Neuroscience Division, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab 142001, India.
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab 142001, India.
CNS Neurol Disord Drug Targets. 2019;18(10):758-768. doi: 10.2174/1871527318666191112124435.
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).
曲马多是一种合成的可待因类似物，用于治疗中重度疼痛，据报道具有神经毒性潜力。与其他阿片类镇痛药相比，曲马多在治疗剂量下不会引起主要副作用，并且可用于治疗焦虑和抑郁等神经问题。长期使用曲马多与各种神经障碍有关，如癫痫、血清素综合征、阿尔茨海默病和帕金森病。曲马多通过抑制一氧化氮、血清素再摄取以及对 GABA 受体的抑制作用产生癫痫。大量摄入曲马多会通过提高脂质过氧化和自由基水平来改变氧化还原平衡，导致神经毒性并产生神经行为缺陷。在阿尔茨海默病进展过程中，细胞内信号分子如 cGMP、cAMP、PKC 和 PKA 的水平降低会影响学习和记忆。曲马多在药理学上产生的作用类似于选择性 5-羟色胺再摄取抑制剂 (SSRIs)，增加了 5-羟色胺的浓度，从而导致血清素综合征。此外，曲马多还抑制中枢神经系统中的 GABA A 受体，这已被证明会干扰多巴胺的合成和释放，导致运动症状。多巴胺水平降低可能导致运动迟缓症和震颤，这是帕金森病 (PD) 的主要运动异常。
