Drugbank Logo

Showing drug card for Tramadol (DB00193)

Legend: drug field target field enzyme field

for drugs
Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:47:31
Primary Accession Number DB00193
Secondary Accession Number
  • APRD00028
Name Tramadol
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description A narcotic analgesic proposed for severe pain. It may be habituating. [PubChem]
Synonyms
  1. Tramadol HCl
  2. Tramadol hydrochloride
  3. Tramadolum [INN-Latin]
  4. Tramodol Hcl
  5. tramadol
Brand Names
  1. Crispin
  2. Ralivia ER
  3. Ralivia Flashtab
  4. Tramadol HCl BP/EP
  5. Tramal
  6. Tridural
  7. Ultram
  8. Zydol
Brand Mixtures Not Available
Chemical IUPAC Name (1R,2R)-2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexan-1-ol
Chemical Formula C16H25NO2
Chemical Structure Structure
CAS Registry Number 27203-92-5
InChI Identifier InChI=1/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 Key TVYLLZQTGLZFBW-ZBFHGGJFBS
KEGG Drug Not Available
KEGG Compound C07153 Link Image
PubChem Compound 33741 Link Image
PubChem Substance 175579 Link Image
ChEBI ID Not Available
PharmGKB ID PA451735 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link http://www.rxlist.com/cgi/generic/tramadol.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Tramadol Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference K. Flick, E. Frankus, U.S. Pat 3,652,589 (1965)
Average Molecular Weight 263.3752
Monoisotopic Molecular Weight 263.1885
State Solid
Melting Point 180-181oC
Experimental Water Solubility Soluble in water. Source: PhysProp
Predicted Water Solubility 7.50e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 2.4 Source: PhysProp
Predicted LogP 2.71 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.55 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 9.41
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES COC1=CC=CC(=C1)[C@@]1(O)CCCC[C@@H]1CN(C)C
Canonical SMILES COC1=CC=CC(=C1)C1(O)CCCCC1CN(C)C
Drug Category
  • Analgesics
  • Analgesics, Opioid
  • Narcotics
ATC Codes
AHFS Codes
  • 28:08.08
Indication Indicated in the treatment of moderate to severe pain.
Pharmacology Tramadol, a centrally-acting analgesic, exists as a racemic mixture of the trans isomer, with important differences in binding, activity, and metabolism associated with the two enantiomers. Although Tramadol is a synthetic analog of codeine, it has a significantly lower affinity for opioid receptors than codeine. Tramadol is used to treat postoperative, dental, cancer, and acute musculosketetal pain and as an adjuvant to NSAID therapy in patients with osteoarthritis.
Mechanism of Action 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 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 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.
Absorption Racemic tramadol is rapidly and almost completely absorbed after oral administration. The mean absolute bioavailability of a 100 mg oral dose is approximately 75%.The mean peak plasma concentration of racemic tramadol and M1 occurs at two and three hours, respectively, after administration in healthy adults.
Toxicity LD50=350mg/kg (orally in mice)
Protein Binding 20%
Biotransformation The major metabolic pathways appear to be N- and O- demethylation and glucuronidation or sulfation in the liver. One metabolite (O-desmethyltramadol, denoted M1) is pharmacologically active in animal models.
Half Life 23 +/- 10 minutes
Dosage Forms
Form Route
Tablet, extended release Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Almotriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Aminoglutethimide Aminoglutethimide may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Amiodarone Amiodarone may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Amiodarone may decrease the effect of Tramadol by decreasing active metabolite production.
Amitriptyline Tramadol increases the risk of serotonin syndrome and seizures.
Amoxapine Tramadol increases the risk of serotonin syndrome and seizures.
Amprenavir Amprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Aprepitant Aprepitant may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Atazanavir Atazanavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Benzphetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Bosentan Bosentan may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Bromocriptine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Cabergoline Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Caffeine Caffeine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Carbamazepine Carbamazepine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Chloroquine Chloroquine may decrease the effect of Tramadol by decreasing active metabolite production.
Chlorpromazine Chlorpromazine may decrease the effect of Tramadol by decreasing active metabolite production.
Cimetidine Cimetidine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Cimetidine may decrease the effect of Tramadol by decreasing active metabolite production.
Cinacalcet Cinacalcet may decrease the effect of Tramadol by decreasing active metabolite production.
Citalopram Tramadol increases the risk of serotonin syndrome and seizures.
Clarithromycin Clarithromycin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Clomipramine Tramadol increases the risk of serotonin syndrome and seizures. Clomipramine may decrease the effect of Tramadol by decreasing active metabolite production.
Clotrimazole Clotrimazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Clozapine Clozapine may decrease the effect of Tramadol by decreasing active metabolite production.
Cocaine Cocaine may decrease the effect of Tramadol by decreasing active metabolite production.
Conivaptan Conivaptan may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Cyclobenzaprine Increases risk of seizure.
Cyclosporine Cyclosporine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Darifenacin Darifenacin may decrease the effect of Tramadol by decreasing active metabolite production.
Darunavir Darunavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Delavirdine Delavirdine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Delavirdine may decrease the effect of Tramadol by decreasing active metabolite production.
Desipramine Tramadol increases the risk of serotonin syndrome and seizures. Desipramine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Desipramine may decrease the effect of Tramadol by decreasing active metabolite production.
Dexamethasone Dexamethasone may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Dextroamphetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dextromethorphan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dihydroergotamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Diltiazem Diltiazem may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Diphenhydramine Diphenhydramine may decrease the effect of Tramadol by decreasing active metabolite production.
Doxepin Tramadol increases the risk of serotonin syndrome and seizures.
Doxycycline Doxycycline may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Duloxetine Duloxetine may decrease the effect of Tramadol by decreasing active metabolite production. Increased risk of serotonin syndrome. Monitor for Tramadol efficacy and symptoms of serotonin syndrome.
