Ans. A. Serotonin and nor-adrenaline reuptake inhibition* Tramadol differs from other traditional opioid medications in that it doesn't just act as a m-opioid agonist, but also affects monoamines by modulating the effects of neurotransmitters involved in the modulation of pain such as serotonin and norepinephrine which activate descending pain inhibitory pathways.* Tramadol's effects on serotonin and norepinephrine mimic the effects of other SNRI antidepressants such as duloxetine and venlafaxine.* Tramadol exists as a racemic mixture consisting of two pharmacologically active enantiomers that both contribute to its analgesic propey through different mechanisms and are also themselves metabolized into active metabolites: (+)-tramadol and its primary metabolite (+)-O-desmethyl-tramadol (M1) are agonists of the m opioid receptor while (+)-tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine reuptake.* These pathways are complementary and synergistic, improving tramadol's ability to modulate the perception of and response to pain.
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