OF tramadolHMDB
Acis brand OF tramadol hydrochlorideHMDB
Allphar brand OF tramadol hydrochlorideHMDB
Antigen brand OF tramadol hydrochlorideHMDB
Azupharma brand OF tramadol hydrochlorideHMDB
Basics brand OF tramadol hydrochlorideHMDB
Biocodex brand OF tramadol hydrochlorideHMDB
BiokanolHMDB
Docpharm brand OF tramadol hydrochlorideHMDB
Janssen brand OF tramadol hydrochlorideHMDB
Kade brand OF tramadol hydrochlorideHMDB
MTW-TramadolHMDB
Merck dura brand OF tramadol hydrochlorideHMDB
Normon brand OF tramadol hydrochlorideHMDB
ProntofortHMDB
Q Pharm brand OF tramadol hydrochlorideHMDB
Trama dorschHMDB
TramabetaHMDB
Tramadol basicsHMDB
Tramadol cinfaHMDB
Tramadol dolgitHMDB
Tramadol hamelnHMDB
Tramadol heumannHMDB
Tramadol kernHMDB
Tramadol lichtensteinHMDB
Tramadol lindoHMDB
Tramadol stadaHMDB
Tramadol viatris brandHMDB
Tramadol-dolgitHMDB
TramaduraHMDB
TramalHMDB
TramexHMDB
TramundinHMDB
Xymel 50HMDB
ZumalgicHMDB
Chemical FormulaC16H25NO2
Average Molecular Weight263.3752
Monoisotopic Molecular Weight263.188529049
IUPAC Name(1R,2R)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexan-1-ol
Traditional Nametramadol
CAS Registry Number27203-92-5
SMILES
COC1=CC=CC(=C1)[C@@]1(O)CCCC[C@@H]1CN(C)C
InChI Identifier
InChI=1S/C16H25NO2/c1-17(2)12-14-7-4-5-10-16(14,18)13-8-6-9-15(11-13)19-3/h6,8-9,11,14,18H,4-5,7,10,12H2,1-3H3/t14-,16+/m1/s1
InChI KeyTVYLLZQTGLZFBW-ZBFHGGJFSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof.
KingdomOrganic compounds
Super ClassBenzenoids
ClassPhenol ethers
Sub ClassAnisoles
Direct ParentAnisoles
Alternative Parents
Substituents
  • Phenoxy compound
  • Anisole
  • Methoxybenzene
  • Alkyl aryl ether
  • Cyclohexanol
  • Aralkylamine
  • Monocyclic benzene moiety
  • Tertiary alcohol
  • Cyclic alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ether
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Alcohol
  • Organic oxygen compound
  • Amine
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
  • 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol (CHEBI:75725 )
Ontology
Physiological effect

Health effect:

Disposition

Source:

Route of exposure:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Environmental role:

Industrial application:

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point180 - 181 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.75 g/LNot Available
LogP2.4Not Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.75 g/LALOGPS
logP2.71ALOGPS
logP2.45ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)13.8ChemAxon
pKa (Strongest Basic)9.23ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area32.7 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity78.27 m³·mol⁻¹ChemAxon
Polarizability30.45 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted Spectral Properties

Collision Cross Sections

NameAdductTypeData SourceValueReference
DeepCCS[M+H]+ExperimentalCBM161.430932474
DarkChem[M+H]+PredictedNot Available164.05131661259
DarkChem[M-H]-PredictedNot Available162.9431661259

Retention Indices

Underivatized

Not Available

Derivatized

DerivativeValueReference
Tramadol,1TMS,#11946.0408https://arxiv.org/abs/1905.12712
Tramadol,1TBDMS,#12191.4917https://arxiv.org/abs/1905.12712
Spectra

GC-MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9650000000-250d842ef062333281702017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-05fr-5193000000-dd2e84f70a47d0634c432017-10-06View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0a4i-9010000000-ffea37e400f0860f2e7f2014-09-20View Spectrum

