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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
Structure of TRAMADOL, (+)-

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

HIDE SMILES / InChI

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

Description
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.

Originator

Sources: Oyo Yakuri (1973), 7, (7), 1087-95.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1300.0 nM [EC50]
14.0 nM [Ki]
9.4 nM [Ki]
1493.0 nM [IC50]
3861.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ULTRAM

Approved Use

Tramadol 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 Date

1995
Primary
ULTRAM

Approved Use

Tramadol 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 Date

1995
Primary
ULTRAM

Approved Use

Tramadol 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 Date

1995
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
unlikely
yes
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
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;
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Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
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
Analgesic efficacy of tramadol 2 mg kg(-1) for paediatric day-case adenoidectomy.
2001 Apr
A nonsurgical approach to low back pain.
2001 Apr
Tramadol for postoperative shivering: a double-blind comparison with pethidine.
2001 Apr
[Clinical remission of an HLA B27-positive sacroiliitis on vegan diet].
2001 Aug
Pharmacology of oral combination analgesics: rational therapy for pain.
2001 Aug
Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. A quantitative systematic review.
2001 Aug
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
Patents

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
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
by admin
on Mon Mar 31 23:10:32 GMT 2025
Edited
by admin
on Mon Mar 31 23:10:32 GMT 2025
Record UNII
0NG5TTM63P
Record Status Validated (UNII)
Record Version
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Name Type Language
(+)-(R,R)-TRAMADOL
Preferred Name English
TRAMADOL, (+)-
Common Name English
(1R,2R)-2-((DIMETHYLAMINO)METHYL)-1-(3-METHOXYPHENYL)CYCLOHEXANOL
Common Name English
(+)-TRAMADOL
Common Name English
Code System Code Type Description
EPA CompTox
DTXSID401167150
Created by admin on Mon Mar 31 23:10:32 GMT 2025 , Edited by admin on Mon Mar 31 23:10:32 GMT 2025
PRIMARY
PUBCHEM
33741
Created by admin on Mon Mar 31 23:10:32 GMT 2025 , Edited by admin on Mon Mar 31 23:10:32 GMT 2025
PRIMARY
CHEBI
75725
Created by admin on Mon Mar 31 23:10:32 GMT 2025 , Edited by admin on Mon Mar 31 23:10:32 GMT 2025
PRIMARY
CAS
123154-38-1
Created by admin on Mon Mar 31 23:10:32 GMT 2025 , Edited by admin on Mon Mar 31 23:10:32 GMT 2025
PRIMARY
FDA UNII
0NG5TTM63P
Created by admin on Mon Mar 31 23:10:32 GMT 2025 , Edited by admin on Mon Mar 31 23:10:32 GMT 2025
PRIMARY
Related Record Type Details
TARGET -> AGONIST
TARGET -> INHIBITOR
ENANTIOMER -> ENANTIOMER
RACEMATE -> ENANTIOMER
Agonist of the ?. opioid receptor and inhibits serotonin reuptake.