Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C16H25NO2 |
Molecular Weight | 263.3752 |
Optical Activity | ( + ) |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(=CC=C1)[C@@]2(O)CCCC[C@@H]2CN(C)C
InChI
InChIKey=TVYLLZQTGLZFBW-ZBFHGGJFSA-N
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
Molecular Formula | C16H25NO2 |
Molecular Weight | 263.3752 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.drugs.com/tramadol.html | https://www.drugbank.ca/drugs/DB00193 | http://reference.medscape.com/drug/ultram-er-tramadol-343324 |
Curator's Comment: description was created based on several sources, including
https://www.drugs.com/tramadol.html | https://www.drugbank.ca/drugs/DB00193 | http://reference.medscape.com/drug/ultram-er-tramadol-343324 |
Tramadol (sold under the brand name Ultram) is a narcotic analgesic proposed for moderate to severe pain. 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 the 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. Tramadol is used primarily to treat mild-severe pain, both acute and chronic. Its analgesic effects take about one hour to come into effect and 2 h to 4 h to peak after oral administration with an immediate-release formulation. On a dose-by-dose basis, tramadol has about one-tenth the potency of morphine and is approximately equally potent when compared to pethidine and codeine. The most common adverse effects of tramadol include nausea, dizziness, dry mouth, indigestion, abdominal pain, vertigo, vomiting, constipation, drowsiness, and headache. Compared to other opioids, respiratory depression and constipation are considered less of a problem with tramadol.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900459 |
1300.0 nM [EC50] | ||
Target ID: CHEMBL237 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19027293 |
14.0 nM [Ki] | ||
Target ID: CHEMBL236 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19027293 |
9.4 nM [Ki] | ||
Target ID: CHEMBL228 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18242987 |
1493.0 nM [IC50] | ||
Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18242987 |
3861.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ULTRAM Approved UseTramadol hydrochloride extended-release tablets are indicated for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of their pain for an extended period of time. Launch Date1995 |
|||
Primary | ULTRAM Approved UseTramadol hydrochloride extended-release tablets are indicated for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of their pain for an extended period of time. Launch Date1995 |
|||
Primary | ULTRAM Approved UseTramadol hydrochloride extended-release tablets are indicated for the management of moderate to moderately severe chronic pain in adults who require around-the-clock treatment of their pain for an extended period of time. Launch Date1995 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
332 ng/mL |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TRAMADOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
70 ng/mL |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
O-DESMETHYLTRAMADOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5678 ng × h/mL |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TRAMADOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
|
1319 ng × h/mL |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
O-DESMETHYLTRAMADOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
80% |
200 mg 1 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
TRAMADOL plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
unlikely | ||||
Page: 9.0 |
yes | |||
Page: 5.0 |
yes | likely (co-administration study) Comment: Coadministration of quinidine, a selective inhibitor of CYP2D6, with tramadol ER resulted in a 50 60% increase in tramadol exposure; pharmacogenomic studies were also conducted: rapid conversion to active metabolite results in higher than expected serum M1 levels. Individuals who are ultra-rapid metabolizers should not use drug. Page: 5.0 |
||
Page: 5.0 |
yes | likely (co-administration study) Comment: The concomitant use of ULTRAM with cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir) or discontinuation of a cytochrome P450 3A4 inducer such as rifampin, carbamazepine, and phenytoin, may result in an increase in tramadol plasma concentrations; Concomitant administration of tramadol immediate-release tablets with cimetidine, a weak CPY3A4 inhibitor, does not result in clinically significant changes in tramadol pharmacokinetics; Page: 5.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 9.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Control of non-malignant chronic pain conditions in Japan and the possible future role of tramadol. | 2001 |
|
Single-dose dipyrone for acute postoperative pain. | 2001 |
|
Use of remifentanil in combination with desflurane or propofol for ambulatory oral surgery. | 2001 |
|
Nalbuphine by PCA-pump for analgesia following hysterectomy: bolus application versus continuous infusion with bolus application. | 2001 |
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Analgesic efficacy of tramadol 2 mg kg(-1) for paediatric day-case adenoidectomy. | 2001 Apr |
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A nonsurgical approach to low back pain. | 2001 Apr |
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Tramadol for postoperative shivering: a double-blind comparison with pethidine. | 2001 Apr |
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[Clinical remission of an HLA B27-positive sacroiliitis on vegan diet]. | 2001 Aug |
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Pharmacology of oral combination analgesics: rational therapy for pain. | 2001 Aug |