LC-MS/MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-03di-0090000000-1550dc2447717d7d87282017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03di-0090000000-7850be0ba78033f1f6772017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03di-0090000000-62a3c5cb6717bff20e2c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-05fs-0930000000-b8297a71c45e9630f6c02017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-05fr-0900000000-f650c49b70db20869d0f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0adl-0900000000-b17dfc32e2eb57efaf422017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-0090000000-c35bec467cfec28511fb2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-03di-1090000000-9ca08dcdc5a2027bcb032017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-9030000000-469467d2583e7202d89f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-9000000000-89f055b497c88cdc5e792017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-9000000000-1922068301c6d3b4f4572017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-9000000000-1922068301c6d3b4f4572017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-9000000000-5a9396f20ce15b9c08ba2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-03di-1090000000-e040861e9fa18a8f44a52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-9030000000-fa1522b6a491e6da41c92017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-9000000000-8ab0ebc3ceff7c5e5ce52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-9000000000-7645dc9b29d8b28674952017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-9000000000-70cad0a31ff2d57bab812017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-9000000000-bf1b2c15c6511355c9e12017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-0090000000-02e5642feacadbc07dba2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0abi-0900000000-5e83a9ee1a223ef369052017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00di-0900000000-56f60436c6df4aeb65152017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-0090000000-1336e1f66542750cc1de2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-0090000000-0f15435bd2e7f629a8982017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-0090000000-1550dc2447717d7d87282017-09-14View Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00193 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00193 details
UrineDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00193
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID31105
KEGG Compound IDC07153
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTramadol
METLIN IDNot Available
PubChem Compound33741
PDB IDNot Available
ChEBI ID75725
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Dayer P, Desmeules J, Collart L: [Pharmacology of tramadol]. Drugs. 1997;53 Suppl 2:18-24. [PubMed:9190321 ]
  2. Gobel H, Stadler T: [Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine]. Drugs. 1997;53 Suppl 2:34-9. [PubMed:9190323 ]
  3. Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, Donofrio P, Cornblath D, Sachdeo R, Siu CO, Kamin M: Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology. 1998 Jun;50(6):1842-6. [PubMed:9633738 ]
  4. Harati Y, Gooch C, Swenson M, Edelman SV, Greene D, Raskin P, Donofrio P, Cornblath D, Olson WH, Kamin M: Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy. J Diabetes Complications. 2000 Mar-Apr;14(2):65-70. [PubMed:10959067 ]
  5. Boureau F, Legallicier P, Kabir-Ahmadi M: Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial. Pain. 2003 Jul;104(1-2):323-31. [PubMed:12855342 ]
  6. (). FDA label . .

Only showing the first 10 proteins. There are 11 proteins in total.

