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Motor and non-motor symptoms, drugs, and their mode of action in Parkinson’s disease (PD): a review

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Abstract

Parkinson’s disease is second most common neurodegenerative disorder neurological illness that primarily affects patients in their later years of life. Specific neurons in the brain begin to malfunction resulting in a loss of a substance called dopamine which is characterized by the accumulation of α-synuclein aggregates within cells, forming structures known as Lewy bodies and Lewy neurites. It is affecting more than 1% of people worldwide (aged 65 and above) and is expected to increase in prevalence by 2030. Muscle rigidity, tremor, and unresponsiveness of motion are some of the motor signs of this condition, and on another hand pain, despair, and anxiety are some examples of non-motor symptoms. Levodopa, pramipexole, ropinirole, alprazolam, benztropine, trihexyphenidyl, and many more drugs are used to treat symptoms of Parkinson’s disease. Among them, the most common surgical symptomatic treatment is levodopa, which has better quality-of-life improvements in early Parkinson’s disease than other medications. Still, the success rate of medication is 14.9% only. Other than these patients are also treated with non-medications which are known as therapies like yoga, massage, music, and so on. As per the literature, most studies reveal that the therapies improved the quality of life by up to 58%. So, researchers need to be focused on the synthesis of novel drugs that create a high impact on the treatment of Parkinson’s disease. In this review paper, we discuss the pharmacological treatments for PD and discuss some of the current treatments. We hope this review article encourages the researchers to work in this field and develop new drugs against PD or permanent treatment for the person suffering from Parkinson.

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Abbreviations

AD:

Alzheimer’s disease

BBB:

blood-brain barrier

COMT:

catechol-O-methyltransferase

DA:

dopamine agonists

FDA:

food and drug administration

PD:

Parkinson disease

L-DOPA:

levodopa

LID:

levodopa induced dyskinesia’s

MAO-B:

monoamine oxidative inhibitor

NDRI:

norepinephrine and dopamine reuptake inhibitor

NMS:

non-motor symptoms

SN:

substantia nigra

SNRI:

serotonin and norepinephrine reuptake inhibitor

SSRI:

selective serotonin reuptake inhibitor

UPDRS:

Unified Parkinson Disease Rating Scale

UPR:

unfolded protein response.

References

  1. Sveinbjornsdottir S. The clinical symptoms of Parkinson’s disease. J Neurochem. 2016;139:318–24. https://doi.org/10.1111/jnc.13691

    Article  CAS  PubMed  Google Scholar 

  2. Cacabelos R. Parkinson’s disease: from pathogenesis to pharmacogenomics. Int J Mol Sci. 2017;18:551. https://doi.org/10.3390/ijms18030551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Koszła O, Stępnicki P, Zięba A, Grudzińska A, Matosiuk D, Kaczor AA. Current approaches and tools used in drug development against parkinson’s disease. Biomolecules. 2021;11:1–16. https://doi.org/10.3390/biom11060897

    Article  CAS  Google Scholar 

  4. Terashi H, Endo K, Kato H, Ido N, Aizawa H. Characteristics of sagittal spinopelvic alignment in patients with Parkinson’s disease. Acta Neurol Scand. 2022;145:53–62. https://doi.org/10.1111/ane.13521

    Article  PubMed  Google Scholar 

  5. Kimber TE. Approach to the patient with early Parkinson disease: diagnosis and management. Intern Med J. 2021;51:20–6. https://doi.org/10.1111/imj.15148

    Article  PubMed  Google Scholar 

  6. Sivanandy P, Leey TC, Xiang TC, Ling TC, Wey Han SA, Semilan SLA, et al. Systemic review on parkinson’s disease medications, emphasizing on three recently approved drugs to control parkinson’s symptoms. Int J Environ Res Public Health. 2022;19. https://doi.org/10.3390/ijerph19010364

  7. Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: a review. JAMA. 2020;323:548–60. https://doi.org/10.1001/jama.2019.22360

    Article  PubMed  Google Scholar 

  8. Tian Y, Chen R, Su Z. HMGB1 is a potential and challenging therapeutic target for Parkinson’s disease. Cell Mol Neurobiol. 2021;1:0123456789–58. https://doi.org/10.1007/s10571-021-01170-8

    Article  CAS  Google Scholar 

  9. Rozpędek-Kamińska W, Siwecka N, Wawrzynkiewicz A, Wojtczak R, Pytel D, Diehl JA, et al. The PERK-dependent molecular mechanisms as a novel therapeutic target for neurodegenerative diseases. Int J Mol Sci. 2020;21:1–40. https://doi.org/10.3390/ijms21062108

