ContaminantDB: Tramadol

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (9)XML

Record Information

Version

1.0

Creation Date

2009-07-05 03:34:13 UTC

Update Date

2026-03-25 19:47:11 UTC

Accession Number

CHEM002099

Identification

Common Name

Tramadol

Class

Small Molecule

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. Tramadol is only found in individuals that have used or taken this drug. It is a narcotic analgesic proposed for moderate to severe pain. It may be habituating. 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.

Contaminant Sources

HMDB Contaminants - Urine
STOFF IDENT Compounds
Suspected Compounds
Suspected Compounds - Waste Water
Suspected Compounds – Schymanski Project
T3DB toxins

Contaminant Type

Amine
Analgesic
Analgesic, Opioid
Drug
Ether
Metabolite
Narcotic
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(+)-Tramadol	ChEBI
(+)-trans-2-(Dimethylaminomethyl)-1-(m-methoxyphenyl)cyclohexanol	ChEBI
Amanda	Kegg
1a Brand OF tramadol hydrochloride	HMDB
ASTA medica brand OF tramadol hydrochloride	HMDB
AbZ brand OF tramadol hydrochloride	HMDB
Adolonta	HMDB
Bayvit brand OF tramadol hydrochloride	HMDB
Bexal brand OF tramadol hydrochloride	HMDB
Dolorgiet brand OF tramadol hydrochloride	HMDB
Edigen brand OF tramadol hydrochloride	HMDB
Hexal brand OF tramadol hydrochloride	HMDB
Lindopharm brand OF tramadol hydrochloride	HMDB
MTW Brand OF tramadol hydrochloride	HMDB
MTW Tramadol	HMDB
Mabo brand OF tramadol hydrochloride	HMDB
Q-Pharm brand OF tramadol hydrochloride	HMDB
Rowa brand OF tramadol hydrochloride	HMDB
Theraplix brand OF tramadol hydrochloride	HMDB
Tradol-puren	HMDB
TradolPuren	HMDB
Trama 1a pharma	HMDB
Trama KD	HMDB
Tramadol asta medica	HMDB
Tramadol bexal	HMDB
Tramadol edigen	HMDB
Tramadol ratiopharm	HMDB
TramadolHameln	HMDB
Ultram	HMDB
Zydol	HMDB
Alpharma brand OF tramadol hydrochloride	HMDB
Biodalgic	HMDB
Byk brand OF tramadol hydrochloride	HMDB
Ciclum brand OF tramadol hydrochloride	HMDB
Cinfa brand OF tramadol hydrochloride	HMDB
Clonmel brand OF tramadol hydrochloride	HMDB
Contramal	HMDB
Elerte brand OF tramadol hydrochloride	HMDB
Expanscience brand OF tramadol hydrochloride	HMDB
Hameln brand OF tramadol hydrochloride	HMDB
Jutadol	HMDB
Knoll brand OF tramadol hydrochloride	HMDB
Krewel brand OF tramadol hydrochloride	HMDB
MTWTramadol	HMDB
Medix brand OF tramadol hydrochloride	HMDB
TAD brand OF tramadol hydrochloride	HMDB
Theradol	HMDB
Tiral	HMDB
Tradol puren	HMDB
Tradonal	HMDB
Trama-dorsch	HMDB
TramaDorsch	HMDB
Tramadin	HMDB
Tramadoc	HMDB
Tramadol 1a	HMDB
Tramadol al	HMDB
Tramadol bayvit	HMDB
Tramadol mabo	HMDB
Tramadol PB	HMDB
Tramadol acis	HMDB
TramadolDolgit	HMDB
Tramadolor	HMDB
Tramagetic	HMDB
Tramagit	HMDB
Zambon brand OF tramadol hydrochloride	HMDB
Zamudol	HMDB
Zytram	HMDB
Betapharm brand OF tramadol hydrochloride	HMDB
Aliud brand OF tramadol hydrochloride	HMDB
Amadol	HMDB
CSL Brand OF tramadol hydrochloride	HMDB
Christiaens brand OF tramadol hydrochloride	HMDB
Erempharma brand OF tramadol hydrochloride	HMDB
Grunenthal brand OF tramadol hydrochloride	HMDB
Heumann brand OF tramadol hydrochloride	HMDB
Juta brand OF tramadol hydrochloride	HMDB
Kern brand OF tramadol hydrochloride	HMDB
Lakeside brand OF tramadol hydrochloride	HMDB
Lichtenstein brand OF tramadol hydrochloride	HMDB
Mundipharma brand OF tramadol hydrochloride	HMDB
Nobligan	HMDB
Ortho brand OF tramadol hydrochloride	HMDB
Ranitidin 1a pharma	HMDB
Ratiopharm brand OF tramadol hydrochloride	HMDB
Searle brand OF tramadol hydrochloride	HMDB
Stadapharm brand OF tramadol hydrochloride	HMDB
Takadol	HMDB
Topalgic	HMDB
Tradol	HMDB
Tralgiol	HMDB
Trama abz	HMDB
Tramadol hydrochloride	HMDB
Tramadol normon	HMDB
Tramadol-hameln	HMDB
Tramadol-ratiopharm	HMDB
Tramadolratiopharm	HMDB
Tramake	HMDB
Trasedal	HMDB
Viatris brand OF tramadol	HMDB
Acis brand OF tramadol hydrochloride	HMDB
Allphar brand OF tramadol hydrochloride	HMDB
Antigen brand OF tramadol hydrochloride	HMDB
Azupharma brand OF tramadol hydrochloride	HMDB
Basics brand OF tramadol hydrochloride	HMDB
Biocodex brand OF tramadol hydrochloride	HMDB
Biokanol	HMDB
Docpharm brand OF tramadol hydrochloride	HMDB
Janssen brand OF tramadol hydrochloride	HMDB
Kade brand OF tramadol hydrochloride	HMDB
MTW-Tramadol	HMDB
Merck dura brand OF tramadol hydrochloride	HMDB
Normon brand OF tramadol hydrochloride	HMDB
Prontofort	HMDB
Q Pharm brand OF tramadol hydrochloride	HMDB
Trama dorsch	HMDB
Tramabeta	HMDB
Tramadol basics	HMDB
Tramadol cinfa	HMDB
Tramadol dolgit	HMDB
Tramadol hameln	HMDB
Tramadol heumann	HMDB
Tramadol kern	HMDB
Tramadol lichtenstein	HMDB
Tramadol lindo	HMDB
Tramadol stada	HMDB
Tramadol viatris brand	HMDB
Tramadol-dolgit	HMDB
Tramadura	HMDB
Tramal	HMDB
Tramex	HMDB
Tramundin	HMDB
Xymel 50	HMDB
Zumalgic	HMDB

