Identification

Name
Tramadol
Accession Number
DB00193  (APRD00028)
Type
Small Molecule
Groups
Approved, Investigational
Description

A narcotic analgesic proposed for moderate to severe pain. It may be habituating. Tramadol is also prepared as a variable release capsules, marketed under the brand name ConZip. For example, a 150 mg capsule will contain 37.5 mg of the immediate release form and 112.5 mg of the extended release form.

Structure
Thumb
Synonyms
  • (+)-Tramadol
  • (+)-trans-2-(Dimethylaminomethyl)-1-(m-methoxyphenyl)cyclohexanol
Product Ingredients
IngredientUNIICASInChI Key
Tramadol hydrochloride9N7R477WCK36282-47-0PPKXEPBICJTCRU-XMZRARIVSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ConZipCapsule, extended release200 mg/1OralVertical Pharmaceuticals, Inc.2011-08-312017-03-31Us
ConZipCapsule, extended release200 mg/1OralVertical Pharmaceuticals, LLC2011-08-31Not applicableUs
ConZipCapsule, extended release100 mg/1OralVertical Pharmaceuticals, Inc.2011-08-312017-02-28Us
ConZipCapsule, extended release100 mg/1OralVertical Pharmaceuticals, LLC2011-08-31Not applicableUs
ConZipCapsule, extended release300 mg/1OralVertical Pharmaceuticals, LLC2011-08-31Not applicableUs
ConZipCapsule, extended release300 mg/1OralVertical Pharmaceuticals, Inc.2011-08-312016-04-30Us
DurelaCapsule, extended release200 mgOralCipher Pharmaceuticals Inc.2012-03-19Not applicableCanada
DurelaCapsule, extended release100 mgOralCipher Pharmaceuticals Inc.2012-03-19Not applicableCanada
DurelaCapsule, extended release300 mgOralCipher Pharmaceuticals Inc.2012-03-19Not applicableCanada
RaliviaTablet, extended release200 mgOralValeant Canada Lp Valeant Canada S.E.C.2007-10-25Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RyzoltTablet, delayed release200 mg/1OralPd Rx Pharmaceuticals, Inc.2010-01-012014-10-13Us
Taro-tramadol ERTablet, extended release100 mgOralTaro Pharmaceuticals, Inc.2016-03-07Not applicableCanada
Taro-tramadol ERTablet, extended release300 mgOralTaro Pharmaceuticals, Inc.2016-05-27Not applicableCanada
Taro-tramadol ERTablet, extended release200 mgOralTaro Pharmaceuticals, Inc.2016-05-27Not applicableCanada
TramadolTablet50 mg/1OralAccord Healthcare Limited2017-10-232017-10-23Us
Tramadol ERTablet, extended release200 mg/1OralStat Rx USA2009-10-27Not applicableUs49884 0822 11 nlmimage10 b9125cd2
Tramadol HClTablet, film coated50 mg/1OralNorthwind Pharmaceuticals2017-10-03Not applicableUs
Tramadol HydrchlorideTablet50 mg/1OralRemedy Repack2012-03-092013-10-05Us65162 0627 11 nlmimage10 5212a925
Tramadol HydrochlorideTablet, film coated, extended release100 mg/1OralPar Pharmaceutical2012-06-27Not applicableUs
Tramadol HydrochlorideTablet, coated50 mg/1OralUnit Dose Services2010-11-15Not applicableUs50436 878720180907 15195 2u0b1k
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Act Tramadol/acetTramadol hydrochloride (37.5 mg) + Acetaminophen (325.0 mg)TabletOralActavis Pharma Company2012-05-01Not applicableCanada
Apo-tramadol/acetTramadol hydrochloride (37.5 mg) + Acetaminophen (325 mg)TabletOralApotex Corporation2009-11-09Not applicableCanada
Auro-tramadol/acetaminophenTramadol hydrochloride (37.5 mg) + Acetaminophen (325 mg)TabletOralAuro Pharma Inc2015-04-08Not applicableCanada
Ipg-tramadol/acetTramadol hydrochloride (37.5 mg) + Acetaminophen (325 mg)TabletOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada
Jamp-acet-tramadolTramadol hydrochloride (37.5 mg) + Acetaminophen (325 mg)TabletOralJamp Pharma Corporation2012-09-05Not applicableCanada
Lupin-tramadol/acetTramadol hydrochloride (37.50 mg) + Acetaminophen (325.00 mg)TabletOralLupin PharmaNot applicableNot applicableCanada
Mar-tramadol/acetTramadol hydrochloride (37.5 mg) + Acetaminophen (325 mg)TabletOralMarcan Pharmaceuticals Inc2012-09-04Not applicableCanada
Mint-tramadol/acetTramadol hydrochloride (37.5 mg) + Acetaminophen (325 mg)TabletOralMint Pharmaceuticals Inc2012-09-18Not applicableCanada
Mylan-tramadol/acetTramadol hydrochloride (37.5 mg) + Acetaminophen (325 mg)TabletOralMylan Pharmaceuticals2015-01-302017-05-08Canada
Pat-tramadol/acetTramadol hydrochloride (37.5 mg) + Acetaminophen (325 mg)TabletOralPatriot A Division Of Janssen Inc2012-08-142014-11-11Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
SynaprynTramadol hydrochloride (5 g/5g)KitOralFusion Pharmaceuticals LLC2009-09-142010-07-20Us
SynaprynTramadol hydrochloride (5.8 g/5.8g)KitCalifornia Pharmaceuticals, Llc2017-05-01Not applicableUs
Theratramadol-60Tramadol hydrochloride (50 mg/1) + gamma-Aminobutyric acid (100 mg/1)KitPhysician Therapeutics Llc2011-05-20Not applicableUs
Theratramadol-90Tramadol hydrochloride (50 mg/1) + gamma-Aminobutyric acid (100 mg/1)KitPhysician Therapeutics Llc2011-02-04Not applicableUs
Topical PainTramadol (0.1 g/100mL) + Diazepam (0.1 g/100mL) + Hydrocodone (0.1 g/100mL) + Ibuprofen (0.1 g/100mL)CreamTopicalDr Marc's Manufacturing And Sales2016-02-232018-04-18Us
TramapapTramadol hydrochloride (1 g/1g) + Acetaminophen (1 g/1g)KitLiving Well Pharmacy, Inc.2010-04-07Not applicableUs
International/Other Brands
Rybix / Tramal (Grünenthal GmbH)
Categories
UNII
0NG5TTM63P
CAS number
27203-92-5
Weight
Average: 263.3752
Monoisotopic: 263.188529049
Chemical Formula
C16H25NO2
InChI Key
TVYLLZQTGLZFBW-ZBFHGGJFSA-N
InChI
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
IUPAC Name
(1R,2R)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexan-1-ol
SMILES
COC1=CC=CC(=C1)[C@@]1(O)CCCC[C@@H]1CN(C)C

