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Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity
and is reported to have neurotoxic potential. At therapeutic dose, tramadol does not cause major side
effects in comparison to other opioid analgesics, and is useful for the management of neurological
problems like anxiety and depression. Long term utilization of tramadol is associated with various neurological
disorders like seizures, serotonin syndrome, Alzheimer’s disease and Parkinson’s disease.
Tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake and inhibitory effects
on GABA receptors. Extensive tramadol intake alters redox balance through elevating lipid peroxidation
and free radical leading to neurotoxicity and produces neurobehavioral deficits. During Alzheimer’s
disease progression, low level of intracellular signalling molecules like cGMP, cAMP, PKC
and PKA affect both learning and memory. Pharmacologically tramadol produces actions similar to Selective
Serotonin Reuptake Inhibitors (SSRIs), increasing the concentration of serotonin, which causes
serotonin syndrome. In addition, tramadol also inhibits GABAA receptors in the CNS has been evidenced
to interfere with dopamine synthesis and release, responsible for motor symptoms. The reduced
level of dopamine may produce bradykinesia and tremors which are chief motor abnormalities in Parkinson’s
Disease (PD).
Characterization of a Cul9–Parkin double knockout mouse model for Parkinson’s disease