Chemical Formula

C₁₆H₂₅NO₂

Average Molecular Mass

263.375 g/mol

Monoisotopic Mass

263.189 g/mol

CAS Registry Number

27203-92-5

IUPAC Name

(1R,2R)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexan-1-ol

Traditional Name

tramadol

SMILES

COC1=CC=CC(=C1)[C@@]1(O)CCCC[C@@H]1CN(C)C

InChI Identifier

InChI=1S/C16H25NO2/c1-17(2)12-14-7-4-5-10-16(14,18)13-8-6-9-15(11-13)19-3/h6,8-9,11,14,18H,4-5,7,10,12H2,1-3H3/t14-,16+/m1/s1

InChI Key

TVYLLZQTGLZFBW-ZBFHGGJFSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof.

Kingdom

Super Class

Class

Sub Class

Direct Parent

Alternative Parents

Substituents

Phenoxy compound
Anisole
Methoxybenzene
Alkyl aryl ether
Cyclohexanol
Aralkylamine
Monocyclic benzene moiety
Tertiary alcohol
Cyclic alcohol
Tertiary aliphatic amine
Tertiary amine
Ether
Organooxygen compound
Organonitrogen compound
Organopnictogen compound
Alcohol
Organic oxygen compound
Amine
Organic nitrogen compound
Hydrocarbon derivative
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol (CHEBI:75725 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

Solid (1).