    Article  CAS  Google Scholar 

  10. Xu X, He X, Zhang Z, Chen Y, Li J, Ma S, et al. CREB inactivation by HDAC1/PP1c contributes to dopaminergic neurodegeneration in Parkinson’s disease. J Neurosci. 2022;42:4594–604. https://doi.org/10.1523/JNEUROSCI.1419-21.2022

    Article  CAS  PubMed  Google Scholar 

  11. Wittung-stafshede P. Gut power: modulation of human amyloid formation by amyloidogenic proteins in the gastrointestinal tract. Curr Opin Struct Biol. 2022;72:33–38. https://doi.org/10.1016/j.sbi.2021.07.009

    Article  CAS  PubMed  Google Scholar 

  12. Hansen CA, Miller DR, Annarumma S, Rusch CT, Ramirez-Zamora A, Khoshbouei H. Levodopa-induced dyskinesia: a historical review of Parkinson’s disease, dopamine, and modern advancements in research and treatment. J Neurol. 2022;269:2892–909. https://doi.org/10.1007/s00415-022-10963-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Group PS. A controlled trial of rasagiline in early Parkinson disease. Arch Neurol. 2012;59:1937–43

    Google Scholar 

  14. Gallazzi M, Mauri M, Bianchi ML, Riboldazzi G, Princiotta Cariddi L, Carimati F, et al. Selegiline reduces daytime sleepiness in patients with Parkinson’s disease. Brain Behav. 2021;11:1–5. https://doi.org/10.1002/brb3.1880

    Article  CAS  Google Scholar 

  15. Meira B, Degos B, Corsetti E, Doulazmi M, Berthelot E, Virbel-Fleischman C, et al. Long-term effect of apomorphine infusion in advanced Parkinson’s disease: a real-life study. npj Parkinson’s Dis. 2021;7:50–61. https://doi.org/10.1038/s41531-021-00194-7

    Article  CAS  Google Scholar 

  16. Cennamo M, Dragotto F, Favuzza E, Morelli A, Mencucci R. Amantadine therapy for Parkinson’s Disease: In Vivo Confocal Microscopy corneal findings, case report and revision of literature. BMC Ophthalmol. 2022;22:1–5. https://doi.org/10.1186/s12886-022-02410-1

    Article  Google Scholar 

  17. Li B, Yang Y, Wang Y, Zhang J, Ding J, Liu X, et al. Acetylation of NDUFV1 induced by a newly synthesized HDAC6 inhibitor HGC rescues dopaminergic neuron loss in Parkinson models. Science. 2021;24:102302 https://doi.org/10.1016/j.isci.2021.102302

    Article  CAS  Google Scholar 

  18. Layton JB, Forns J, Turner ME, Dempsey C, Bartsch JL, Anthony MS, et al. Falls and fractures in patients with Parkinson’s disease-related psychosis treated with Pimavanserin vs atypical antipsychotics: a cohort study. Drugs – Real World Outcomes. 2022;9:9–22. https://doi.org/10.1007/s40801-021-00284-1

    Article  PubMed  Google Scholar 

  19. Zhang X, Che C. Drug repurposing for Parkinson’s disease by integrating knowledge graph completion model and knowledge fusion of medical literature. Future Internet. 2021;13:1–13. https://doi.org/10.3390/fi13010014

    Article  Google Scholar 

  20. Reddy DH, Misra S, Medhi B. Advances in drug development for Parkinson’s disease: present status. Pharmacology. 2014;93:260–71. https://doi.org/10.1159/000362419

    Article  CAS  Google Scholar 

  21. James JH, Beck C. The silver book: Parkinson’s disease. Chronic disease and medical innovation in an aging nation. Alliance for Aging Research; 2019

  22. Ray Dorsey E, Elbaz A, Nichols E, Abd-Allah F, Abdelalim A, Adsuar JC, et al. Global, regional, and national burden of Parkinson’s disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17:939–53. https://doi.org/10.1016/S1474-4422(18)30295-3

    Article  Google Scholar 

  23. Soto-Lara M, Silva-Loredo M, Monroy-Córdoba JR, Flores-Ordoñez P, Cervera-Delgadillo NG, Carrillo-Mora P. Alternative medicine therapies in neurological disorders: prevalence, reasons and associated factors. A systematic review. Complement Ther Med. 2023;73:0–2. https://doi.org/10.1016/j.ctim.2023.102932