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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 ]
General function:
Involved in monooxygenase 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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
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 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular weight:
56277.81
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 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Highly stereoselective. receptor for enkephalins
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular weight:
40412.3
References
  1. Wentland MP, Lou R, Lu Q, Bu Y, VanAlstine MA, Cohen DJ, Bidlack JM: Syntheses and opioid receptor binding properties of carboxamido-substituted opioids. Bioorg Med Chem Lett. 2009 Jan 1;19(1):203-8. doi: 10.1016/j.bmcl.2008.10.134. Epub 2008 Nov 7. [PubMed:19027293 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular weight:
44778.9
References
  1. Gillen C, Haurand M, Kobelt DJ, Wnendt S: Affinity, potency and efficacy of tramadol and its metabolites at the cloned human mu-opioid receptor. Naunyn Schmiedebergs Arch Pharmacol. 2000 Aug;362(2):116-21. [PubMed:10961373 ]
  2. Potschka H, Friderichs E, Loscher W: Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy. Br J Pharmacol. 2000 Sep;131(2):203-12. [PubMed:10991912 ]
  3. Raffa RB, Friderichs E, Reimann W, Shank RP, Codd EE, Vaught JL: Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an 'atypical' opioid analgesic. J Pharmacol Exp Ther. 1992 Jan;260(1):275-85. [PubMed:1309873 ]
  4. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [PubMed:15509185 ]
  5. Ide S, Minami M, Ishihara K, Uhl GR, Sora I, Ikeda K: Mu opioid receptor-dependent and independent components in effects of tramadol. Neuropharmacology. 2006 Sep;51(3):651-8. Epub 2006 Jun 21. [PubMed:16793069 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Minami K, Uezono Y, Ueta Y: Pharmacological aspects of the effects of tramadol on G-protein coupled receptors. J Pharmacol Sci. 2007 Mar;103(3):253-60. [PubMed:17380034 ]
  8. Frink MC, Hennies HH, Englberger W, Haurand M, Wilffert B: Influence of tramadol on neurotransmitter systems of the rat brain. Arzneimittelforschung. 1996 Nov;46(11):1029-36. [PubMed:8955860 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular weight:
51820.7
References
  1. Ogata J, Minami K, Uezono Y, Okamoto T, Shiraishi M, Shigematsu A, Ueta Y: The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes. Anesth Analg. 2004 May;98(5):1401-6, table of contents. [PubMed:15105221 ]
  2. Horishita T, Minami K, Uezono Y, Shiraishi M, Ogata J, Okamoto T, Shigematsu A: The tramadol metabolite, O-desmethyl tramadol, inhibits 5-hydroxytryptamine type 2C receptors expressed in Xenopus Oocytes. Pharmacology. 2006;77(2):93-9. Epub 2006 May 5. [PubMed:16679816 ]
General function:
Involved in ionotropic glutamate receptor activity
Specific function:
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism
Gene Name:
GRIN3A
Uniprot ID:
Q8TCU5
Molecular weight:
125464.1
References
  1. Hara K, Minami K, Sata T: The effects of tramadol and its metabolite on glycine, gamma-aminobutyric acidA, and N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Anesth Analg. 2005 May;100(5):1400-5, table of contents. [PubMed:15845694 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for dynorphins. May play a role in arousal and regulation of autonomic and neuroendocrine functions
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular weight:
42644.7
References
  1. Sun HL, Zheng JW, Wang K, Liu RK, Liang JH: Tramadol reduces the 5-HTP-induced head-twitch response in mice via the activation of mu and kappa opioid receptors. Life Sci. 2003 Jan 31;72(11):1221-30. [PubMed:12570923 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular weight:
66127.4
References
  1. Shiraishi M, Minami K, Uezono Y, Yanagihara N, Shigematsu A: Inhibition by tramadol of muscarinic receptor-induced responses in cultured adrenal medullary cells and in Xenopus laevis oocytes expressing cloned M1 receptors. J Pharmacol Exp Ther. 2001 Oct;299(1):255-60. [PubMed:11561087 ]
  2. Shiga Y, Minami K, Shiraishi M, Uezono Y, Murasaki O, Kaibara M, Shigematsu A: The inhibitory effects of tramadol on muscarinic receptor-induced responses in Xenopus oocytes expressing cloned M(3) receptors. Anesth Analg. 2002 Nov;95(5):1269-73, table of contents. [PubMed:12401609 ]

Transporters

General function:
Involved in neurotransmitter: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
References
  1. Sagata K, Minami K, Yanagihara N, Shiraishi M, Toyohira Y, Ueno S, Shigematsu A: Tramadol inhibits norepinephrine transporter function at desipramine-binding sites in cultured bovine adrenal medullary cells. Anesth Analg. 2002 Apr;94(4):901-6, table of contents. [PubMed:11916794 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  3. Berrocoso E, Mico JA: Cooperative opioid and serotonergic mechanisms generate superior antidepressant-like effects in a mice model of depression. Int J Neuropsychopharmacol. 2009 Sep;12(8):1033-44. doi: 10.1017/S1461145709000236. Epub 2009 Apr 3. [PubMed:19341511 ]
  4. Frink MC, Hennies HH, Englberger W, Haurand M, Wilffert B: Influence of tramadol on neurotransmitter systems of the rat brain. Arzneimittelforschung. 1996 Nov;46(11):1029-36. [PubMed:8955860 ]
General function:
Involved in neurotransmitter: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
References
  1. Barann M, Urban B, Stamer U, Dorner Z, Bonisch H, Bruss M: Effects of tramadol and O-demethyl-tramadol on human 5-HT reuptake carriers and human 5-HT3A receptors: a possible mechanism for tramadol-induced early emesis. Eur J Pharmacol. 2006 Feb 15;531(1-3):54-8. Epub 2006 Jan 19. [PubMed:16427041 ]
  2. Driessen B, Reimann W: Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro. Br J Pharmacol. 1992 Jan;105(1):147-51. [PubMed:1596676 ]
  3. Frink MC, Hennies HH, Englberger W, Haurand M, Wilffert B: Influence of tramadol on neurotransmitter systems of the rat brain. Arzneimittelforschung. 1996 Nov;46(11):1029-36. [PubMed:8955860 ]

Only showing the first 10 proteins. There are 11 proteins in total.