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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article

Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms

Author(s): Khadga Raj, Pooja Chawla and Shamsher Singh*

Volume 18, Issue 10, 2019

Page: [758 - 768] Pages: 11

DOI: 10.2174/1871527318666191112124435

Price: $65

Abstract

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).

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

Graphical Abstract
[1]
Panahi Y, Dehcheshmeh HS, Mojtahedzadeh M, Joneidi-Jafari N, Johnston TP, Sahebkar A. Analgesic and sedative agents used in the intensive care unit: A review. J Cell Biochem 2018; 119(11): 8684-93.
[http://dx.doi.org/10.1002/jcb.27141] [PMID: 30076655]
[2]
Hamza M, Dionne RA. Mechanisms of non-opioid analgesics beyond cyclooxygenase enzyme inhibition. Curr Mol Pharmacol 2009; 2(1): 1-14.
[http://dx.doi.org/10.2174/1874467210902010001] [PMID: 19779578]
[3]
Blakemore PR, White JD. Morphine, the Proteus of organic molecules. Chem Commun (Camb) 2002; 11(11): 1159-68.
[http://dx.doi.org/10.1039/b111551k] [PMID: 12109065]
[4]
Pathan H, Williams J. Basic opioid pharmacology: An update. Br J Pain 2012; 6(1): 11-6.
[http://dx.doi.org/10.1177/2049463712438493] [PMID: 26516461]
[5]
Ghelardini C, Di Cesare Mannelli L, Bianchi E. The pharmacological basis of opioids. Clin Cases Miner Bone Metab 2015; 12(3): 219-21.
[PMID: 26811699]
[6]
Masihuddin M, Jafri MA, Siddiqui A, Chaudhary S. Traditional uses, phytochemistry and pharmacological activities of papaver somniferum with special reference of unani medicine an updated review. J Drug Deliv Ther 2018; 8: 110-4.
[http://dx.doi.org/10.22270/jddt.v8i5-s.2069]
[7]
Snyder C, Mantione K. the effects of morphine on Parkinson’srelated genes PINK1 and PARK2 medical science monitors basic research 2014; 20:: 63-9.
[8]
Mulkey MA, Hardin SR, Olson DM, Munro CL. Pathophysiology review: Seven neurotransmitters associated with delirium. Clin Nurse Spec 2018; 32(4): 195-211.
[http://dx.doi.org/10.1097/NUR.0000000000000384] [PMID: 29878931]
[9]
Sweileh WM, Shraim NY, Zyoud SH, Al-Jabi SW. Worldwide research productivity on tramadol: A bibliometric analysis. Springerplus 2016; 5(1): 1108.
[http://dx.doi.org/10.1186/s40064-016-2801-5] [PMID: 27478725]
[10]
Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet 2004; 43(13): 879-923.
[http://dx.doi.org/10.2165/00003088-200443130-00004] [PMID: 15509185]
[11]
Chelazzi C, Falsini S, Gemmi E. Pain Management in Critically Ill Patient. In: De Gaudio A, Romagnoli S, Eds; Critical Care Sedation. Germany 2018; pp. 21-34.
[http://dx.doi.org/10.1007/978-3-319-59312-8_3]
[12]
Shipton EA, Shipton EE. Shipton AJ. A review of the opioid epidemic: What do we do about it? Pain Ther 2018; 7: 1-14.
[http://dx.doi.org/10.1007/s40122-018-0096-7]
[13]
Stamer UM, Stüber F, Muders T, Musshoff F. Respiratory depression with tramadol in a patient with renal impairment and CYP2D6 gene duplication. Anesth Analg 2008; 107(3): 926-9.
[http://dx.doi.org/10.1213/ane.0b013e31817b796e] [PMID: 18713907]
[14]
Chidambaran V, Sadhasivam S, Mahmoud M. Codeine and opioid metabolism: Implications and alternatives for pediatric pain management. Curr Opin Anaesthesiol 2017; 30(3): 349-56.