    Article  Google Scholar 

  24. Carter AM, Dioso ER, Romero B, Clinker CE, Lucke-Wold B. Complementary medicine and expressive arts therapy: adjuvant for recovery following neurosurgical procedures. OBM Integr Complement Med. 2023;08:1–14. https://doi.org/10.21926/obm.icm.2301007

    Article  CAS  Google Scholar 

  25. Jang JH, Kim J, Kwon O, Jung SY, Lee HJ, Cho SY, et al. Effectiveness and therapeutic mechanism of pharmacopuncture for pain in Parkinson’s disease: a study protocol for a pilot pragmatic randomized, assessor-blinded, usual care-controlled, three-arm parallel trial. Int J Environ Res Public Health. 2023;20. https://doi.org/10.3390/ijerph20031776

  26. Calderone A, Formenti M, Aprea F, Papa M, Alberghina L, Colangelo AM, et al. Comparing Alzheimer’s and Parkinson’s diseases networks using graph communities structure. BMC Syst Biol. 2016;10:1–10. https://doi.org/10.1186/s12918-016-0270-7

    Article  Google Scholar 

  27. Eliewi AG, Al-Garawi ZS, Al-Kazzaz FF, Atia AJK. Multi target-directed imidazole derivatives for neurodegenerative diseases. J Phys Conf Ser. 2021;1853:0–17. https://doi.org/10.1088/1742-6596/1853/1/012066

    Article  CAS  Google Scholar 

  28. Düzel E, Costagli M, Donatelli G, Speck O, Cosottini M. Studying Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis with 7-T magnetic resonance. Eur Radiol Exp. 2021;5:36 https://doi.org/10.1186/s41747-021-00221-5

    Article  PubMed  PubMed Central  Google Scholar 

  29. Mcgirr S, Venegas C, Swaminathan A. Alzheimer’s disease: a brief review. J Exp Neurol. 2020;1:89–98. https://doi.org/10.33696/Neurol.1.015

    Article  Google Scholar 

  30. Marie L. Parkinson’s dementia. The complete guide for people with Parkinson’s disease and their loved ones. 2020. 175–6. https://doi.org/10.2307/j.ctv15wxntx.61

  31. Biswas AK, Das S. Alzheimer and Parkinson’s disease—two faces of the same disease? J Alzheimer’s Dis Parkinson. 2016. 06. https://doi.org/10.4172/2161-0460.1000222

  32. Tamara P, Day GS, Smith DB, Rae-Grant A, Licking N, Armstrong MJ, et al. Dopaminergic therapy for motor symptoms in early Parkinson disease practice Guideline summary. Neurology. 2021;97:942–57. https://doi.org/10.1212/wnl.0000000000012868

    Article  Google Scholar 

  33. Kouli A, Torsney KM, Kuan W-L. Parkinson’s disease: etiology, neuropathology, and pathogenesis. Codon Publications. 2018:3–26. https://doi.org/10.15586/codonpublications.parkinsonsdisease.2018

  34. Xia R, Mao ZH. Progression of motor symptoms in Parkinson’s disease. Neurosci Bull. 2012;28:39–48. https://doi.org/10.1007/s12264-012-1050-z

    Article  PubMed  PubMed Central  Google Scholar 

  35. Höglund A, Hagell P, Broman JE, Pålhagen S, Sorjonen K, Fredrikson S, et al. Associations between fluctuations in daytime sleepiness and motor and non-motor symptoms in Parkinson’s disease. Mov Disord Clin Pract. 2021;8:44–50. https://doi.org/10.1002/mdc3.13102

    Article  PubMed  Google Scholar 

  36. Dong J, Cui Y, Li S, Le W. Current pharmaceutical treatments and alternative therapies of Parkinson’s disease. Curr Neuropharmacol. 2016;14:339–55. https://doi.org/10.2174/1570159x14666151120123025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Review N, Start WTO, Treatment S, Schapira AHV. Treatment options in the modern management of Parkinson disease. Arch Neurol. 2007;64:1083–8. https://doi.org/10.1001/archneur.64.8.1083

    Article  Google Scholar 

  38. Kumaresan M, Khan S. Spectrum of non-motor symptoms in Parkinson’s disease. Cureus. 2021;13. https://doi.org/10.7759/cureus.13275

  39. Sang Q, Liu X, Wang L, Qi L, Sun W, Wang W, et al. CircSNCA downregulation by pramipexole treatment mediates cell apoptosis and autophagy in Parkinson’s disease by targeting miR-7. Aging. 2018;10:1281–93. https://doi.org/10.18632/aging.101466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. AlDakheel A, Kalia LV, Lang AE. Pathogenesis-targeted, disease-modifying therapies in Parkinson disease. Neurotherapeutics. 2014;11:6–23. https://doi.org/10.1007/s13311-013-0218-1