Efavirenz Efavirenz may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Eletriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ergoloid mesylate Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ergonovine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ergotamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Erythromycin Erythromycin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Escitalopram Tramadol increases the risk of serotonin syndrome and seizures.
Etravirine Etravirine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Fluconazole Fluconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Fluoxetine Tramadol increases the risk of serotonin syndrome and seizures. Fluoxetine may decrease the effect of Tramadol by decreasing active metabolite production.
Fluvoxamine Tramadol increases the risk of serotonin syndrome and seizures.
Fosamprenavir Fosamprenavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Fosphenytoin Fosphenytoin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Frovatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Furazolidone Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Furazolidone.
Haloperidol Haloperidol may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Haloperidol may decrease the effect of Tramadol by decreasing active metabolite production.
Imatinib Imatinib may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Imatinib may decrease the effect of Tramadol by decreasing active metabolite production.
Imipramine Tramadol increases the risk of serotonin syndrome and seizures. Imipramine may decrease the effect of Tramadol by decreasing active metabolite production.
Indinavir Indinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Isocarboxazid Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Isocarboxazid.
Isoniazid Isoniazid may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Isoniazid may decrease the effect of Tramadol by decreasing active metabolite production.
Itraconazole Itraconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Ketoconazole Ketoconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Ketoconazole may decrease the effect of Tramadol by decreasing active metabolite production.
Lapatinib Lapatinib may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Lidocaine Lidocaine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Lidocaine may decrease the effect of Tramadol by decreasing active metabolite production.
Linezolid Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Linezolid.
Lisdexamfetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Lopinavir Lopinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Lopinavir may decrease the effect of Tramadol by decreasing active metabolite production.
Maprotiline Increased risk of serotonin syndrome. The 2D6 inhibitor, Trazodone, may also increase the efficacy of Maprotiline by decreasing Maprotiline metabolism and clearance. Monitor for symptoms of serotonin syndrome and changes in Maprotiline efficacy if Trazodone is initiated, discontinued or dose changed.
Meperidine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Methadone Methadone may decrease the effect of Tramadol by decreasing active metabolite production.
Methamphetamine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Methylergonovine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Metronidazole Metronidazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Miconazole Miconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Miconazole may decrease the effect of Tramadol by decreasing active metabolite production.
Mirtazapine Increased risk of serotonin syndrome. The 2D6 inhibitor, Trazodone, may also increase the efficacy of Mirtazapine by decreasing Mirtazapine metabolism and clearance. Monitor for symptoms of serotonin syndrome and changes in Mirtazapine efficacy if Trazodone is initiated, discontinued or dose changed.
Moclobemide Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Moclobemide.
Nafcillin Nafcillin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Naratriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Nefazodone Nefazodone may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Increased risk of serotonin syndrome. Monitor for Tramadol toxicity and symptoms of serotonin syndrome.
Nelfinavir Nelfinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Nevirapine Nevirapine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Nicardipine Nicardipine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Nicardipine may decrease the effect of Tramadol by decreasing active metabolite production.
Nilotinib Nilotinib may decrease the effect of Tramadol by decreasing active metabolite production.
Norfloxacin Norfloxacin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Nortriptyline Tramadol increases the risk of serotonin syndrome and seizures.
Oxcarbazepine Oxcarbazepine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Paroxetine Tramadol increases the risk of serotonin syndrome and seizures. Paroxetine may decrease the effect of Tramadol by decreasing active metabolite production.
Pentobarbital Pentobarbital may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Pergolide Pergolide may decrease the effect of Tramadol by decreasing active metabolite production. Increased risk of serotonin syndrome. Monitor for Tramadol efficacy and symptoms of serotonin syndrome.
Phendimetrazine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Phenelzine Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Phenelzine.
Phenobarbital Phenobarbital may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Phentermine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Phenytoin Phenytoin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Pioglitazone Pioglitazone may decrease the effect of Tramadol by decreasing active metabolite production.
Posaconazole Posaconazole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Primidone Primidone may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Procarbazine Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Procarbazine.
Promethazine Increased risk of serotonin syndrome. Increased risk of seizures. Monitor for symptoms of serotonin syndrome.
Protriptyline Tramadol increases the risk of serotonin syndrome and seizures.
Pyrimethamine Pyrimethamine may decrease the effect of Tramadol by decreasing active metabolite production.
Quinidine Quinidine may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Quinidine may decrease the effect of Tramadol by decreasing active metabolite production.
Quinine Quinine may decrease the effect of Tramadol by decreasing active metabolite production.
Ranolazine Ranolazine may decrease the effect of Tramadol by decreasing active metabolite production.
Rasagiline Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Rasagiline.
Rifabutin Rifabutin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Rifampin Rifampin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Rifapentine Rifapentine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Ritonavir Ritonavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Ritonavir may decrease the effect of Tramadol by decreasing active metabolite production.
Rizatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
S-Adenosylmethionine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Saquinavir Saquinavir may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Selegiline Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Selegiline.
Sertraline Tramadol increases the risk of serotonin syndrome and seizures. Sertraline may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Sertraline may decrease the effect of Tramadol by decreasing active metabolite production.
Sibutramine Sibutramine may incrase the serotonergic effect of the Tramadol. Concomitant therapy should be avoided.
St. John's Wort St. John's Wort may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.
Sumatriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Telithromycin Telithromycin may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Terbinafine Terbinafine may decrease the effect of Tramadol by decreasing active metabolite production.
Tetracycline Tetracycline may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Thioridazine Thioridazine may decrease the effect of Tramadol by decreasing active metabolite production.
Ticlopidine Ticlopidine may decrease the effect of Tramadol by decreasing active metabolite production.
Tranylcypromine Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Tranylcypromine. Tranylcypromine may decrease the effect of Tramadol by decreasing active metabolite production.