[http://dx.doi.org/10.1097/ACO.0000000000000455] [PMID: 28323671]
[15]
Kumar A, Dhawan A, Kadam A, Shinde A. Targets in neurodegenerative disorders. CNS Neurol Disord Drug Targets 2018; 7(9): 696-705.
[16]
Abdel-Zaher AO, Abdel-Rahman MS, Elwasei FM. Protective effect of Nigella sativa oil against tramadol-induced tolerance and dependence in mice: Role of nitric oxide and oxidative stress. Neurotoxicology 2011; 32(6): 725-33.
[http://dx.doi.org/10.1016/j.neuro.2011.08.001] [PMID: 21855572]
[17]
Martin W. Tramadol deaths in the United Kingdom. Public Health England and UK Focal Point on Drugs 2014; pp. 1-12.
[18]
Kottayil SG, Ping JH. Intravenous administration of tramadol. US Patent 8895622B2.
[19]
Pergolizzi JV Jr, LeQuang JA, Taylor R Jr, Ossipov MH, Colucci D, Raffa RB. Designing safer analgesics: A focus on μ-opioid receptor pathways. Expert Opin Drug Discov 2018; 13(10): 965-72.
[http://dx.doi.org/10.1080/17460441.2018.1511539] [PMID: 30175624]
[20]
Lavasani H, Sheikholeslami B, Ardakani YH, Abdollahi M, Hakemi L, Rouini MR. Study of the pharmacokinetic changes of Tramadol in diabetic rats. Daru 2013; 21(1): 17.
[http://dx.doi.org/10.1186/2008-2231-21-17] [PMID: 23497674]
[21]
Lee JH, Lee CS. A randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of the extended-release tramadol hydrochloride/acetaminophen fixed-dose combination tablet for the treatment of chronic low back pain. Clin Ther 2013; 35(11): 1830-40.
[http://dx.doi.org/10.1016/j.clinthera.2013.09.017] [PMID: 24183364]
[22]
Apaydin S, Uyar M, Karabay NU, Erhan E, Yegul I, Tuglular I. The antinociceptive effect of tramadol on a model of neuropathic pain in rats. Life Sci 2000; 66(17): 1627-37.
[http://dx.doi.org/10.1016/S0024-3205(00)00482-3] [PMID: 11261592]
[23]
Lehmann KA. Tramadol in acute pain. Drugs 1997; 53(Suppl. 2): 25-33.
[http://dx.doi.org/10.2165/00003495-199700532-00007] [PMID: 9190322]
[24]
Krakowski I, Henry A. Side Effects of Nociceptive Cancer Pain Treatments in Adults. In: Dicato M, Ed; Side Effects of Medical Cancer Therapy. Springer London. 2018; pp. 595-620.
[http://dx.doi.org/10.1007/978-3-319-70253-7_19]
[25]
Predescu O, Baldini G. Opiate Medication and Routes of Delivery. In: Analgesia in Major Abdominal Surgery. Krige A, Scott M., eds.; Springer: New York. 2018; pp. 33-49.
[http://dx.doi.org/10.1007/978-3-319-94482-1_3]
[26]
Toce MS, Chai PR, Burns MM, Boyer EW. Pharmacologic treatment of opioid use disorder: A review of pharmacotherapy, adjuncts, and toxicity. J Med Toxicol 2018; 14(4): 306-22.
[http://dx.doi.org/10.1007/s13181-018-0685-1] [PMID: 30377951]
[27]
Palmer GM, Anderson BJ, Linscott DK, Paech MJ, Allegaert K. Tramadol, breast feeding and safety in the newborn. Arch Dis Child 2018; 103(12): 1110-3.
[http://dx.doi.org/10.1136/archdischild-2017-313786] [PMID: 29599166]
[28]
Sheweita SA, Almasmari AA, El-Banna SG. Tramadol-induced hepato- and nephrotoxicity in rats: Role of curcumin and gallic acid as antioxidants. PLoS One 2018; 13(8): e0202110.