Pharmacology

Indication

Indicated in the treatment of moderate to severe pain. Consider for those prone to constipation or respiratory depression. Tramadol is used to treat postoperative, dental, cancer, and acute musculosketetal pain and as an adjuvant to NSAID therapy in patients with osteoarthritis.

Associated Conditions
Pharmacodynamics

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 its mode of action is not completely understood, from animal tests, at least two complementary mechanisms appear applicable: binding of parent and M1 metabolite to μ-opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin. Opioid activity is due to both low affinity binding of the parent compound and higher affinity binding of the O-demethylated metabolite M1 to μ-opioid receptors. In animal models, M1 is up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in μ-opioid binding. Opiate antagonist naloxone only partially antagonized tramadol-induced analgesia.

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.

TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
ASodium-dependent noradrenaline transporter
inhibitor
Human
ASodium-dependent serotonin transporter
inhibitor
Human
U5-hydroxytryptamine receptor 2C
antagonist
Human
UKappa-type opioid receptor
agonist
Human
NDelta-type opioid receptor
agonist
Human
UGlutamate receptor ionotropic, NMDA 3A
antagonist
Human
UAlpha-7 nicotinic cholinergic receptor subunit
antagonist
Human
UMuscarinic acetylcholine receptor M3
antagonist
Human
UMuscarinic acetylcholine receptor M1
antagonist
Human
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.

Volume of distribution
  • 2.6 L/kg [male, 100 mg intravenous dose]
  • 2.9 L/kg [female, 100 mg intravenous dose]
Protein binding

20% bound to plasma proteins.

Metabolism

Hepatic. 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. CYP3A4 and CYP2B6 facilitates the biotransformation of tramadol to N-desmethyl-tramadol. CYP2D6 facilitates the biotransformation of tramadol to O-desmethyl-tramadol.

Route of elimination

Tramadol is eliminated primarily through metabolism by the liver and the metabolites are excreted primarily by the kidneys. Approximately 30% of the dose is excreted in the urine as unchanged drug, whereas 60% of the dose is excreted as metabolites.

Half life

Tramadol and its metabolites are excreted primarily in the urine with observed plasma half-lives of 6.3 and 7.4 hours for tramadol and M1, respectively.

Clearance
  • 5.9 mL/min/Kg [Healthy Adults, 100 mg qid, MD p.o]
  • 8.5 mL/min/Kg [Healthy Adults, 100 mg SD p.o]
  • 6.89 mL/min/Kg [Geriatric, (<75 yr), 50 mg SD p.o.]
  • 4.23 mL/min/Kg [Hepatic Impaired, 50 mg SD p.o.]
  • 4.23 mL/min/Kg [Renal Impaired, Clcr10-3mL/min, 100 mg SD i.v.]
  • 3.73 mL/min/Kg [Renal Impaired, CLcr<5 mL/min, 100 mg SD i.v.]
  • 6.4 mL/min/Kg [Male following a 100 mg IV dose]
  • 5.7 mL/min/Kg [Female following a 100 mg IV dose]
Toxicity

LD50=350mg/kg (orally in mice)

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Tramadol Metabolism PathwayDrug metabolism
Tramadol Action Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all ADR Inferred EffectPoor drug metabolizer. This results in reduced analgesic efficacy and decreased risk of opioid toxicity as well as increased risk of seizures and serotonin syndrome. Consider alternative therapies.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Tramadol is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Tramadol is combined with (S)-Warfarin.
1,10-PhenanthrolineThe therapeutic efficacy of Tramadol can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Tramadol is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Tramadol is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Tramadol is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Tramadol.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Tramadol is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Tramadol.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Tramadol is combined with 4-Methoxyamphetamine.
Food Interactions
  • Oral administration of tramadol hydrochloride with food does not significantly affect its rate or extent of absorption, therefore, tramadol hydrochloride can be administered without regard to food.

References

Synthesis Reference

Wolfgang Reimann, "Combination preparation containing tramadol and a calcium channel antagonist." U.S. Patent US5929122, issued March, 1993.

