- Overview
- Properties
- Genetics
- Related Genes
- Related Drugs
- Related Diseases
- Datasets
- Downloads/LinkOuts
Overview
| Generic Names: | Tramadol HCl; Tramadol hydrochloride; Tramadolum [INN-Latin]; Tramodol Hcl; tramadol |
|---|---|
| Trade Names: | Crispin; Ralivia ER; Ralivia Flashtab; Tramadol HCl BP/EP; Tramal; Tridural; Ultram; Zydol |
| PharmGKB Accession Id: | PA451735 |
Description
A narcotic analgesic proposed for severe pain. It may be habituating. PubChem (source: Drug Bank)
Indication
Indicated in the treatment of moderate to severe pain. (source: Drug Bank)
ATC Therapeutic Category
- N02AX:Other opioids
Pharmacology, Interactions, and Contraindications
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. (source: Drug Bank)
Pharmacology
Tramadol, a centrally-acting analgesic, exists as a racemic mixture of the <i>trans</i> 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. (source: Drug Bank)
Absorption, Distribution, Metabolism, Elimination & Toxicity
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. (source: Drug Bank)
Protein Binding
20% (source: Drug Bank)
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. (source: Drug Bank)
Toxicity
LD<sub>50</sub>=350mg/kg (orally in mice) (source: Drug Bank)
Isomeric SMILES Code:
CN(C)C[C@H]1CCCC[C@@]1(c2cccc(c2)OC)O (source: Drug Bank)
In-Depth Annotations (
)
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rs59421388
at chr22:40853554
in
CYP2D6
This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.- Variant Name:
- CYP2D6: 3183G>A; 3271G>A
- Related Drugs:
- citalopram, codeine, desipramine, fluoxetine, fluvoxamine, gefitinib, haloperidol, imipramine, morphine, tramadol
- Related Diseases:
- Cystic Fibrosis, Depression, Hypertension, Neoplasms, Pain, Parkinson Disease, Schizophrenia
- Evidence:
-
http://www.pharmgkb.org/.../variant.jsp
-
rs61736512
at chr22:40855078
in
CYP2D6
This variant is part of the reduced functioning haplotype CYP2D6*29, which is found at an estimated allele frequency of 20% in African Tanzanians.- Variant Name:
- CYP2D6: 1659G>A; 1747G>A
- Related Drugs:
- citalopram, codeine, desipramine, fluoxetine, fluvoxamine, gefitinib, haloperidol, imipramine, morphine, tramadol
- Related Diseases:
- Cystic Fibrosis, Depression, Hypertension, Neoplasms, Pain, Parkinson Disease, Schizophrenia
- Evidence:
-
http://www.pharmgkb.org/.../variant.jsp
The following genes are in curated knowledge about this drug.
| Gene | Relationship | Evidence | |
|---|---|---|---|
|
CYP2B6 |
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Publications |
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CYP2D6 |
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Publications, Variants |
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CYP3A |
|
Publications |
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CYP3A4 |
|
Publications |
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CYP3A5 |
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Publications |
A list of non-curated publications that mention this drug along with other genes is available.
Drug Targets
| Gene | Description | |
|---|---|---|
| HTR2C |
|
(source: Drug Bank) |
| OPRK1 |
|
(source: Drug Bank) |
| OPRM1 |
|
(source: Drug Bank) |
| SLC6A2 |
|
(source: Drug Bank) |
| SLC6A4 |
|
(source: Drug Bank) |
The following drugs are in curated knowledge about this drug.
| Drug | Relationship | Evidence | |
|---|---|---|---|
|
|
warfarin |
|
Publications |
A list of non-curated publications that mention this drug along with other drugs is available.
Curated Information
The following diseases are in curated knowledge about this drug.
| Disease | Relationship | Evidence | |
|---|---|---|---|
|
|
Drug Hypersensitivity |
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Publications |
|
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Drug Toxicity |
|
Publications |
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Epidermal Necrolysis, Toxic |
|
Publications |
|
|
Pain |
|
Publications, Variants |
|
|
Stevens-Johnson Syndrome |
|
Publications |
Non-Curated Information
A list of non-curated publications that mention this drug along with other diseases is available.
Additional Datasets
These datasets are minimally curated and are sorted alphabetically by title.
LinkOuts
Common Searches
Search PubMed
Search Medline Plus
Search PubChem
Search CTD
Non-Curated Publications
A list of non-curated publications that mention this drug is available.