[http://dx.doi.org/10.1371/journal.pone.0202110] [PMID: 30110401]
[29]
Beyaz SG, Sonbahar T, Bayar F, Erdem AF. Seizures associated with low-dose tramadol for chronic pain treatment. Anesth Essays Res 2016; 10(2): 376-8.
[http://dx.doi.org/10.4103/0259-1162.177181] [PMID: 27212778]
[30]
El-Sayed AA, Mohamed KM, Nasser AY, Button J, Holt DW. Simultaneous determination of tramadol, O-desmethyltramadol and N-desmethyltramadol in human urine by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2013; 926: 9-15.
[http://dx.doi.org/10.1016/j.jchromb.2013.02.019] [PMID: 23542669]
[31]
Cozza KL, Rein R, Wynn GH, Meyer EG. Psychopharmacology of depression as a systemic illness for primary and specialty care clinicians focus on adverse drug reactions and drug-drug interactions. Depression as a Systemic Illness 2018; 168.
[32]
Andrade A, Prasad AN. Update in Pediatric Neurology. In: Piteau S, Ed; Update in Pediatrics. Springer London. 2018; pp. 439-60.
[33]
Stafstrom CE, Carmant L. Seizures and epilepsy: An overview for neuroscientists. Cold Spring Harb Perspect Med 2015; 5(6): 1-19.
[http://dx.doi.org/10.1101/cshperspect.a022426] [PMID: 26033084]
[34]
Boostani R, Derakhshan S. Tramadol induced seizure: A 3-year study. Caspian J Intern Med 2012; 3(3): 484-7.
[PMID: 24009919]
[35]
Jovanović-Cupić V, Martinović Z, Nesić N. Seizures associated with intoxication and abuse of tramadol. Clin Toxicol (Phila) 2006; 44(2): 143-6.
[http://dx.doi.org/10.1080/1556365050014418] [PMID: 16615669]
[36]
Gholami M, Saboory E, Roshan-Milani S. Proconvulsant effects of tramadol and morphine on pentylenetetrazol-induced seizures in adult rats using different routes of administration. Epilepsy Behav 2014; 36: 90-6.
[http://dx.doi.org/10.1016/j.yebeh.2014.05.012] [PMID: 24892755]
[37]
Burtscher J, Schwarzer C. The opioid system in temporal lobe epilepsy: Functional role and therapeutic potential. Front Mol Neurosci 2017; 10: 245.
[http://dx.doi.org/10.3389/fnmol.2017.00245] [PMID: 28824375]
[38]
Lagard C, Chevillard L, Malissin I, et al. Mechanisms of tramadol-related neurotoxicity in the rat: Does diazepam/tramadol combination play a worsening role in overdose? Toxicol Appl Pharmacol 2016; 310: 108-19.
[http://dx.doi.org/10.1016/j.taap.2016.09.013] [PMID: 27641627]
[39]
Lesani A, Javadi-Paydar M, Khodadad TK, et al. Involvement of the nitric oxide pathway in the anticonvulsant effect of tramadol on pentylenetetrazole-induced seizures in mice. Epilepsy Behav 2010; 19(3): 290-5.
[http://dx.doi.org/10.1016/j.yebeh.2010.08.006] [PMID: 20880756]
[40]
Rehni AK, Singh TG, Singh N, Arora S. Tramadol-induced seizurogenic effect: A possible role of opioid-dependent histamine H1 receptor activation-linked mechanism. Naunyn Schmiedebergs Arch Pharmacol 2010; 381(1): 11-9.
[http://dx.doi.org/10.1007/s00210-009-0476-y] [PMID: 20012267]
[41]
de Oliveira Junior J.O., de Freitas MF, Bullara de Andrade C, Chacur M, Ashmawi HA. Local analgesic effect of tramadol is mediated by opioid receptors in late postoperative pain after plantar incision in rats. J Pain Res 2016; 9: 797-802.