Trazodone Trazodone may decrease the effect of Tramadol by decreasing active metabolite production. Increased risk of serotonin syndrome. Monitor for Tramadol efficacy and symptoms of serotonin syndrome.
Trimipramine Tramadol increases the risk of serotonin syndrome and seizures.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Verapamil Verapamil may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Voriconazole Voriconzole may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Zolmitriptan Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
sitaxentan Sitaxsentan may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
Food Interactions Not Available
Pathways Not Available
General References
  1. 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 Link Image]
  2. 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 Link Image]
  3. Dayer P, Desmeules J, Collart L: [Pharmacology of tramadol] Drugs. 1997;53 Suppl 2:18-24. [PubMed Link Image]
  4. 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 Link Image]
  5. 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 Link Image]
  6. Drugs.com Link Image
  7. Wikipedia Link Image
  8. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2D6 (CYP2D6)
Targets
  1. Sodium-dependent noradrenaline transporter
  2. 5-hydroxytryptamine 2C receptor
  3. Kappa-type opioid receptor
  4. Sodium-dependent serotonin transporter
  5. Mu-type opioid receptor
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2D6 (CYP2D6)
Enzyme 1 Gene Name CYP2D6
Enzyme 1 SwissProt ID P10635 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P10635|CP2D6_HUMAN Cytochrome P450 2D6 (EC 1.14.14.1) 
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGMTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
Drug Target 1 [top]
Target 1 ID 540
Target 1 Name Sodium-dependent noradrenaline transporter
Target 1 Synonyms
  1. NET
  2. Norepinephrine transporter
Target 1 Gene Name SLC6A2
Target 1 Protein Sequence >Sodium-dependent noradrenaline transporter 
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWG
KKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYN
REGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTW
NSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLC
LMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFY
RLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFA
IFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSS
MGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTS
ILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINF
KPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHL
VAQRDIRQFQLQHWLAI
Target 1 Number of Residues 627
Target 1 Molecular Weight 69333
Target 1 Theoretical pI 7.53
Target 1 GO Classification
Function
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity
Process
physiological process
cellular physiological process
transport
neurotransmitter transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane
Target 1 General Function Involved in neurotransmitter:sodium symporter activity
Target 1 Specific Function Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 65-85
  • 93-112
  • 136-156
  • 235-253
  • 262-279
  • 315-332
  • 344-365
  • 398-417
  • 444-462
  • 478-498
  • 519-538
  • 557-575
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 189258 Link Image
Target 1 UniProtKB/Swiss-Prot ID P23975 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name SC6A2_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1854 bp 
ATGCTTCTGGCGCGGATGAACCCGCAGGTGCAGCCCGAGAACAACGGGGCGGACACGGGT
CCAGAGCAGCCCCTTCGGGCGCGCAAAACTGCGGAGCTGCTGGTGGTGAAGGAGCGCAAC
GGCGTCCAGTGCCTGCTGGCGCCCCGCGACGGCGACGCGCAGCCCCGGGAGACCTGGGGC
AAGAAGATCGACTTCCTGCTGTCCGTAGTCGGCTTCGCAGTGGACCTGGCCAACGTGTGG
CGCTTCCCCTACCTCTGCTACAAGAACGGCGGCGGTGCCTTCTTGATCCCGTACACACTG
TTCCTTATCATCGCGGGGATGCCCCTGTTCTACATGGAGCTGGCTCTGGGACAGTACAAC
CGGGAGGGGGCTGCCACCGTTTGGAAAATCTGCCCATTCTTCAAAGGCGTTGGCTATGCT
GTCATCCTGATCGCCCTGTACGTTGGCTTCTACTACAACGTCATCATCGCCTGGTCACTC
TACTACCTCTTCTCCTCCTTCACCCTCAACCTGCCCTGGACCGACTGTGGCCACACCTGG
AACAGCCCCAACTGTACCGACCCCAAGCTCCTCAATGGCTCCGTGCTTGGCAACCACACC
AAGTACTCCAAGTACAAGTTCACGCCGGCAGCCGAGTTTTATGAGCGTGGTGTCCTGCAC
CTTCACGAGAGCAGCGGGATTCATGACATCGGCCTGCCCCAGTGGCAGCTCTTGCTCTGT