US5929122
General References
  1. Dayer P, Desmeules J, Collart L: [Pharmacology of tramadol]. Drugs. 1997;53 Suppl 2:18-24. [PubMed:9190321]
  2. 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]
  3. 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]
  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:9190323]
  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]
External Links
Human Metabolome Database
HMDB0014339
KEGG Drug
D08623
KEGG Compound
C07153
PubChem Compound
33741
PubChem Substance
46506256
ChemSpider
31105
BindingDB
50176259
ChEBI
75725
ChEMBL
CHEMBL1066
Therapeutic Targets Database
DAP000140
PharmGKB
PA451735
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tramadol
ATC Codes
N02AX52 — Tramadol, combinationsN02AX02 — Tramadol
AHFS Codes
  • 28:08.08 — Opiate Agonists
FDA label
Download (408 KB)
MSDS
Download (74.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers4
1CompletedNot AvailableOsteoarthritis Thumbs1
1CompletedNot AvailablePain NOS1
1CompletedNot AvailableTo Determine Bioequivalence Under Fasting Conditions1
1CompletedBasic ScienceAging / Pain NOS1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedDiagnosticOsteoarthritis (OA)1
1CompletedOtherTo Determine Bioequivalence Under Fed Conditions1
1CompletedTreatmentBioavailability / Healthy Volunteers / Pharmacokinetics1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentPain NOS5
1, 2CompletedBasic ScienceOpioid Induced Motor Disturbances1
1, 2CompletedTreatmentOpioid Abuse / Opioid Addiction / Stimulant Abuse / Stimulant Addiction1
1, 2CompletedTreatmentOpioid Addiction / Opioid Dependence / Opioid Related Disorders1
1, 2CompletedTreatmentOpioid-Related Disorders1
1, 2CompletedTreatmentPain Management / Pulpitis dental1
1, 2Unknown StatusTreatmentChoroidal Melanoma / Eye Neoplasms / Melanoma1
2CompletedPreventionOpioid Analgesic Adverse Reaction / Traumas1
2CompletedSupportive CarePain NOS2
2CompletedTreatmentFibromyalgia / Human Growth Hormone Deficiency1
2CompletedTreatmentGeriatric Hip Fracture Pain Management1
2CompletedTreatmentOpioid-Related Disorders1
2CompletedTreatmentPain NOS1
2CompletedTreatmentPain, Acute1
2Not Yet RecruitingPreventionPost Anaesthetic Shivering1
2Not Yet RecruitingTreatmentTramadol for Labor Analgesia1
2RecruitingPreventionPain, Neuropathic1
2RecruitingSupportive CareCancer, Breast1
2Unknown StatusTreatmentNausea / Pain NOS / Pruritus / Vertigo1
2, 3Active Not RecruitingDiagnosticCancer, Breast1
2, 3CompletedTreatmentSubstance Withdrawal Syndrome1
2, 3Not Yet RecruitingTreatmentAnterior Cruciate Ligament Rupture / Muscle Weakness1
3CompletedTreatmentAcute Low Back Pain1
3CompletedTreatmentAcute Post-surgical Pain1
3CompletedTreatmentAnaesthesia therapy1
3CompletedTreatmentAnalgesia / Neonatal Infections / Pain NOS1
3CompletedTreatmentBack Pain Lower Back1
3CompletedTreatmentDiabetic Neuropathies1
3CompletedTreatmentFibromyalgia1
3CompletedTreatmentAdjunct to general anesthesia therapy / Indwelling Urinary Catheter / Male Patients1
3CompletedTreatmentOpioids Use / Pain, Chronic1