[http://dx.doi.org/10.2147/JPR.S117674] [PMID: 27799813]
[42]
Taghaddosinejad F, Mehrpour O, Afshari R, Seghatoleslami A, Abdollahi M, Dart RC. Factors related to seizure in tramadol poisoning and its blood concentration. J Med Toxicol 2011; 7(3): 183-8.
[http://dx.doi.org/10.1007/s13181-011-0168-0] [PMID: 21735309]
[43]
Horishita T, Minami K, Uezono Y, et al. The tramadol metabolite, O-desmethyl tramadol, inhibits 5-hydroxytryptamine type 2C receptors expressed in Xenopus Oocytes. Pharmacology 2006; 77(2): 93-9.
[http://dx.doi.org/10.1159/000093179] [PMID: 16679816]
[44]
Schmidt AP, Lara DR, de Faria Maraschin J, da Silveira Perla A, Onofre Souza D. Guanosine and GMP prevent seizures induced by quinolinic acid in mice. Brain Res 2000; 864(1): 40-3.
[http://dx.doi.org/10.1016/S0006-8993(00)02106-5] [PMID: 10793184]
[45]
Pearson-Smith JN, Patel M. metabolic dysfunction and oxidative stress in epilepsy. Int J Mol Sci 2017; 18(11): 1-13.
[http://dx.doi.org/10.3390/ijms18112365] [PMID: 29117123]
[46]
Ravizza T, Vezzani A. Pharmacological targeting of brain inflammation in epilepsy: Therapeutic perspectives from experimental and clinical studies. Epilepsia Open 2018; 3(Suppl Suppl 2): 133-42.
[http://dx.doi.org/10.1002/epi4.12242] [PMID: 30564772]
[47]
Mégarbane B, Lagard C, Chevillard L. Tramadol: Distinguishing the pathophysiology of serotonin syndrome and seizures. Am J Med 2018; 131(11): e487.
[http://dx.doi.org/10.1016/j.amjmed.2018.07.005] [PMID: 30392647]
[48]
Sosna J, Philipp S, Albay R III, et al. Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease. Mol Neurodegener 2018; 13(1): 11.
[http://dx.doi.org/10.1186/s13024-018-0244-x] [PMID: 29490706]
[49]
Hussain G, Zhang L, Rasul A, et al. Role of plant-derived flavonoids and their mechanism in attenuation of Alzheimer’s and Parkinson’s diseases: An update of recent data. Molecules 2018; 23(4): 1-26.
[http://dx.doi.org/10.3390/molecules23040814] [PMID: 29614843]
[50]
Singh A, Hasan A, Tiwari S, Pandey LM. Therapeutic advancement in Alzheimer disease: New hopes on the horizon. CNS Neurol Disord Drug Targets 2018; 17: 571-89.
[51]
Shi Y, Wang Y, Wei H. Dantrolene: From malignant hyperthermia to Alzheimer’s disease. CNS Neurol Disord Drug Targets 2019. [Epub ahead of print].
[52]
Wang K, Sun W, Zhang L, et al. Oleanolic acid ameliorates Aβ25-35 injection-induced memory deficit in Alzheimer’s disease model rats by maintaining synaptic plasticity. CNS Neurol Disord Drug Targets 2018; 17: 389-99.
[http://dx.doi.org/10.2174/1871527317666180525113109]
[53]
Bais S, Kumari R, Prashar Y. Ameliorative effect of trans-sinapic acid and its protective role in cerebral hypoxia in aluminium chloride induced dementia of Alzheimer’s type. CNS Neurol Disord Drug Targets 2018; 17(2): 144-54.
[http://dx.doi.org/10.2174/1871527317666180309130912]
[54]
Hosseini-Sharifabad A, Rabbani M, Sharifzadeh M, Bagheri N. Acute and chronic tramadol administration impair spatial memory in rat. Res Pharm Sci 2016; 11(1): 49-57.
