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Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms

[ Vol. 18 , Issue. 10 ]


Khadga Raj, Pooja Chawla and Shamsher Singh*   Pages 758 - 768 ( 11 )


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).


Tramadol, Parkinson’s disease, Alzheimer’s disease, serotonin syndrome, seizure, central nervous system, oxidative stress, cytochrome, electroencephalogram, naloxone, rigidity, pathological, mitochondrial complexes.


Neuroscience Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab 142001, Neuroscience Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001

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