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Tramadol belongs to the anisoles, a subclass of phenol ethers within the organic compounds. It is an exogenous solid with the formula C16H25NO2 and an average molecular weight of 263.38 g/mol. As a drug (PMC6006277 ), it is used as an analgesic, opioid analgesic, and antitussive (PMC2663660 , PMC7307949 ). It is used in the treatment of pain (PMC6942774 ) and chronic pain (PMC2663660 , PMC8035696 ).
Biologically, tramadol acts as a delta-opioid receptor agonist, kappa-opioid receptor agonist, mu-opioid receptor agonist, serotonin uptake inhibitor, serotonergic antagonist, adrenergic uptake inhibitor, nicotinic antagonist, muscarinic antagonist, and NMDA receptor antagonist (PMC2663660 , PMC7307949 ). It also functions as a capsaicin receptor antagonist (PMC2663660 , PMC7307949 ). Recorded protein targets include the mu-type opioid receptor (OPRM1), sodium-dependent noradrenaline transporter (SLC6A2), 5-hydroxytryptamine receptor 2C (HTR2C), and kappa-type opioid receptor (OPRK1), among others. 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 inhibiting the release of nociceptive neurotransmitters.
Health effects associated with tramadol include nausea, dizziness, vomiting, and headache (PMC9392978 ), as well as seizure, bradycardia, tachycardia, hypotension, and coma (PMC8035696 ). It is also associated with a decrease in hyperprolactinemia (PMC7807371 ). Exposure routes include oral, inhalation, and topical.
plant metabolite ?Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms
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.
No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk Level
Not Available
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)
A disorder characterized by a sensation of marked discomfort in various parts of the head, not confined to the area of distribution of any nerve. (NCI CTCAE)
A disorder characterized by a sensation of marked discomfort in various parts of the head, not confined to the area of distribution of any nerve. (NCI CTCAE)
A disorder characterized by a sensation of marked discomfort in various parts of the head, not confined to the area of distribution of any nerve. (NCI CTCAE)
Hyperprolactinemia is the abnormal elevation of serum prolactin level. Prolactin is a peptide hormone produced by the anterior pituitary gland that is primarily associated with lactation and plays a vital role in breast development during pregnancy. Hyperprolactinaemia may cause galactorrhea (production and spontaneous flow of breast milk), infertility, and disruptions in the normal menstrual period in women; and hypogonadism, infertility and erectile dysfunction in men. Hyperprolactinemia can be caused by prolactinoma (a type of pituitary adenoma)., which accounts for 40% of pituitary cancers. Other causes include chronic kidney failure, hypothyroidism, bronchogenic carcinoma and sarcoidosis. Some women with polycystic ovary syndrome may have mildly-elevated prolactin levels.
A state of profound unconsciousness associated with markedly depressed cerebral activity. Causes include central nervous system damage, intoxication, and metabolic abnormalities.
Indoor air?Indoor air can be a significant reservoir for synthetic chemical contaminants, which often originate from various sources within enclosed environments.
Drinking water?Drinking water can be a medium for synthetic chemical contamination, often originating from various industrial processes and agricultural practices.
Effluent?Effluent refers to liquid waste or sewage that is discharged into the environment, typically resulting from industrial processes, municipal wastewater treatment, or agricultural runoff.
WWTP influent?WWTP influent refers to the raw wastewater entering a wastewater treatment plant, which can contain a complex mixture of pollutants, including synthetic chemicals.
Fencing?Fencing materials, particularly those used in construction and landscaping, can be a source of synthetic chemical contamination due to the treatments and coatings applied for durability and weather resistance.
Ladders?Ladders, commonly used in various construction and maintenance activities, can become a source of synthetic chemical contamination due to the materials and coatings applied during their manufacture and use.
Tents Or Canopies?Tents and canopies used in various applications can be a source of synthetic chemical contamination primarily due to the materials from which they are made.
Antennas?Antennas, commonly used in communication technologies, can be a source of synthetic chemical contamination through the materials and coatings used in their construction.
Conductors Or Conductive Bodies Characterised By The Conductive Materials?Conductors, or conductive bodies, are materials that allow the flow of electrical current, typically made from metals such as copper, aluminum, or silver.
Electric Switches?Electric switches, integral components in numerous devices, can be a source of synthetic chemical contamination due to the materials and manufacturing processes involved in their production.
Electrically Stimulated Smoking Devices?Electrically stimulated smoking devices, commonly known as e-cigarettes or vape pens, utilize electrical components to heat a liquid solution, often containing nicotine, flavorings, and other additives, to produce an aerosol for inhalation.
Electrodes?Electrodes, used in various electrical and electronic applications, can be a source of synthetic chemical contamination due to the materials from which they are constructed and the processes involved in their manufacturing.
Emergency Protective Devices?Emergency protective devices, such as circuit breakers and surge protectors, are essential components in electrical systems designed to prevent damage from overcurrent and surges.
Hybrid Capacitors?Hybrid capacitors are energy storage devices that combine the properties of electrolytic and supercapacitors, utilizing a combination of electrochemical principles to achieve higher energy density and power density.
Television Systems?Television systems can be a source of synthetic chemical contamination due to the various materials and components used in their manufacture and operation.
Food Preservation?Food preservation often involves the use of synthetic chemicals, such as preservatives, flavor enhancers, and color additives, to extend shelf life and enhance the sensory qualities of food products.
Preparation Of Wine Or Sparkling Wine?The preparation of wine or sparkling wine involves various stages, including fermentation, aging, and bottling, which can introduce potential sources of synthetic chemical contamination.