3CompletedTreatmentPain During Labour1
3CompletedTreatmentPain NOS / Postoperative pain1
3CompletedTreatmentPain, Acute2
3CompletedTreatmentPain, Chronic4
3CompletedTreatmentPostoperative pain1
3Not Yet RecruitingPreventionPain, Procedure1
3Not Yet RecruitingTreatmentAnaesthesia therapy / Shock, Septic1
3Not Yet RecruitingTreatmentOpiate withdrawal symptoms / Opioid-Related Disorders1
3RecruitingOtherPain Management1
3RecruitingPreventionHysteroscopy2
3RecruitingPreventionHysteroscopy / Pain NOS1
3RecruitingPreventionPain NOS1
3RecruitingPreventionPain, Post Procedural / Procedural Pain1
3RecruitingTreatmentAbdominal Pain (AP)1
3RecruitingTreatmentAmitriptyline / Hansen's Disease / Leprosy Neuropathy / Pain, Neuropathic1
3RecruitingTreatmentOpioids Use / Shoulder Pain1
3RecruitingTreatmentPain Management1
3RecruitingTreatmentPain, Chronic1
3TerminatedNot AvailablePremature Ejaculation1
3Unknown StatusTreatmentHip Arthroplasty / Knee Replacement Surgery / Spinal Anaesthesia1
4CompletedNot AvailablePain, Chronic1
4CompletedNot AvailableRheumatic Diseases1
4CompletedHealth Services ResearchAnkylosing Spondylitis (AS)1
4CompletedPreventionDisease, Chronic1
4CompletedPreventionPostoperative pain1
4CompletedSupportive CarePost-Operative Nausea and Vomiting (PONV) / Postoperative pain1
4CompletedTreatmentAnalgesia, Postoperative / Heart Surgery Via Sternotomy1
4CompletedTreatmentArthroplasty1
4CompletedTreatmentBack Pain1
4CompletedTreatmentChildren / Inguinal Hernias1
4CompletedTreatmentChildren / Postoperative pain / Recovery of Function1
4CompletedTreatmentDiabetic Neuropathies1
4CompletedTreatmentFibromyalgia / Pain NOS1
4CompletedTreatmentFracture Bone / Pain NOS1
4CompletedTreatmentGall Stone Disease1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentHernia1
4CompletedTreatmentHysterectomy / Postoperative pain1
4CompletedTreatmentInadequate or Impaired Respiratory Function / Pain NOS1
4CompletedTreatmentInguinal Hernias / Postoperative pain1
4CompletedTreatmentMalignancies1
4CompletedTreatmentOsteoarthritis (OA)1
4CompletedTreatmentOsteoarthritis (OA) / Pain NOS1
4CompletedTreatmentPain NOS2
4CompletedTreatmentPain NOS / Tonsillitis1
4CompletedTreatmentPain, Acute1
4CompletedTreatmentOr Peripheral Nerve Injury (PNI) / Peripheral Neuropathic Pain (PNP) Due to Postherpetic Neuralgia (PHN)1
4CompletedTreatmentPostoperative pain4
4CompletedTreatmentPostoperative pain / Spinal Stenosis1
4CompletedTreatmentRenal Stones1
4CompletedTreatmentRotator Cuff Syndrome1
4Enrolling by InvitationTreatmentNonspecific Pain Post Traumatic Injury1
4Not Yet RecruitingHealth Services ResearchIUD Insertion Complication1
4Not Yet RecruitingPreventionPain NOS1
4Not Yet RecruitingSupportive CareHysteroscopy1
4Not Yet RecruitingTreatmentChild, Only / Postoperative pain / Sleep Disorder; Breathing-Related1
4Not Yet RecruitingTreatmentDysmenorrhea1
4Not Yet RecruitingTreatmentPerineal Pain1
4RecruitingPreventionCaesarean Sections1
4RecruitingPreventionNeoplasms, Brain1