    Article  CAS  PubMed  Google Scholar 

  41. Cuervo AM, Stafanis L, Fredenburg R, Lansbury PT, Sulzer D. Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy. Science. 2004;305:1292–5. https://doi.org/10.1126/science.1101738

    Article  CAS  PubMed  Google Scholar 

  42. Paillusson S, Gomez-Suaga P, Stoica R, Little D, Gissen P, Devine MJ, et al. α-Synuclein binds to the ER–mitochondria tethering protein VAPB to disrupt Ca2+ homeostasis and mitochondrial ATP production. Acta Neuropathol. 2017;134:129–49. https://doi.org/10.1007/s00401-017-1704-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Elkouzi A, Vedam-Mai V, Eisinger RS, Okun MS. Emerging therapies in Parkinson disease—repurposed drugs and new approaches. Nat Rev Neurol. 2019;15:204–23. https://doi.org/10.1038/s41582-019-0155-7

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ovallath S, Sulthana B. Levodopa: history and therapeutic applications. Ann Indian Acad Neurol. 2017;20:185–9. https://doi.org/10.4103/aian.AIAN_241_17

    Article  PubMed  PubMed Central  Google Scholar 

  45. Goldenberg MM. Medical management of Parkinson’s disease. Pharm Ther. 2008;33:590–6

    Google Scholar 

  46. Rao SK, Vakil SD, Calne DB, Hilson A, Rao SK, Lond D, et al. Augmenting the action of levodopa. Postgrad Med J. 1972;48:653–6. https://doi.org/10.1136/pgmj.48.565.653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ansari AJ, Khushtar M, Fatima N, Monawwar MT, Alhamd Khan MF. An overview on the diagnosis and approaches in pharmacological management of Parkinson’s disease. Res Rev J Neurosci. 2021;11:1–8. https://doi.org/10.37591/RRJoNS

    Article  Google Scholar 

  48. Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014;311:1670–83. https://doi.org/10.1001/jama.2014.3654

    Article  CAS  PubMed  Google Scholar 

  49. Wojciech DP, Dekundy A, Scheschonka A, Riederer P. Amantadine: reappraisal of the timeless diamond—target updates and novel therapeutic potentials. J Neural Transm. 2021;128:127–69. https://doi.org/10.1007/s00702-021-02306-2

    Article  CAS  Google Scholar 

  50. Hauser RA, Walsh RR, Pahwa R, Chernick D, Formella AE. Amantadine ER (Gocovri®) significantly increases on time without any dyskinesia: pooled analyses from pivotal trials in Parkinson’s disease. Front Neurol. 2021;12:1–9. https://doi.org/10.3389/fneur.2021.645706

    Article  Google Scholar 

  51. Crosby NJ, Deane K, Clarke CE. Amantadine for dyskinesia in Parkinson’s diseas. Cochrane Database Syst Rev. 2003;2010:003467 https://doi.org/10.1002/14651858.CD003467

    Article  Google Scholar 

  52. Hauser RA, Lytle J, Formella AE, Tanner CM. Amantadine delayed release/extended release capsules significantly reduce OFF time in Parkinson’s disease. npj Parkinson’s Dis. 2022;8:29–36. https://doi.org/10.1038/s41531-022-00291-1

    Article  CAS  Google Scholar 

  53. Rascols O, Tönges L, deVries T, Jaros M, Quartel A, Jacobs D, et al. Immediate-release/extended-release amantadine (OS320) to treat Parkinson’s disease with levodopa-induced dyskinesia: Analysis of the randomized, controlled ALLAY-LID studies. Parkinsonism Relat Disord. 2022;96:65–73. https://doi.org/10.1016/j.parkreldis.2022.01.022

    Article  CAS  Google Scholar 

  54. Borkar N, Mu H, Holm R. Challenges and trends in apomorphine drug delivery systems for the treatment of Parkinson’s disease. Asian J Pharm Sci. 2018;13:507–17. https://doi.org/10.1016/j.ajps.2017.11.004

    Article  PubMed  Google Scholar 

  55. Carbone F, Djamshidian A, Seppi K, Poewe W. Apomorphine for Parkinson’s disease: efficacy and safety of current and new formulation. CNS Drugs. 2019;33:905–18. https://doi.org/10.1007/s40263-019-00661-z

    Article  PubMed  PubMed Central  Google Scholar 

  56. Antonini A, Jenner P. Apomorphine infusion in advanced Parkinson disease. Nat Rev Neurol. 2018;14:693–4. https://doi.org/10.1038/s41582-018-0083-y

    Article  PubMed  Google Scholar 

  57. Christensen PB, Dupont E, Jensen NB. Apomorphine in the treatment of Parkinson disease. Ugeskr Laege. 1991;153:2631–4.