CTGATGGTCGTCGTCATCGTCTTGTATTTTAGCCTCTGGAAAGGGGTGAAGACATCAGGA
AAGGTGGTGTGGATCACAGCCACGCTGCCTTACTTCGTGCTGTTCGTGCTCCTGGTCCAT
GGCGTCACGCTGCCCGGAGCCTCCAATGGCATCAATGCCTACCTGCACATCGACTTCTAC
CGCTTGAAAGAGGCCACGGTATGGATTGATGCCGCAACTCAGATATTTTTTTCCTTGGGG
GCTGGATTTGGAGTATTGATTGCATTTGCCAGTTACAACAAATTTGACAACAACTGTTAC
AGGGATGCCCTGCTGACCAGCAGCATCAACTGTATCACCAGCTTCGTCTCTGGGTTCGCC
ATCTTCTCCATCCTTGGTTACATGGCCCATGAACACAAGGTCAACATTGAGGATGTGGCC
ACAGAAGGAGCTGGCCTAGTGTTCATCCTGTATCCAGAGGCCATTTCTACCCTGTCTGGA
TCTACATTCTGGGCTGTTGTGTTTTTCGTCATGCTCCTGGCGCTGGGCCTTGACAGCTCA
ATGGGAGGCATGGAGGCTGTCATCACGGGCCTGGCAGATGACTTCCAGGTCCTGAAGCGA
CACCGGAAACTCTTCACATTTGGCGTCACCTTCAGCACTTTCCTTCTCGCCCTGTTCTGC
ATAACCAAGGGTGGAATTTACGTCTTGACCCTCCTGGACACCTTTGCTGCGGGCACCTCC
ATCCTTTTTGCTGTCCTCATGGAAGCCATCGGAGTTTCCTGGTTTTATGGAGTGGACAGG
TTCAGCAACGACATCCAGCAGATGATGGGGTTCAGGCCGGGTCTATACTGGAGACTGTGC
TGGAAGTTCGTCAGTCCTGCCTTCCTCCTGTTCGTGGTTGTGGTCAGCATCATCAACTTC
AAGCCACTCACCTACGACGACTACATCTTCCCGCCCTGGGCCAACTGGGTGGGGTGGGGC
ATCGCCCTGTCCTCCATGGTCCTGGTGCCCATCTACGTCATCTATAAGTTCCTCAGCACG
CAGGGCTCTCTTTGGGAGAGACTGGCCTATGGCATCACGCCAGAGAACGAGCACCACCTG
GTGGCTCAGAGGGACATCAGACAGTTCCAGTTGCAACACTGGCTGGCCATCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID SLC6A2 Link Image
Target 1 GenAtlas ID SLC6A2 Link Image
Target 1 HGNC ID HGNC:11048 Link Image
Target 1 Chromosome Location 16
Target 1 Locus 16q12.2
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Shannon JR, Flattem NL, Jordan J, Jacob G, Black BK, Biaggioni I, Blakely RD, Robertson D: Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N Engl J Med. 2000 Feb 24;342(8):541-9. [PubMed Link Image]
  2. Torres GE, Yao WD, Mohn AR, Quan H, Kim KM, Levey AI, Staudinger J, Caron MG: Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron. 2001 Apr;30(1):121-34. [PubMed Link Image]
  3. Pacholczyk T, Blakely RD, Amara SG: Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. Nature. 1991 Mar 28;350(6316):350-4. [PubMed Link Image]
  4. Porzgen P, Bonisch H, Bruss M: Molecular cloning and organization of the coding region of the human norepinephrine transporter gene. Biochem Biophys Res Commun. 1995 Oct 24;215(3):1145-50. [PubMed Link Image]
Target 1 Drug References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  2. 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 Link Image]
Drug Target 2 [top]
Target 2 ID 590
Target 2 Name 5-hydroxytryptamine 2C receptor
Target 2 Synonyms
  1. 5- HT2C
  2. 5-HT-2C
  3. 5-HTR2C
  4. 5HT-1C
  5. Serotonin receptor 2C
Target 2 Gene Name HTR2C
Target 2 Protein Sequence >5-hydroxytryptamine 2C receptor 
MVNLRNAVHSFLVHLIGLLVWQCDISVSPVAAIVTDIFNTSDGGRFKFPDGVQNWPALSI
VIIIIMTIGGNILVIMAVSMEKKLHNATNYFLMSLAIADMLVGLLVMPLSLLAILYDYVW
PLPRYLCPVWISLDVLFSTASIMHLCAISLDRYVAIRNPIEHSRFNSRTKAIMKIAIVWA
ISIGVSVPIPVIGLRDEEKVFVNNTTCVLNDPNFVLIGSFVAFFIPLTIMVITYCLTIYV
LRRQALMLLHGHTEEPPGLSLDFLKCCKRNTAEEENSANPNQDQNARRRKKKERRPRGTM
QAINNERKASKVLGIVFFVFLIMWCPFFITNILSVLCEKSCNQKLMEKLLNVFVWIGYVC
SGINPLVYTLFNKIYRRAFSNYLRCNYKVEKKPPVRQIPRVAATALSGRELNVNIYRHTN
EPVIEKASDNEPGIEMQVENLELPVNPSSVVSERISSV
Target 2 Number of Residues 465
Target 2 Molecular Weight 51822
Target 2 Theoretical pI 9.11
Target 2 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in rhodopsin-like receptor activity
Target 2 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
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 53-78
  • 90-110
  • 128-150
  • 171-193
  • 214-235
  • 312-333
  • 349-371
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 338028 Link Image
Target 2 UniProtKB/Swiss-Prot ID P28335 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name 5HT2C_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >1377 bp 
ATGGTGAACCTGAGGAATGCGGTGCATTCATTCCTTGTGCACCTAATTGGCCTATTGGTT
TGGCAATGTGATATTTCTGTGAGCCCAGTAGCAGCTATAGTAACTGACATTTTCAATACC
TCCGATGGTGGACGCTTCAAATTCCCAGACGGGGTACAAAACTGGCCAGCACTTTCAATC
GTCATCATAATAATCATGACAATAGGTGGCAACATCCTTGTGATCATGGCAGTAAGCATG
GAAAAGAAACTGCACAATGCCACCAATTACTTCTTAATGTCCCTAGCCATTGCTGATATG
CTAGTGGGACTACTTGTCATGCCCCTGTCTCTCCTGGCAATCCTTTATGATTATGTCTGG
CCACTACCTAGATATTTGTGCCCCGTCTGGATTTCTTTAGATGTTTTATTTTCAACAGCG
TCCATCATGCACCTCTGCGCTATATCGCTGGATCGGTATGTAGCAATACGTAATCCTATT
GAGCATAGCCGTTTCAATTCGCGGACTAAGGCCATCATGAAGATTGCTATTGTTTGGGCA
