Tramadol hydrochloride (trademarked as Conzip, Ryzolt, Ultracet, Ultram in the USA,Ralivia and Zytram XL in Canada) is a centrally acting syntheticanalgesic used to treat moderate to moderately-severe pain. The drug has a wide range of applications, including treatment of rheumatoid arthritis,restless legs syndrome and fibromyalgia. It was launched and marketed asTramal by the German pharmaceutical company Grünenthal GmbH in 1977.[1][2]
Tramadol is a very weak μ-opioid receptor agonist, induces serotoninrelease, and inhibits the reuptake of norepinephrine.[3][4] Tramadol is converted to O-desmethyltramadol, a significantly more potent μ-opioid agonist. The opioid agonistic effect of tramadol and its major metabolite(s) is almost exclusively mediated by such μ-opioid receptors. This further distinguishes tramadol from opioids in general (including morphine), which do not possess tramadol's degree of receptor subtype selectivity and which are much stronger opiate-receptor agonists. Similarly, the habituating properties of tramadol (such as they are) are arguably mainly due to μ-opioid agonism with contributions from serotonergic and noradrenergic effects.
Tramadol is used similarly to codeine, to treat moderate to moderately severe pain.[5] Pharmacologically, Tramadol is similar to levorphanol (albeit with much lower μ-agonism), as both agents are also NMDA-antagonists with SNRI activity. Dextropropoxyphene (Darvon) & M1-like moleculetapentadol (Nucynta, a new synthetic atypical opioid made to mimic the agonistic properties of tramadol's metabolite, M1(O-Desmethyltramadol)) also have similar activities. Tramadol is also molecularly similar tovenlafaxine (Effexor) and has similar SNRI effects, with antinociceptive effects. It has been suggested that tramadol could be effective for alleviating symptoms of depression, anxiety, and phobias because of its action on the noradrenergic and serotonergic systems, such as its "atypical" opioid activity. However, health professionals have not endorsed its use for these disorders,[8][9] claiming it may be used as a unique treatment (only when other treatments failed), and must be used under the control of a psychiatrist.
In May 2009, the United States Food and Drug Administration issued a Warning Letter to Johnson & Johnson, alleging that a promotional website commissioned by the manufacturer had "overstated the efficacy" of the drug, and "minimized the serious risks".[12]The company which produced it, the German pharmaceutical company Grünenthal GmbH, were alleged to be guilty of "minimizing" the habituating nature of the drug, although it showed little abuse liability in preliminary tests.[citation needed] The 2010 Physicians Desk Reference contains several warnings from the manufacturer, which were not present in prior years. The warnings include stronger language regarding the habituating potential of tramadol, the possibility of difficulty breathing while on the medication, a new list of more serious side effects, and a notice that tramadol is not to be used in place of opiate medications for addicts. Tramadol is also not to be used in efforts to wean addict patients from opiate drugs, nor to be used to manage long-term opiate addiction.