[PMID: 27051432]
[55]
Izquierdo I, Bevilaqua LR, Rossato JI, Bonini JS, Medina JH, Cammarota M. Different molecular cascades in different sites of the brain control memory consolidation. Trends Neurosci 2006; 29(9): 496-505.
[http://dx.doi.org/10.1016/j.tins.2006.07.005] [PMID: 16872686]
[56]
Abel T, Nguyen PV. Regulation of hippocampus-dependent memory by cyclic AMP-dependent protein kinase. Prog Brain Res In: 2008; 169: : pp. 97-115.
[http://dx.doi.org/10.1016/S0079-6123(07)00006-4] [PMID: 18394470]
[57]
Baghishani F, Mohammadipour A, Hosseinzadeh H, Hosseini M, Ebrahimzadeh-Bideskan A. The effects of tramadol administration on hippocampal cell apoptosis, learning and memory in adult rats and neuroprotective effects of crocin. Metab Brain Dis 2018; 33(3): 907-16.
[http://dx.doi.org/10.1007/s11011-018-0194-6] [PMID: 29470767]
[58]
Gupta P, Sil S, Ghosh R, Ghosh A, Ghosh T. Intracerebroventricular Aβ-Induced neuroinflammation alters peripheral immune responses in rats. J Mol Neurosci 2018; 66(4): 572-86.
[http://dx.doi.org/10.1007/s12031-018-1189-9] [PMID: 30377887]
[59]
Ghoneim FM, Khalaf HA, Elsamanoudy AZ, Helaly AN. Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study. Int J Clin Exp Pathol 2014; 7(11): 7323-41.
[PMID: 25550769]
[60]
Mohamed TM, Ghaffar HMA, El Husseiny RM. Effects of tramadol, clonazepam, and their combination on brain mitochondrial complexes. Toxicol Ind Health 2015; 31(12): 1325-33.
[http://dx.doi.org/10.1177/0748233713491814] [PMID: 23843224]
[61]
Mehdizadeh H, Pourahmad J, Taghizadeh G, et al. Mitochondrial impairments contribute to spatial learning and memory dysfunction induced by chronic tramadol administration in rat: Protective effect of physical exercise. Prog Neuropsychopharmacol Biol Psychiatry 2017; 79(Pt B): 426-33.
[http://dx.doi.org/10.1016/j.pnpbp.2017.07.022] [PMID: 28757160]
[62]
Zhai L, Zhang P, Sun RY, Liu XY, Liu WG, Guo XL. Cytoprotective effects of CSTMP, a novel stilbene derivative, against H2O2-induced oxidative stress in human endothelial cells. Pharmacol Rep 2011; 63(6): 1469-80.
[http://dx.doi.org/10.1016/S1734-1140(11)70711-3] [PMID: 22358095]
[63]
Hassanian-Moghaddam H, Farajidana H, Sarjami S, Owliaey H. Tramadol-induced apnea. Am J Emerg Med 2013; 31(1): 26-31.
[http://dx.doi.org/10.1016/j.ajem.2012.05.013] [PMID: 22809771]
[64]
Costa JT, Mele M, Baptista MS, et al. Gephyrin cleavage in in vitro brain ischemia decreases GABAA receptor clustering and contributes to neuronal death. Mol Neurobiol 2016; 53(6): 3513-27.
[http://dx.doi.org/10.1007/s12035-015-9283-2] [PMID: 26093381]
[65]
Zeng LH, Ouyang Y, Gazit V, et al. Abnormal glutamate homeostasis and impaired synaptic plasticity and learning in a mouse model of tuberous sclerosis complex. Neurobiol Dis 2007; 28(2): 184-96.