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Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. A quantitative systematic review. | 2001 Aug |
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Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. | 2001 Aug |
|
Validation of a high-performance liquid chromatography method for tramadol and o-desmethyltramadol in human plasma using solid-phase extraction. | 2001 Aug 15 |
|
Analgesic efficacy of tramadol if coadministered with ondansetron. | 2001 Dec |
|
The effects of two single doses of tramadol on sleep: a randomized, cross-over trial in healthy volunteers. | 2001 Jan |
|
[Adiuvants in the axillary brachial plexus blockade. Comparison between clonidine, sufentanil and tramadol]. | 2001 Jan-Feb |
|
Investigation of racial variations in the metabolism of tramadol. | 2001 Jan-Jun |
|
Metabolism of the analgesic drug, tramadol hydrochloride, in rat and dog. | 2001 Jul |
|
Comparison of caudal morphine and tramadol for postoperative pain control in children undergoing inguinal herniorrhaphy. | 2001 Jul |
|
Caudal bupivacaine-tramadol combination for postoperative analgesia in pediatric herniorrhaphy. | 2001 Jul |
|
[Chronic pain in geriatrics]. | 2001 Jun |
|
Anesthetic considerations in a patient with visceral leishmaniasis. | 2001 Jun |
|
Tramadol dependence with no history of substance abuse. | 2001 Jun |
|
Direct tramadol application on sciatic nerve inhibits spinal somatosensory evoked potentials in rats. | 2001 Jun |
|
Tramadol, an alternative to morphine for treating posttraumatic pain in the prehospital situation. | 2001 Jun |
|
Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects. | 2001 Mar |
|
Pharmacotherapy for nonmalignant pain. | 2001 Mar 1 |
|
Role of tramadol in reducing pain on propofol injection. | 2001 May |
|
NSAIDS, COX-2 inhibitors and tramadol: acute postoperative pain management in day-case surgery patients. | 2001 May |
|
[Pain in elderly patients and aspects of its therapy]. | 2001 May 24 |
|
A comparison of tramadol, amitriptyline, and meperidine for postepidural anesthetic shivering in parturients. | 2001 Nov |
|
Acetaminophen, aspirin, or Ibuprofen in combination analgesic products. | 2001 Nov-Dec |
|
Distribution of enantiomers of trans-tramadol and trans-O-demethyltramadol in central nervous system of rats. | 2001 Oct |
|
Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial. | 2001 Sep |
|
Managing postoperative pain. | 2001 Sep |
|
Controlled release of tramadol hydrochloride from matrices prepared using glyceryl behenate. | 2001 Sep |
|
Psychosomatic reactions to a stressful environment and an attempt at pharmacological modification. | 2001 Sep-Oct |
|
New, non-NSAID alternative. | 2002 Feb |
|
Combination analgesic efficacy: individual patient data meta-analysis of single-dose oral tramadol plus acetaminophen in acute postoperative pain. | 2002 Feb |
|
[Recovery of lung function after laparoscopic cholecystectomy: the role of postoperative pain]. | 2002 Feb |
|
The addition of tramadol to lidocaine does not reduce tourniquet and postoperative pain during iv regional anesthesia. | 2002 Feb |
|
Use of nonopioid analgesics and adjunctive agents in the management of pain in rheumatic diseases. | 2002 Jan |
|
Physical compatibility and in vivo evaluation of drug mixtures for subcutaneous infusion to cancer patients in palliative care. | 2002 Jan |
Sample Use Guides
Chronic: 25 mg PO every morning initially; increased by 25-50 mg/day every 3 days up to 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day
Acute: 50-100 mg PO q4-6hr PRN; not to exceed 400 mg/day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27383307
A malignancy of A549 and PC-9 cells was detected after treatment of 2 μM tramadol for different time (0, 7, 14, or 28 d).
The effect of tramadol on the invasion of A549 and PC-9 cells was performed using transwell chambers (6.5 mm diameter and 8 μm pore size; Millipore, Billerica, MA, USA). After treated with 2 μM tramadol for various time, cells were plated onto the Matrigel-coated upper part of the transwell chamber, fetal bovine serum (FBS) medium (20%) was added to the lower wells as a chemoattractant. 48 hours later, non-invading cells were removed, the invaded cells were fixed with 4% paraformaldehyde for 30 min and stained with 1% crystal violet for 30 min. The number of stained cells on the undersurface of the polycarbonate membranes was then counted visually in five random image fields at 200 × magnifications using a microscope (Olympus, Lake Success, NY, USA).
Substance Class |
Chemical
Created
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admin
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Edited
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Record UNII |
0NG5TTM63P
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Record Status |
Validated (UNII)
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Record Version |
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33741
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123154-38-1
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0NG5TTM63P
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Related Record | Type | Details | ||
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TARGET -> AGONIST | |||
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TARGET -> INHIBITOR | |||
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ENANTIOMER -> ENANTIOMER |
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RACEMATE -> ENANTIOMER |
Agonist of the ?. opioid receptor and inhibits serotonin reuptake.
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