4RecruitingSupportive CareColon Diverticulosis / Colonic Neoplasms / Constipation Drug Induced / Diverticulitis, Colonic / Ileus / Ileus paralytic / Ileus; Mechanical / Malignant Neoplasm of Colon / Occasional Constipation / Postoperative pain / Rectum Cancer / Rectum Neoplasm1
4RecruitingSupportive CareNeoplasms, Thyroid / Parathyroid Adenomas / Parathyroid Diseases / Parathyroid Hyperplasia / Thyroid Cancers / Thyroid Diseases / Thyroid Goitre / Thyroid Nodules1
4RecruitingTreatmentPain NOS1
4RecruitingTreatmentPost-Cesarean Section / Postoperative pain1
4RecruitingTreatmentSleep Apnea Syndrome1
4TerminatedTreatmentAnkylosing Spondylitis (AS) / Pain NOS1
4TerminatedTreatmentPain NOS1
4Unknown StatusNot AvailablePolyps, Nasal1
4Unknown StatusTreatmentDepression / Pain NOS1
4Unknown StatusTreatmentLaparoscopic Nissen Fundoplication1
4Unknown StatusTreatmentPain NOS1
4Unknown StatusTreatmentPost Operative Pain1
4Unknown StatusTreatmentPost Traumatic Stress Disorder (PTSD)1
4WithdrawnTreatmentDiabetic Polyneuropathy / Postherpetic Neuralgia1
Not AvailableActive Not RecruitingBasic ScienceHealthy Volunteers1
Not AvailableActive Not RecruitingTreatmentFlail Chest / General Surgery / Rib Fractures / Traumas1
Not AvailableCompletedNot AvailablePost-operative Patients Treated by Tramadol1
Not AvailableCompletedNot AvailablePostoperative pain / Pregnancy1
Not AvailableCompletedDiagnosticLumbar Disc Disease1
Not AvailableCompletedOtherPostoperative pain1
Not AvailableCompletedOtherTramadol - Anesthetics- Child - Circumcision1
Not AvailableCompletedSupportive CarePostoperative pain1
Not AvailableCompletedTreatmentCataracts1
Not AvailableCompletedTreatmentCaudal epidural block therapy / Cholecystectomy / Postoperative pain1
Not AvailableCompletedTreatmentCaudal epidural block therapy / Pain Management / Ultrasound1
Not AvailableCompletedTreatmentPeriapical Abscess1
Not AvailableCompletedTreatmentPost Cesarean Pain Management1
Not AvailableCompletedTreatmentPost-Operative Nausea and Vomiting (PONV)1
Not AvailableCompletedTreatmentPostoperative Sedation, Abdominal Surgery1
Not AvailableCompletedTreatmentPostoperative pain2
Not AvailableCompletedTreatmentPregnancy Termination1
Not AvailableCompletedTreatmentSpinal Stenosis of Lumbar Region1
Not AvailableEnrolling by InvitationSupportive CareCancer, Breast / Radical Mastectomy Surgery1
Not AvailableNot Yet RecruitingPreventionCervical Biopsy1
Not AvailableNot Yet RecruitingTreatmentCatheter Site Discomfort1
Not AvailableRecruitingTreatmentBack Pain Lower Back1
Not AvailableRecruitingTreatmentGeneral Surgery / Pain NOS / Rib Fractures / Traumas1
Not AvailableRecruitingTreatmentPostoperative Sedation,Gastrectomy, Enhanced Recovery After Surgery1
Not AvailableRecruitingTreatmentSecond Degree Burns1
Not AvailableTerminatedNot AvailablePain, Chronic1
Not AvailableTerminatedScreeningCytochrome P450 Phenotype and Genotype Metrics1
Not AvailableUnknown StatusTreatmentPain Relief1
Not AvailableUnknown StatusTreatmentPeritonsillar Abscess1
Not AvailableUnknown StatusTreatmentPostoperative pain1
Not AvailableWithdrawnTreatmentPostoperative pain1

