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As a racemic mixture with a weak affinity for the μ-opioid receptor (approximately 1 6000th that of morphine; Gutstein & Akil, 2006). The (+)-enantiomer is approximately four times more potent than the (-)-enantiomer in terms of μ-opioid receptor affinity and 5-HT reuptake, whereas the (-)-enantiomer is responsible for noradrenaline reuptake effects (Shipton, 2000). These actions appear to produce a synergistic analgesic effect, with (+)-tramadol exhibiting 10-fold higher analgesic activity than (-)-tramadol (Goeringer et al., 1997). The serotonergic-modulating properties of tramadol give tramadol the potential to interact with other serotonergic agents. There is an increased risk of serotonin syndrome when tramadol is taken in combination with serotonin reuptake inhibitors (e.g., SSRIs) or with use of a light box, since these agents not only potentiate the effect of 5-HT but also inhibit tramadol metabolism. Tramadol is also thought to have some NMDA-type antagonist effects, which has given it a potential application in neuropathic pain states. The overall analgesic profile of tramadol supports intermediate pain especially chronic states, is slightly less effective for acute pain than hydrocodone, but more effective than codeine. It has a dosage ceiling similar to codeine, a risk of seizures when overdosed, and a relatively long half-life making its potential for abuse relatively low amongst intermediate strength analgesics. edit Metabolism Tramadol undergoes hepatic metabolism via the cytochrome P450 isozyme CYP2D6, being O- and N-demethylated to five different meta Buy cancer

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