Experimental Properties

Property	Value
Melting Point	180-181°C
Boiling Point	Not Available
Solubility	Soluble

Predicted Properties

Property	Value	Source
Water Solubility	0.75 g/L	ALOGPS
logP	2.71	ALOGPS
logP	2.45	ChemAxon
logS	-2.6	ALOGPS
pKa (Strongest Acidic)	13.8	ChemAxon
pKa (Strongest Basic)	9.23	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	32.7 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	78.27 m³·mol⁻¹	ChemAxon
Polarizability	30.45 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4i-9650000000-250d842ef06233328170	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-05fr-5193000000-dd2e84f70a47d0634c43	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-03di-0090000000-1550dc2447717d7d8728	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-03di-0090000000-7850be0ba78033f1f677	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-03di-0090000000-62a3c5cb6717bff20e2c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-05fs-0930000000-b8297a71c45e9630f6c0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-05fr-0900000000-f650c49b70db20869d0f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0adl-0900000000-b17dfc32e2eb57efaf42	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0002-0090000000-c35bec467cfec28511fb	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-1090000000-9ca08dcdc5a2027bcb03	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0a4i-9030000000-469467d2583e7202d89f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0a4i-9000000000-89f055b497c88cdc5e79	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0a4i-9000000000-1922068301c6d3b4f457	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0a4i-9000000000-1922068301c6d3b4f457	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0a4i-9000000000-5a9396f20ce15b9c08ba	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-03di-1090000000-e040861e9fa18a8f44a5	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0a4i-9030000000-fa1522b6a491e6da41c9	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0a4i-9000000000-8ab0ebc3ceff7c5e5ce5	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0a4i-9000000000-7645dc9b29d8b2867495	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0a4i-9000000000-70cad0a31ff2d57bab81	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-ITFT , positive	splash10-0a4i-9000000000-bf1b2c15c6511355c9e1	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-01ot-0090000000-7fe9a41fb060355ba0c0	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0hft-1190000000-8c3c0de6df7ced23802a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0pbc-9120000000-4f0e74f6721de4ccf067	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-0090000000-24bef5bd2510914bee83	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03di-1490000000-3314217686d7d48bff0d	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4l-9380000000-76c818434cc5aeed5aca	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0a4i-9010000000-ffea37e400f0860f2e7f	Spectrum

Toxicity Profile

Route of Exposure

Inhalation. 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.

Mechanism of Toxicity

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.

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. 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. Tramadol undergoes hepatic metabolism via the cytochrome P450 isozyme CYP2D6, being O- and N-demethylated to five different metabolites. Of these, M1 (O-Desmethyltramadol) is the most significant since it has 200 times the affinity of (+)-tramadol, and furthermore has an elimination half-life of nine hours, compared with six hours for tramadol itself. In the 6% of the population that have slow CYP2D6 activity, there is therefore a slightly reduced analgesic effect. Phase II hepatic metabolism renders the metabolites water-soluble, which are excreted by the kidneys. Thus, reduced doses may be used in renal and hepatic impairment (1, 8). 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.

Toxicity Values

LD50: 300-350 mg/kg (Oral, Rat) (7)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

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 (1).

Minimum Risk Level

Not Available

Health Effects

Serious potential consequences of overdosage are respiratory depression, lethargy, coma, seizure, cardiac arrest and death. The respiratory depressant effects include carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure, and may be markedly exaggerated in these patients (RxList, A308). Medical problems can include congested lungs, liver disease, tetanus, infection of the heart valves, skin abscesses, anemia and pneumonia. Death can occur from overdose.

Symptoms

Overdose symptoms of a tramadol overdose may include drowsiness, shallow breathing, slow heartbeat, extreme weakness, cold or clammy skin, feeling light-headed, fainting, or coma. (9)

Treatment

In treating an overdose, primary attention should be given to maintaining adequate ventilation along with general supportive treatment. While naloxone will reverse some, but not all, symptoms caused by overdosage with ULTRAM, the risk of seizures is also increased with naloxone administration. (10)

Concentrations