ATTTCTATAGGTGTATCAGTTCCTATCCCTGTGATTGGACTGAGGGACGAAGAAAAGGTG
TTCGTGAACAACACGACGTGCGTGCTCAACGACCCAAATTTCGTTCTTATTGGGTCCTTC
GTAGCTTTCTTCATACCGCTGACGATTATGGTGATTACGTATTGCCTGACCATCTACGTT
CTGCGCCGACAAGCTTTGATGTTACTGCACGGCCACACCGAGGAACCGCCTGGACTAAGT
CTGGATTTCCTGAAGTGCTGCAAGAGGAATACGGCCGAGGAAGAGAACTCTGCAAACCCT
AACCAAGACCAGAACGCACGCCGAAGAAAGAAGAAGGAGAGACGTCCTAGGGGCACCATG
CAGGCTATCAACAATGAAAGAAAAGCTTCGAAAGTCCTTGGGATTGTTTTCTTTGTGTTT
CTGATCATGTGGTGCCCATTTTTCATTACCAATATTCTGTCTGTTCTTTGTGAGAAGTCC
TGTAACCAAAAGCTCATGGAAAAGCTTCTGAATGTGTTTGTTTGGATTGGCTATGTTTGT
TCAGGAATCAATCCTCTGGTGTATACTCTGTTCAACAAAATTTACCGAAGGGCATTCTCC
AACTATTTGCGTTGCAATTATAAGGTAGAGAAAAAGCCTCCTGTCAGGCAGATTCCAAGA
GTTGCCGCCACTGCTTTGTCTGGGAGGGAGCTTAATGTTAACATTTATCGGCATACCAAT
GAACCGGTGATCGAGAAAGCCAGTGACAATGAGCCCGGTATAGAGATGCAAGTTGAGAAT
TTAGAGTTACCAGTAAATCCCTCCAGTGTGGTTAGCGAAAGGATTAGCAGTGTGTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID HTR2C Link Image
Target 2 GenAtlas ID HTR2C Link Image
Target 2 HGNC ID HGNC:5295 Link Image
Target 2 Chromosome Location X
Target 2 Locus Xq24
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Samochowiec J, Smolka M, Winterer G, Rommelspacher H, Schmidt LG, Sander T: Association analysis between a Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene and neuronal hyperexcitability. Am J Med Genet. 1999 Apr 16;88(2):126-30. [PubMed Link Image]
  2. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  3. Marshall SE, Bird TG, Hart K, Welsh KI: Unified approach to the analysis of genetic variation in serotonergic pathways. Am J Med Genet. 1999 Dec 15;88(6):621-7. [PubMed Link Image]
  4. Becamel C, Figge A, Poliak S, Dumuis A, Peles E, Bockaert J, Lubbert H, Ullmer C: Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1. J Biol Chem. 2001 Apr 20;276(16):12974-82. Epub 2001 Jan 9. [PubMed Link Image]
  5. Saltzman AG, Morse B, Whitman MM, Ivanshchenko Y, Jaye M, Felder S: Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1469-78. [PubMed Link Image]
  6. Lappalainen J, Zhang L, Dean M, Oz M, Ozaki N, Yu DH, Virkkunen M, Weight F, Linnoila M, Goldman D: Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C). Genomics. 1995 May 20;27(2):274-9. [PubMed Link Image]
  7. Stam NJ, Vanderheyden P, van Alebeek C, Klomp J, de Boer T, van Delft AM, Olijve W: Genomic organisation and functional expression of the gene encoding the human serotonin 5-HT2C receptor. Eur J Pharmacol. 1994 Nov 15;269(3):339-48. [PubMed Link Image]
  8. Xie E, Zhu L, Zhao L, Chang LS: The human serotonin 5-HT2C receptor: complete cDNA, genomic structure, and alternatively spliced variant. Genomics. 1996 Aug 1;35(3):551-61. [PubMed Link Image]
  9. Niswender CM, Sanders-Bush E, Emeson RB: Identification and characterization of RNA editing events within the 5-HT2C receptor. Ann N Y Acad Sci. 1998 Dec 15;861:38-48. [PubMed Link Image]
Target 2 Drug 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 Link Image]
  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 Link Image]
Drug Target 3 [top]
Target 3 ID 696
Target 3 Name Kappa-type opioid receptor
Target 3 Synonyms
  1. KOR-1
Target 3 Gene Name OPRK1
Target 3 Protein Sequence >Kappa-type opioid receptor 
MDSPIQIFRGEPGPTCAPSACLPPNSSAWFPGWAEPDSNGSAGSEDAQLEPAHISPAIPV
IITAVYSVVFVVGLVGNSLVMFVIIRYTKMKTATNIYIFNLALADALVTTTMPFQSTVYL
MNSWPFGDVLCKIVISIDYYNMFTSIFTLTMMSVDRYIAVCHPVKALDFRTPLKAKIINI
CIWLLSSSVGISAIVLGGTKVREDVDVIECSLQFPDDDYSWWDLFMKICVFIFAFVIPVL
IIIVCYTLMILRLKSVRLLSGSREKDRNLRRITRLVLVVVAVFVVCWTPIHIFILVEALG
STSHSTAALSSYYFCIALGYTNSSLNPILYAFLDENFKRCFRDFCFPLKMRMERQSTSRV
RNTVQDPAYLRDIDGMNKPV
Target 3 Number of Residues 386
Target 3 Molecular Weight 42646
Target 3 Theoretical pI 7.79
Target 3 GO Classification
Function
peptide receptor activity, G-protein coupled
opioid receptor activity
kappa-opioid receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 3 General Function Involved in rhodopsin-like receptor activity
Target 3 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
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 59-85
  • 96-117
  • 133-154
  • 174-196
  • 223-247
  • 276-299
  • 312-333
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 532060 Link Image