Pharmacoeconomics

Manufacturers
  • Cipher pharmaceuticals inc
  • Purdue pharma products lp
  • Par pharmaceutical
  • Biovail laboratories international srl
  • Victory pharma inc
  • Actavis elizabeth llc
  • Alphapharm party ltd
  • Amneal pharmaceuticals llc
  • Apotex inc
  • Asta medica inc
  • Caraco pharmaceutical laboratories ltd
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mallinckrodt inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Northstar healthcare holdings ltd
  • Pliva inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories
  • Ortho mcneil janssen pharmaceuticals inc
Packagers
  • 4uOrtho LLC
  • Able Laboratories Inc.
  • Advanced Pharmaceutical Services Inc.
  • Alphapharm Party Ltd.
  • Altura Pharmaceuticals Inc.
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotex Inc.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • BC Vision Inc.
  • Biovail Pharmaceuticals
  • Blenheim Pharmacal
  • Bryant Ranch Prepack
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Concern Stirol
  • Confab Laboratories Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • D.M. Graham Laboratories Inc.
  • Deca Pharmaceuticals LLC
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • Fusion Pharmaceuticals LLC
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Ivax Pharmaceuticals
  • Janssen-Ortho Inc.
  • Kali Laboratories Inc.
  • Keltman Pharmaceuticals Inc.
  • Labopharm Inc.
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • McNeil Laboratories
  • Medisca Inc.
  • Medvantx Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Patriot Pharmaceuticals
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Piramal Healthcare
  • Pliva Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescription Dispensing Service Inc.
  • Purdue Pharma LP
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Ropack Inc.
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • Trinity Laboratories Inc.
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Va Cmop Dallas
  • Vangard Labs Inc.
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
Capsule, extended releaseOral100 mg/1
Capsule, extended releaseOral200 mg/1
Capsule, extended releaseOral300 mg/1
Capsule, extended releaseOral100 mg
Capsule, extended releaseOral200 mg
Capsule, extended releaseOral300 mg
Tablet, delayed releaseOral200 mg/1
Kit5.8 g/5.8g
KitOral5 g/5g
CreamTopical
TabletOral
TabletOral50 mg/1
CapsuleOral150 mg/1
Capsule, coated, extended releaseOral150 mg/1
Capsule, extended releaseOral150 mg/1
TabletOral50 mg/50mg
Tablet, coatedOral200 mg/1
Tablet, film coatedOral50 mg/1
Tablet, film coatedOral
CapsuleOral100 mg/1
CapsuleOral200 mg/1
CapsuleOral300 mg/1
Tablet, film coated, extended releaseOral100 mg/1
Tablet, film coated, extended releaseOral200 mg/1
Tablet, film coated, extended releaseOral300 mg/1
Kit
Tablet, extended releaseOral100 mg
Tablet, coatedOral
TabletOral50 mg
Tablet, coatedOral50 mg/1
Tablet, coatedOral50 mg/201
Tablet, orally disintegratingOral50 mg/1
TabletOral100 mg/1
Tablet, extended releaseOral100 mg/1
Tablet, extended releaseOral200 mg/1
Tablet, extended releaseOral300 mg/1
Tablet, extended releaseOral150 mg
Tablet, extended releaseOral200 mg
Tablet, extended releaseOral300 mg
Tablet, extended releaseOral400 mg
Tablet, extended releaseOral75 mg
Prices
Unit descriptionCostUnit
Tramadol hcl powder29.08USD g
Ultram ER 300 mg 24 Hour tablet10.66USD tablet
Ultram er 300 mg tablet10.25USD tablet
Ultram ER 200 mg 24 Hour tablet7.64USD tablet
Ultram er 200 mg tablet7.35USD tablet
TraMADol HCl 200 mg 24 Hour tablet6.25USD tablet
Ultram ER 100 mg 24 Hour tablet4.62USD tablet
Ultram er 100 mg tablet4.44USD tablet
TraMADol HCl 100 mg 24 Hour tablet3.78USD tablet
Ultram 50 mg tablet1.99USD tablet