[http://dx.doi.org/10.1016/j.nbd.2007.07.015] [PMID: 17714952]
[66]
Bagheri-Abassi F, Alavi H, Mohammadipour A, Motejaded F, Ebrahimzadeh-Bideskan A. The effect of silver nanoparticles on apoptosis and dark neuron production in rat hippocampus. Iran J Basic Med Sci 2015; 18(7): 644-8.
[PMID: 26351553]
[67]
Nedi T, White PJ, Coupar IM, Irving HR. Effect of the 5-HT4 receptor agonist tegaserod on the expression of GRK2 and GRK6 in the rat gastrointestinal tract. BMC Res Notes 2018; 11(1): 362.
[http://dx.doi.org/10.1186/s13104-018-3495-2] [PMID: 29884229]
[68]
Baldo BA. Opioid analgesic drugs and serotonin toxicity (syndrome): Mechanisms, animal models, and links to clinical effects. Arch Toxicol 2018; 92(8): 2457-73.
[http://dx.doi.org/10.1007/s00204-018-2244-6] [PMID: 29916050]
[69]
Haage P, Kronstrand R, Josefsson M, et al. Enantioselective pharmacokinetics of tramadol and its three main metabolites; impact of CYP2D6, CYP2B6, and CYP3A4 genotype. Pharmacol Res Perspect 2018; 6(4): e00419.
[http://dx.doi.org/10.1002/prp2.419] [PMID: 29992026]
[70]
Haufroid V, Hantson P. CYP2D6 genetic polymorphisms and their relevance for poisoning due to amfetamines, opioid analgesics and antidepressants. Clin Toxicol (Phila) 2015; 53(6): 501-10.
[http://dx.doi.org/10.3109/15563650.2015.1049355] [PMID: 25998998]
[71]
Hicks JK, Bishop JR, Sangkuhl K, et al. LLerena A, Skaar TC. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharmacol Ther 2015; 98(2): 127-34.
[http://dx.doi.org/10.1002/cpt.147] [PMID: 25974703]
[72]
Beakley BD, Kaye AM, Kaye AD. Tramadol, pharmacology, side effects, and serotonin syndrome: A review. Pain Physician 2015; 18(4): 395-400.
[PMID: 26218943]
[73]
Rosenblatt K. Neuroleptic Malignant Syndrome. In: Hyzy R, Ed;Evidence-Based Critical Care. Springer London. 2017; pp. 343-53.
[http://dx.doi.org/10.1007/978-3-319-43341-7_39]
[74]
Rickli A, Liakoni E, Hoener MC, Liechti ME. Opioid-induced inhibition of the human 5-HT and noradrenaline transporters in vitro: Link to clinical reports of serotonin syndrome. Br J Pharmacol 2018; 175(3): 532-43.
[http://dx.doi.org/10.1111/bph.14105] [PMID: 29210063]
[75]
Haleem DJ, Nawaz S, Salman T. Dopamine and serotonin metabolism associated with morphine reward and its inhibition with buspirone: A study in the rat striatum. Pharmacol Biochem Behav 2018; 170: 71-8.
[http://dx.doi.org/10.1016/j.pbb.2018.05.010] [PMID: 29782941]
[76]
Klinge M, Coppler T, Liebschutz JM, et al. The assessment and management of pain in cirrhosis. Curr Hepatol Rep 2018; 17(1): 42-51.
[http://dx.doi.org/10.1007/s11901-018-0389-7] [PMID: 29552453]
[77]
Fatima A, Jyoti S, Siddique YH. Models of Parkinson’s disease with special emphasis on Drosophila melanogaster. CNS Neurol Disord Drug Targets 2018; 17(10): 757-66.
[http://dx.doi.org/10.2174/1871527317666180820164250]
[78]
Askar MH, Hussein AM, Al-Basiony SF, et al. Effects of exercise and ferulic acid on alpha synuclein and neuroprotective heat shock protein 70 in an experimental model of Parkinsonism disease. CNS Neurol Disord Drug Targets 2019; 18(2): 156-69.