Target 3 UniProtKB/Swiss-Prot ID P41145 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name OPRK_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 3 Gene Sequence >1143 bp 
ATGGAATCCCCGATTCAGATCTTCCGCGGGGAGCCTGGCCCTACCTGCGCCCCGAGCGCC
TGCCTGCCCCCCAACAGCAGCGCCTGGTTTCCCGGCTGGGCCGAGCCCGACAGCAACGGC
AGCGCCGGCTCGGAGGACGCGCAGCTGGAGCCCGCGCACATCTCCCCGGCCATCCCGGTC
ATCATCACGGCGGTCTACTCCGTAGTGTTCGTCGTGGGCTTGGTGGGCAACTCGCTGGTC
ATGTTCGTGATCATCCGATACACAAAGATGAAGACAGCAACCAACATTTACATATTTAAC
CTGGCTTTGGCAGATGCTTTAGTTACTACAACCATGCCCTTTCAGAGTACGGTCTACTTG
ATGAATTCCTGGCCTTTTGGGGATGTGCTGTGCAAGATAGTAATTTCCATTGATTACTAC
AACATGTTCACCAGCATCTTCACCTTGACCATGATGAGCGTGGACCGCTACATTGCCGTG
TGCCACCCCGTGAAGGCTTTGGACTTCCGCACACCCTTGAAGGCAAAGATCATCAATATC
TGCATCTGGCTGCTGTCGTCATCTGTTGGCATCTCTGCAATAGTCCTTGGAGGCACCAAA
GTCAGGGAAGACGTCGATGTCATTGAGTGCTCCTTGCAGTTCCCAGATGATGACTACTCC
TGGTGGGACCTCTTCATGAAGATCTGCGTCTTCATCTTTGCCTTCGTGATCCCTGTCCTC
ATCATCATCGTCTGCTACACCCTGATGATCCTGCGTCTCAAGAGCGTCCGGCTCCTTTCT
GGCTCCCGAGAGAAAGATCGCAACCTGCGTAGGATCACCAGACTGGTCCTGGTGGTGGTG
GCGGTTTTCGTCGTCTGCTGGACTCCCATTCACATATTCATCCTGGTGGAGGCTCTGGGG
AGCACCTCCCACAGCACAGCTGCTCTCTCCAGCTATTACTTCTGCATCGCCTTAGGCTAT
ACCAACAGTAGCCTGAATCCCATTCTCTACGCCTTTCTTGATGAAAACTTCAAGCGGTGT
TTCCGGGACTTCTGCTTTCCACTGAAGATGAGGATGGAGCGGCAGAGCACTAGCAGAGTC
CGAAATACAGTTCAGGATCCTGCTTACCTGAGGGACATCGATGGGATGAATAAACCAGTA
TGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID OPRK1 Link Image
Target 3 GenAtlas ID OPRK1 Link Image
Target 3 HGNC ID HGNC:8154 Link Image
Target 3 Chromosome Location 8
Target 3 Locus 8q11.2
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Li JG, Chen C, Liu-Chen LY: Ezrin-radixin-moesin-binding phosphoprotein-50/Na+/H+ exchanger regulatory factor (EBP50/NHERF) blocks U50,488H-induced down-regulation of the human kappa opioid receptor by enhancing its recycling rate. J Biol Chem. 2002 Jul 26;277(30):27545-52. Epub 2002 May 9. [PubMed Link Image]
  2. Simonin F, Gaveriaux-Ruff C, Befort K, Matthes H, Lannes B, Micheletti G, Mattei MG, Charron G, Bloch B, Kieffer B: kappa-Opioid receptor in humans: cDNA and genomic cloning, chromosomal assignment, functional expression, pharmacology, and expression pattern in the central nervous system. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7006-10. [PubMed Link Image]
  3. Zhu J, Chen C, Xue JC, Kunapuli S, DeRiel JK, Liu-Chen LY: Cloning of a human kappa opioid receptor from the brain. Life Sci. 1995;56(9):PL201-7. [PubMed Link Image]
  4. Wang JB, Johnson PS, Wu JM, Wang WF, Uhl GR: Human kappa opiate receptor second extracellular loop elevates dynorphin's affinity for human mu/kappa chimeras. J Biol Chem. 1994 Oct 21;269(42):25966-9. [PubMed Link Image]
  5. Mansson E, Bare L, Yang D: Isolation of a human kappa opioid receptor cDNA from placenta. Biochem Biophys Res Commun. 1994 Aug 15;202(3):1431-7. [PubMed Link Image]
Target 3 Drug 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 Link Image]
Drug Target 4 [top]
Target 4 ID 824
Target 4 Name Sodium-dependent serotonin transporter
Target 4 Synonyms
  1. 5HT transporter
  2. 5HTT
Target 4 Gene Name SLC6A4
Target 4 Protein Sequence >Sodium-dependent serotonin transporter 
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR
HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP
YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM
AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH
RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA
TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD
ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS
TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT
LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC
WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT
PGTFKERIIKSITPETPTEIPCGDIRLNAV
Target 4 Number of Residues 640
Target 4 Molecular Weight 70325
Target 4 Theoretical pI 6.17
Target 4 GO Classification
Function
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity
Process
physiological process
cellular physiological process
transport
neurotransmitter transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane
Target 4 General Function Involved in serotonin:sodium symporter activity
Target 4 Specific Function Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • 88-108
