Tramadol

Tramadol is a weak opioid analgesic. Tramadol and its active metabolite O-desmethyltramadol exert mild effects on the mu-opioid receptor in the central nervous system. Through Gi/o proteins, they inhibit adenylyl cyclase, reduce cAMP production, and thereby suppress presynaptic voltage-gated Ca2+ channels, preventing calcium entry into the cell and reducing the release of pain-related neurotransmitters such as glutamate and substance P, which decreases pain signal transmission. They also activate postsynaptic potassium channels, causing neuronal membrane hyperpolarization and lowering the probability of neuronal firing. In addition, tramadol inhibits the norepinephrine transporter and the serotonin transporter, increasing synaptic concentrations of norepinephrine and serotonin and enhancing the actions of both neurotransmitters.