Bleaching Agents?Bleaching agents are chemical substances used to whiten or lighten materials, often employed in various cleaning products for their stain removal and disinfecting properties.
Non Electric Simulated Smoking Devices?Non-electric simulated smoking devices, often designed to mimic the experience of smoking without combustion, can be sources of synthetic chemical contamination due to the materials and chemicals used in their construction and operation.
Other Smoking Requisites?Other smoking requisites, including items such as lighters, matches, and rolling papers, can introduce synthetic chemical contamination through various components and additives.
Perfumes Within Detergents And Soaps?Perfumes within detergents and soaps are synthetic fragrance compounds added to enhance the sensory experience of cleaning products.
Tobacco Smoke Filters?Tobacco smoke filters are designed to reduce the inhalation of harmful substances in cigarette smoke, including tar and other particulate matter.
Manufacture Preparation Of Tobacco Products?The manufacture and preparation of tobacco products involve various processes that can result in the introduction of synthetic chemicals into the environment.
Paper Making Machines?Paper making machines utilize various synthetic chemicals throughout the production process, including additives, coatings, and bleaching agents.
Molluscicides?Molluscicides are synthetic chemicals specifically designed to control and eliminate mollusks, such as snails and slugs, which can be detrimental to crops and agricultural productivity.
Nematocides?Nematocides are synthetic chemicals specifically designed to control nematodes, which are microscopic roundworms that can cause significant damage to crops and plants.
Aftersun Products?Aftersun products are designed to soothe and hydrate the skin after sun exposure, often containing various synthetic chemicals such as emollients, preservatives, and fragrances.
Anti Perspirants Or Body Deoderants?Antiperspirants and body deodorants commonly contain synthetic chemicals such as aluminum compounds, parabens, and synthetic fragrances.
Eye Makeup Products?Eye makeup products, including mascaras, eyeliners, and eyeshadows, often contain a variety of synthetic chemicals such as pigments, preservatives, and film-forming agents.
Lip Care Products?Lip care products, including lipsticks, balms, and glosses, often contain a variety of synthetic chemicals such as parabens, phthalates, and synthetic fragrances.
Lip Makeup Products?Lip makeup products, such as lipsticks, lip glosses, and lip liners, often contain a variety of synthetic chemicals, including pigments, preservatives, and emollients.
Toys?Toys, particularly those made from synthetic materials such as plastics, can be a source of chemical contamination due to the presence of various additives and compounds used in their production.
Buttons?Buttons, often made from synthetic materials such as polyester, nylon, or polycarbonate, can be a source of synthetic chemical contamination during their production, use, and disposal.
Footwear?Footwear production often involves the use of various synthetic chemicals, such as adhesives, dyes, and treatments, which can contribute to environmental contamination.
Headwear?Headwear made from synthetic materials often incorporates chemicals used in the manufacturing and finishing processes, such as dyes, flame retardants, and water repellents.
Pins Clothes?Pins Clothes can serve as a potential source of synthetic chemical contamination due to the use of various synthetic fibers and finishes in textile production.
Purses Luggage Hand Bags?Purses, luggage, and handbags are often manufactured using synthetic materials such as polyvinyl chloride (PVC), polyurethane, and various types of nylon.
Purses Money Bags Wallets?Purses, money bags, and wallets are often manufactured using synthetic materials, including plastics, polyurethanes, and various treated fabrics.
Snap Fasteners?Snap fasteners, commonly used in clothing and upholstery, can be made from various synthetic materials, including plastics and metal alloys.
Transfer Printing?Transfer printing is a process used to apply designs and patterns onto various substrates, commonly utilizing synthetic dyes and inks that can contain hazardous chemicals.
Yarns Or Threads?Yarns or threads used in textiles can be a source of synthetic chemical contamination due to the production processes and treatments they undergo.
Airplanes And Helicopters?Airplanes and helicopters are significant sources of synthetic chemical contamination primarily through the use of aviation fuels, lubricants, and de-icing agents.
Nitrogenous Fertilisers?Nitrogenous fertilizers are synthetic chemical compounds primarily used to enhance plant growth by supplying essential nitrogen, a crucial nutrient for photosynthesis and protein synthesis.
Glass Coatings?Glass coatings are synthetic chemical formulations applied to glass surfaces to enhance properties such as durability, UV resistance, and aesthetic appeal.
Silica Glass?Silica glass, primarily composed of silicon dioxide (SiO2), is widely used in various applications, including windows, glass facades, and insulation materials.
Treatment Of Milk Or Cream?The treatment of milk or cream involves various processes such as pasteurization, homogenization, and the addition of preservatives to enhance shelf life and safety.
Nanotechnology?Nanotechnology involves the manipulation of materials at the molecular or atomic level, typically within the range of 1 to 100 nanometers.
Mining Or Quarrying?Mining and quarrying operations can lead to synthetic chemical contamination through the release of various pollutants associated with the extraction and processing of minerals.
Sludge Treatment?Sludge treatment involves the processing of waste materials generated from wastewater treatment plants, which often contain a variety of organic and inorganic substances.
Water, Wastewater, & Sewage Treatment?Water, wastewater, and sewage treatment processes are critical for managing and mitigating pollutants in water systems.
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.
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.
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.
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.
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.
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]
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]
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]
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]
Matthiesen T, Wohrmann T, Coogan TP, Uragg H: The experimental toxicology of tramadol: an overview. Toxicol Lett. 1998 Mar 16;95(1):63-71. [PubMed: 9650647]