  • 116-135
  • 160-180
  • 253-271
  • 280-297
  • 333-350
  • 362-383
  • 417-436
  • 464-482
  • 498-518
  • 539-558
  • 577-595
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 36433 Link Image
Target 4 UniProtKB/Swiss-Prot ID P31645 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name SC6A4_HUMAN Link Image
Target 4 PDB ID Not Available
Target 4 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 4 Gene Sequence >1893 bp 
ATGGAGACGACGCCCTTGAATTCTCAGAAGCAGCTATCAGCGTGTGAAGATGGAGAAGAT
TGTCAGGAAAACGGAGTTCTACAGAAGGTTGTTCCCACCCCAGGGGACAAAGTGGAGTCC
GGGCAAATATCCAATGGGTACTCAGCAGTTCCAAGTCCTGGTGCGGGAGATGACACACGG
CACTCTATCCCAGCGACCACCACCACCCTAGTGGCTGAGCTTCATCAAGGGGAACGGGAG
ACCTGGGGCAAGAAGGTGGATTTCCTTCTCTCAGTGATTGGCTATGCTGTGGACCTGGGC
AATGTCTGGCGCTTCCCCTACATATGTTACCAGAATGGAGGGGGGGCATTCCTCCTCCCC
TACACCATCATGGCCATTTTTGGGGGAATCCCGCTCTTTTACATGGAGCTCGCACTGGGA
CAGTACCACCGAAATGGATGCATTTCAATATGGAGGAAAATCTGCCCGATTTTCAAAGGG
ATTGGTTATGCCATCTGCATCATTGCCTTTTACATTGCTTCCTACTACAACACCATCATG
GCCTGGGCGCTATACTACCTCATCTCCTCCTTCACGGACCAGCTGCCCTGGACCAGCTGC
AAGAACTCCTGGAACACTGGCAACTGCACCAATTACTTCTCCGAGGACAACATCACCTGG
ACCCTCCATTCCACGTCCCCTGCTGAAGAATTTTACACGCGCCACGTCCTGCAGATCCAC
CGGTCTAAGGGGCTCCAGGACCTGGGGGGCATCAGCTGGCAGCTGGCCCTCTGCATCATG
CTGATCTTCACTGTTATCTACTTCAGCATCTGGAAAGGCGTCAAGACCTCTGGCAAGGTG
GTGTGGGTGACAGCCACCTTCCCTTATATCATCCTTTCTGTCCTGCTGGTGAGGGGTGCC
ACCCTCCCTGGAGCCTGGAGGGGTGTTCTCTTCTACTTGAAACCCAATTGGCAGAAACTC
CTGGAGACAGGGGTGTGGATAGATGCAGCCGCTCAGATCTTCTTCTCTCTTGGTCCGGGC
TTTGGGGTCCTGCTGGCTTTTGCTAGCTACAACAAGTTCAACAACAACTGCTACCAAGAT
GCCCTGGTGACCAGCGTGGTGAACTGCATGACGAGCTTCGTTTCGGGATTTGTCATCTTC
ACAGTGCTCGGTTACATGGCTGAGATGAGGAATGAAGATGTGTCTGAGGTGGCCAAAGAC
GCAGGTCCCAGCCTCCTCTTCATCACGTATGCAGAAGCGATAGCCAACATGCCAGCGTCC
ACTTTCTTTGCCATCATCTTCTTTCTGATGTTAATCACGCTGGGCTTGGACAGCACGTTT
GCAGGCTTGGAGGGGGTGATCACGGCTGTGCTGGATGAGTTCCCACACGTCTGGGCCAAG
CGCCGGGAGCGGTTCGTGCTCGCCGTGGTCATCACCTGCTTCTTTGGATCCCTGGTCACC
CTGACTTTTGGAGGGGCCTACGTGGTGAAGCTGCTGGAGGAGTATGCCACGGGGCCCGCA
GTGCTCACTGTCGCGCTGATCGAAGCAGTCGCTGTGTCTTGGTTCTATGGCATCACTCAG
TTCTGCAGGGACGTGAAGGAAATGCTCGGCTTCAGCCCGGGGTGGTTCTGGAGGATCTGC
TGGGTGGCCATCAGCCCTCTGTTTCTCCTGTTCATCATTTGCAGTTTTCTGATGAGCCCG
CCACAACTACGACTTTTCCAATATAATTATCCTTACTGGAGTATCATCTTGGGTTACTGC
ATAGGAACCTCATCTTTCATTTGCATCCCCACATATATAGCTTATCGGTTGATCATCACT
CCAGGGACATTTAAAGAGCGTATTATTAAAAGTATTACCCCGGAGACACCAACAGAAATT
CCTTGTGGGGACATCCGCTTGAATGCTGTGTAA
Target 4 GenBank Gene ID
Target 4 GeneCard ID SLC6A4 Link Image
Target 4 GenAtlas ID SLC6A4 Link Image
Target 4 HGNC ID HGNC:11050 Link Image
Target 4 Chromosome Location 17
Target 4 Locus 17q11.1-q12
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R: Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003 Jul 18;301(5631):386-9. [PubMed Link Image]
  3. Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS, Ganapathy V, Blakely RD: Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2542-6. [PubMed Link Image]
  4. Lesch KP, Wolozin BL, Murphy DL, Reiderer P: Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem. 1993 Jun;60(6):2319-22. [PubMed Link Image]
  5. Lesch KP, Wolozin BL, Estler HC, Murphy DL, Riederer P: Isolation of a cDNA encoding the human brain serotonin transporter. J Neural Transm Gen Sect. 1993;91(1):67-72. [PubMed Link Image]
Target 4 Drug References
  1. 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 Link Image]
  2. 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 Link Image]
Drug Target 5 [top]
Target 5 ID 847
Target 5 Name Mu-type opioid receptor
Target 5 Synonyms
  1. MOR-1
Target 5 Gene Name OPRM1
Target 5 Protein Sequence >Mu-type opioid receptor 
MDSSAAPTNASNCTDALAYSSCSPAPSPGSWVNLSHLDGNLSDPCGPNRTDLGGRDSLCP
PTGSPSMITAITIMALYSIVCVVGLFGNFLVMYVIVRYTKMKTATNIYIFNLALADALAT
STLPFQSVNYLMGTWPFGTILCKIVISIDYYNMFTSIFTLCTMSVDRYIAVCHPVKALDF
RTPRNAKIINVCNWILSSAIGLPVMFMATTKYRQGSIDCTLTFSHPTWYWENLLKICVFI
FAFIMPVLIITVCYGLMILRLKSVRMLSGSKEKDRNLRRITRMVLVVVAVFIVCWTPIHI
YVIIKALVTIPETTFQTVSWHFCIALGYTNSCLNPVLYAFLDENFKRCFREFCIPTSSNI
EQQNSTRIRQNTRDHPSTANTVDRTNHQLENLEAETAPLP
Target 5 Number of Residues 406
Target 5 Molecular Weight 44780
Target 5 Theoretical pI 8.29
Target 5 GO Classification
Function
peptide receptor activity, G-protein coupled
opioid receptor activity
