Tramadol is a centrally acting synthetic opioid agonist and SNRI used for the management of moderate to severe pain in adults. It is structurally related to codeine and morphine. It main mechanism of action is on mu-opioid receptors and SNRIs, but it also known to effect pain modulators such as adrenoreceptors, neurokinin receptors, voltage-gated sodium channels, capsaicin receptors, muscarinic receptors (M1 and M3), NMDA receptors, adenosine receptors, and nicotinic acetylcholine receptors. Tramadol diffuses across the blood-brain barrier after being absorbed by the intestine. It then inhibits NMDA receptors in the brain. This prevents glutamate from binding to NMDA receptors, which prevents calcium from entering the postsynaptic neuron which leads to hyperpolarization.

Tramadol NMDA Antagonist Pathway References