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Missing image
Molecular structure of tramadol



Empirical formula C16H25NO2
Molecular weight 263.4
Bioavailability (Oral) 68-72%
Metabolism hepatic
Half life 5-7 hours
Excretion renal
Pregnancy category C (Australia)
Legal status Schedule 4 (Australia)
Routes of administration oral, IV, IM

Tramadol is an opioid used as an analgesic for treating moderate to severe pain. It is a synthetic agent, unrelated to other opioids, and appears to have actions on the GABAergic, noradrenergic and serotonergic systems. Tramadol was developed by the German pharmaceutical company Grünenthal GmbH and marketed under the trade name Tramal®. Grünenthal has also cross licensed the drug to many other pharmaceutical companies that market it under various names, some of which are listed below.

Tramadol is available in both intravenous and oral preparations. It is usually marketed as the hydrochloride salt (tramadol hydrochloride). Dosages vary depending on the degree of pain experienced by the patient, and should be decided on the basis of need by the prescriber.


Mechanism of action

The mechanism of action of tramadol has yet to be fully elucidated, but it is believed to work through modulation of the GABAergic, noradrenergic and serotonergic systems. Tramadol [and its metabolite, known as M1] have been found to bind to μ-opioid receptors (thus exerting its effect on GABAergic transmission), and to inhibit reuptake of 5-HT and noradrenaline. The second mechanism is believed to contribute since the analgesic effects of tramadol are not fully antagonised by the μ-opioid receptor antagonist naloxone.

Although irrelevant to its mechanism of action, tramadol, unlike morphine, has not been found to induce histamine release.

The serotonergic modulating properties of tramadol mean that it has the potential to interact with other serotonergic agents. There is an increased risk of serotonin syndrome when tramadol is taken in combination with reuptake inhibitors (e.g. SSRIs), agents that potentiate the effect of 5-HT (e.g., MAOIs), or 5-HT agonists.


Some controversy exists regarding the dependence liability of tramadol. Grünenthal has promoted it as an opioid with "little" risk of dependence, claiming little evidence of such dependence in their clinical trials. They offer the theory that since the M1 metabolite is the principal agonist at μ-opioid receptors, the delayed agonist activity reduces dependence liability.

Despite these claims it is apparent, in community practice, that dependence does occur to this agent. This would be expected since analgesic and dependence effects are mediated by the same μ-opioid receptor. However, this dependence liability is considered relatively low by health authorities, such that tramadol is classified as a Schedule 4 [Prescription Only Medicine] in Australia, rather than as a Schedule 8 [Controlled Drug] like other opioids (Rossi, 2004 ).

Proprietary preparations

Grünenthal, which still owns the patent to tramadol, has cross-licensed the agent to various pharmaceutical companies internationally. Thus tramadol is marketed under many trade names including: Contramal, Crispin, Nobligan, Siverol, Tiparol, Toplagic, Tradolan, Tralgit, Tramacet, Tramadin, Ultram, Zamadol and Zydol.


  • Rossi, S (Ed.) (2004). Australian Medicines Handbook 2004 (AMH). Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.

Analgesics edit (

{Paracetamol (acetaminophen) } {Tetrahydrocannabinol} {Cannabinoids} {Ketamine}

NSAIDs edit (

{Aspirin} {Celecoxib} {Diclofenac} {Ibuprofen} {Ketoprofen} {Ketorolac} {Naproxen} {Rofecoxib} {Indomethacin}

Opioids edit (

{Alfentanil} {Buprenorphine} {Carfentanil} {Codeine} {Codeinone} {Dextropropoxyphene} {Dihydrocodeine} {Endorphin} {Fentanyl} {Heroin} {Hydrocodone} {Hydromorphone} {Methadone} {Morphine} {Morphinone} {Oxycodone} {Oxymorphone} {Pethidine} {Remifentanil} {Sufentanil} {Tramadol}


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