mu-opioid receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 5 General Function Involved in rhodopsin-like receptor activity
Target 5 Specific Function Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin
Target 5 Pathways Not Available
Target 5 Reactions Not Available
Target 5 Pfam Domain Function
Target 5 Signals
  • None
Target 5 Transmembrane Regions
  • 67-96
  • 106-123
  • 146-165
  • 196-211
  • 237-259
  • 283-305
  • 314-330
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 452073 Link Image
Target 5 UniProtKB/Swiss-Prot ID P35372 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name OPRM_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 5 Gene Sequence >1203 bp 
ATGGACAGCAGCGCTGCCCCCACGAACGCCAGCAATTGCACTGATGCCTTGGCGTACTCA
AGTTGCTCCCCAGCACCCAGCCCCGGTTCCTGGGTCAACTTGTCCCACTTAGATGGCAAC
CTGTCCGACCCATGCGGTCCGAACCGCACCAACCTGGGCGGGAGAGACAGCCTGTGCCCT
CCGACCGGCAGTCCCTCCATGATCACGGCCATCACGATCATGGCCCTCTACTCCATCGTG
TGCGTGGTGGGGCTCTTCGGAAACTTCCTGGTCATGTATGTGATTGTCAGATACACCAAG
ATGAAGACTGCCACCAACATCTACATTTTCAACCTTGCTCTGGCAGATGCCTTAGCCACC
AGTACCCTGCCCTTCCAGAGTGTGAATTACCTAATGGGAACATGGCCATTTGGAACCATC
CTTTGCAAGATAGTGATCTCCATAGATTACTATAACATGTTCACCAGCATATTCACCCTC
TGCACCATGAGTGTTGATCGATACATTGCAGTCTGCCACCCTGTCAAGGCCTTAGATTTC
CGTACTCCCCGAAATGCCAAAATTATCAATGTCTGCAACTGGATCCTCTCTTCAGCCATT
GGTCTTCCTGTAATGTTCATGGCTACAACAAAATACAGGCAAGGTTCCATAGATTGTACA
CTAACATTCTCTCATCCAACCTGGTACTGGGAAAACCTCGTGAAGATCTGTGTTTTCATC
TTCGCCTTCATTATGCCAGTGCTCATCATTACCGTGTGCTATGGACTGATGATCTTGCGC
CTCAAGAGTGTCCGCATGCTCTCTGGCTCCAAAGAAAAGGACAGGAATCTTCGAAGGATC
ACCAGGATGGTGCTGGTGGTGGTGGCTGTGTTCATCGTCTGCTGGACTCCCATTCACATT
TACGTCATCATTAAAGCCTTGGTTACAATCCCAGAAACTACGTTCCAGACTGTTTCTTGG
CACTTCTGCATTGCTCTAGGTTACACAAACAGCTGCCTCAACCCAGTCCTTTATGCATTT
CTGGATGAAAACTTCAAACGATGCTTCAGAGAGTTCTGTATCCCAACCTCTTCCAACATT
GAGCAACAAAACTCCACTCGAATTCGTCAGAACACTAGAGACCACCCCTCCACGGCCAAT
ACAGTGGATAGAACTAATCATCAGCTAGAAAATCTGGAAGCAGAAACTGCTCCGTTGCCC
TAA
Target 5 GenBank Gene ID
Target 5 GeneCard ID OPRM1 Link Image
Target 5 GenAtlas ID OPRM1 Link Image
Target 5 HGNC ID HGNC:8156 Link Image
Target 5 Chromosome Location 6
Target 5 Locus 6q24-q25
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. Uhl GR, Sora I, Wang Z: The mu opiate receptor as a candidate gene for pain: polymorphisms, variations in expression, nociception, and opiate responses. Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7752-5. [PubMed Link Image]
  2. Chuang TK, Killam KF Jr, Chuang LF, Kung HF, Sheng WS, Chao CC, Yu L, Chuang RY: Mu opioid receptor gene expression in immune cells. Biochem Biophys Res Commun. 1995 Nov 22;216(3):922-30. [PubMed Link Image]
  3. Mestek A, Hurley JH, Bye LS, Campbell AD, Chen Y, Tian M, Liu J, Schulman H, Yu L: The human mu opioid receptor: modulation of functional desensitization by calcium/calmodulin-dependent protein kinase and protein kinase C. J Neurosci. 1995 Mar;15(3 Pt 2):2396-406. [PubMed Link Image]
  4. Wang JB, Johnson PS, Persico AM, Hawkins AL, Griffin CA, Uhl GR: Human mu opiate receptor. cDNA and genomic clones, pharmacologic characterization and chromosomal assignment. FEBS Lett. 1994 Jan 31;338(2):217-22. [PubMed Link Image]
  5. Bare LA, Mansson E, Yang D: Expression of two variants of the human mu opioid receptor mRNA in SK-N-SH cells and human brain. FEBS Lett. 1994 Nov 7;354(2):213-6. [PubMed Link Image]
  6. Bergen AW, Kokoszka J, Peterson R, Long JC, Virkkunen M, Linnoila M, Goldman D: Mu opioid receptor gene variants: lack of association with alcohol dependence. Mol Psychiatry. 1997 Oct-Nov;2(6):490-4. [PubMed Link Image]
  7. Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM, Tischfield JA, Kreek MJ, Yu L: Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9608-13. [PubMed Link Image]
Target 5 Drug 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 Link Image]
  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 Link Image]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  4. 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 Link Image]
  5. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [PubMed Link Image]
  6. 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 Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.