[http://dx.doi.org/10.2174/1871527317666180816095707]
[79]
Ayano G. Dopamine: Receptors, functions, synthesis, pathways, locations and mental disorders: Review of literatures. J Ment Disord and Treatment 2016; 2: 2-5.
[http://dx.doi.org/10.4172/2471-271X.1000120]
[80]
Abushouk AI, Negida A, Elshenawy RA, et al. C-Abl inhibition; a novel therapeutic target for Parkinson’s disease. CNS Neurol Disord Targets 2018; 17(1): 14-21.
[81]
Brotini S, Schievano C, Guidi L. Ultra-micronized palmitoylethanolamide: An efficacious adjuvant therapy for Parkinson’s disease. CNS Neurol Disord Drug Targets 2017; 16(6): 705-13.
[http://dx.doi.org/10.2174/1871527316666170321124949]
[82]
Coneglian de Farias C, Maes M, Landucci Bonifacio K, et al. Parkinson’s disease is accompanied by intertwined alterations in iron metabolism and activated immune-inflammatory and oxidative stress pathways. CNS Neurol Disord Drug Targets 2017; 16(4): 484-91.
[83]
Hassanian-Moghaddam H, Farnaghi F, Rahimi M. Tramadol overdose and apnea in hospitalized children, a review of 20 cases. Res Pharm Sci 2015; 10(6): 544-52.
[PMID: 26779274]
[84]
Hara K, Minami K, Sata T. The effects of tramadol and its metabolite on glycine, γ-aminobutyric acidA, and N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Anesth Analg 2005; 100(5): 1400-5.
[http://dx.doi.org/10.1213/01.ANE.0000150961.24747.98] [PMID: 15845694]
[85]
Barber J. Examining the use of tramadol hydrochloride as an antidepressant. Exp Clin Psychopharmacol 2011; 19(2): 123-30.
[http://dx.doi.org/10.1037/a0022721] [PMID: 21463069]
[86]
El-Baky AEA, Hafez MM. NOS expression in oxidative stress, neurodegeneration and male infertility induced by the abuse of tramadol. Biochem Pharmacol 2017; 6: 1-6.
[87]
Louis ED, Frucht SJ, Rios E. Intention tremor in essential tremor: Prevalence and association with disease duration. Mov Disord 2009; 24(4): 626-7.
[http://dx.doi.org/10.1002/mds.22370] [PMID: 19185016]
[88]
Mellor K, Ahmed A, Thomson A. Tramadol hydrochloride use and acute deterioration in Parkinson’s disease tremor. Mov Disord 2009; 24(4): 622-3.
[http://dx.doi.org/10.1002/mds.22449] [PMID: 19185012]
[89]
Vilariño-Güell C, Ross OA, Soto AI, et al. Reported mutations in GIGYF2 are not a common cause of Parkinson’s disease. Mov Disord 2009; 24(4): 619-20.
[http://dx.doi.org/10.1002/mds.22451] [PMID: 19133664]
[90]
Singh R. Tramadol-induced parkinsonism: A case report of a 75-year-old woman. J Basic Clin Physiol Pharmacol 2018; 30(2): 275-8.
[http://dx.doi.org/10.1515/jbcpp-2018-0113] [PMID: 30447142]
[91]
Ugoya SO, Agaba EI, Daniyam CA. Parkinsonism caused by adverse drug reactions: A case series. J Med Case Reports 2011; 5: 105.
[http://dx.doi.org/10.1186/1752-1947-5-105] [PMID: 21410947]
[92]
Steele A. Opioid use and depression in chronic pelvic pain. Obstet Gynecol Clin North Am 2014; 41(3): 491-501.
[http://dx.doi.org/10.1016/j.ogc.2014.04.005] [PMID: 25155127]
[93]
Schumacher MA, Basbaum AI, Way WL. Opioid agonists & antagonists. In: Basic and clinical pharmacology. Katzung BG, Trevor AJ. eds, McGraw-Hill Education: New York, . 2009; pp. 531-52.

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