Tramadol-Acetaminophen 37.5-325 mg tablet1.07USD tablet
Tramadol hcl 50 mg tablet0.7USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5464632No1995-11-072013-03-22Us
CA2476201No2009-09-012023-02-21Canada
CA2123160No2003-04-292014-05-09Canada
US6339105Yes2002-01-152020-04-12Us
US6106861No2000-08-222017-12-05Us
US6607748No2003-08-192020-06-29Us
US7988998No2011-08-022023-10-27Us
US7858118No2010-12-282022-04-11Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)180-181 °CNot Available
water solubilitySoluble Not Available
logP2.4FDA label
pKa9.41FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.75 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity78.27 m3·mol-1ChemAxon
Polarizability30.45 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9924
Blood Brain Barrier+0.9382
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.6283
P-glycoprotein inhibitor IInhibitor0.7807
P-glycoprotein inhibitor IIInhibitor0.9589
Renal organic cation transporterNon-inhibitor0.6398
CYP450 2C9 substrateNon-substrate0.7678
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.7726
CYP450 1A2 substrateNon-inhibitor0.7136
CYP450 2C9 inhibitorNon-inhibitor0.704
CYP450 2D6 inhibitorInhibitor0.6566
CYP450 2C19 inhibitorNon-inhibitor0.6841
CYP450 3A4 inhibitorNon-inhibitor0.6256
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7832
Ames testNon AMES toxic0.7899
CarcinogenicityNon-carcinogens0.6663
BiodegradationNot ready biodegradable0.9975
Rat acute toxicity3.0316 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6136
hERG inhibition (predictor II)Inhibitor0.7098
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-9010000000-ffea37e400f0860f2e7f
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-0090000000-7850be0ba78033f1f677
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-0090000000-62a3c5cb6717bff20e2c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05fs-0930000000-b8297a71c45e9630f6c0
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05fr-0900000000-f650c49b70db20869d0f
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0adl-0900000000-b17dfc32e2eb57efaf42
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0090000000-c35bec467cfec28511fb
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-1090000000-9ca08dcdc5a2027bcb03
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9030000000-469467d2583e7202d89f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9000000000-89f055b497c88cdc5e79
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9000000000-1922068301c6d3b4f457
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9000000000-1922068301c6d3b4f457
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9000000000-5a9396f20ce15b9c08ba
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-1090000000-e040861e9fa18a8f44a5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9030000000-fa1522b6a491e6da41c9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9000000000-8ab0ebc3ceff7c5e5ce5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9000000000-7645dc9b29d8b2867495
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9000000000-70cad0a31ff2d57bab81
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9000000000-bf1b2c15c6511355c9e1
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0090000000-02e5642feacadbc07dba
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0abi-0900000000-5e83a9ee1a223ef36905
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0900000000-56f60436c6df4aeb6515
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0090000000-1336e1f66542750cc1de
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0090000000-0f15435bd2e7f629a898
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-0090000000-1550dc2447717d7d8728

Taxonomy

Description
This compound belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Anisoles
Direct Parent
Anisoles
Alternative Parents
Phenoxy compounds / Methoxybenzenes / Cyclohexanols / Aralkylamines / Alkyl aryl ethers / Tertiary alcohols / Trialkylamines / Cyclic alcohols and derivatives / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Phenoxy compound / Anisole / Methoxybenzene / Alkyl aryl ether / Cyclohexanol / Aralkylamine / Monocyclic benzene moiety / Tertiary alcohol / Cyclic alcohol / Tertiary aliphatic amine
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol (CHEBI:75725)

Targets

Details
1. Mu-type opioid receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Voltage-gated calcium channel activity
Specific Function
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
Molecular Weight
44778.855 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. 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]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
Molecular Weight
42644.665 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
Molecular Weight
40368.235 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein phosphatase 2a binding
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 ...
Gene Name
GRIN3A
Uniprot ID
Q8TCU5
Uniprot Name
Glutamate receptor ionotropic, NMDA 3A
Molecular Weight
125464.07 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Not Available
Specific Function
Not Available
Gene Name
CHRNA7
Uniprot ID
Q693P7
Uniprot Name
Alpha-7 nicotinic cholinergic receptor subunit
Molecular Weight
2987.635 Da
References
  1. Shiraishi M, Minami K, Uezono Y, Yanagihara N, Shigematsu A, Shibuya I: Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing alpha 7 receptors. Br J Pharmacol. 2002 May;136(2):207-16. [PubMed:12010769]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor activity
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...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
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...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
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]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [PubMed:15509185]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase 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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Subrahmanyam V, Renwick AB, Walters DG, Young PJ, Price RJ, Tonelli AP, Lake BG: Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. Drug Metab Dispos. 2001 Aug;29(8):1146-55. [PubMed:11454734]
  2. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [PubMed:15509185]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase 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 un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Subrahmanyam V, Renwick AB, Walters DG, Young PJ, Price RJ, Tonelli AP, Lake BG: Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. Drug Metab Dispos. 2001 Aug;29(8):1146-55. [PubMed:11454734]
  2. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [PubMed:15509185]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [PubMed:15304429]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 04:39