    CAS  Google Scholar 

  58. Cheer GM, Bang SM, Keating LM. Ropinirole: for the treatment of restless legs syndrome. CNS Drugs. 2004;18:747–54. https://doi.org/10.2165/00023210-200418110-00004

    Article  CAS  PubMed  Google Scholar 

  59. Silva S, Almeida AJ, Vale N. Importance of nanoparticles for the delivery of antiparkinsonian drugs. Pharmaceutics. 2021;13:508 https://doi.org/10.3390/pharmaceutics13040508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Shill HA, Stacy M. Update on ropinirole in the treatment of Parkinson’s disease. Neuropsychiatr Dis Treat. 2009;5:33–36. https://doi.org/10.2147/ndt.s3237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Nashatizadeh MM, Lyons KE, Pahwa R. A review of ropinirole prolonged release in Parkinson’s disease. Clin Interv Aging. 2009;4:179–86. https://doi.org/10.2147/cia.s3358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhang J, Gao X, Chen Y, Kong Q. Clinical observation of ropinirole hydrochloride in the treatment of Parkinson’s disease. Comput Math Methods Med. 2022;2022:1–7. https://doi.org/10.1155/2022/3989770

    Article  Google Scholar 

  63. Tábi T, Vécsei L, Youdim MB, Riederer P, Szökő É. Selegiline: a molecule with innovative potential. J Neural Transm. 2020;127:831–42. https://doi.org/10.1007/s00702-019-02082-0

    Article  PubMed  Google Scholar 

  64. Jost WH. A critical appraisal of MAO-B inhibitors in the treatment of Parkinson’s disease. J Neural Transm. 2022;129:723–36. https://doi.org/10.1007/s00702-022-02465-w

    Article  CAS  PubMed  Google Scholar 

  65. Bali N, Salve PS. Fabrication and evaluation of selegiline HCl embedded transdermal film for management of Parkinson’s disease. J Drug Deliv Ther. 2019;9:344–51. https://doi.org/10.22270/jddt.v9i2.2577

    Article  CAS  Google Scholar 

  66. Magyar K. The pharmacology of selegiline. Int Rev Neurobiol. 2011;100:65–84. https://doi.org/10.1016/B978-0-12-386467-3.00004-2

    Article  CAS  PubMed  Google Scholar 

  67. Robakis D, Fahn S. Defining the role of the monoamine oxidase-B inhibitors for Parkinson’s disease. CNS Drugs. 2015;29:433–41. https://doi.org/10.1007/s40263-015-0249-8

    Article  CAS  PubMed  Google Scholar 

  68. Lecht S, Haroutiunian S, Hoffman A, Lazarovici P. Rasagiline—a novel MAO B inhibitor in Parkinson’s disease therapy. Ther Clin Risk Manag. 2007;3:467–74

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Hudry J, Rinne JO, Keränen T, Eckert L, Cochran JM. Cost-utility model of Rasagiline in the treatment of advanced Parkinson’s disease in Finland. Ann Pharmacother. 2006;40:651–7. https://doi.org/10.1345/aph.1G454

    Article  CAS  PubMed  Google Scholar 

  70. Kano O, Ikeda K, Kiyozuka T, Iwamoto K, Ito H, Kawase Y, et al. Beneficial effect of pramipexole for motor function and depression in Parkinson’s disease. Neuropsychiatr Dis Treat. 2008;4:707–10. https://doi.org/10.2147/ndt.s2921

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wolfram E, Sommer B, Hartter S, Jost WH. Pramipexole extended release: a novel treatment option in Parkinson’s disease. Parkinson’s Dis. 2010;2010:612619 https://doi.org/10.4061/2010/612619

    Article  CAS  Google Scholar 

  72. Hauser RA, Giladi N, Poewe W, Brotchie J, Friedman H, Oren S, et al. P2B001 (extended release pramipexole and rasagiline): a new treatment option in development for Parkinson’s disease. Adv Ther. 2022;39:1881–94. https://doi.org/10.1007/s12325-022-02097-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. McAfee DA, Hadgraft J, Lane ME. Rotigotine: the first new chemical entity for transdermal drug delivery. Eur J Pharm Biopharm. 2014;88:586–93. https://doi.org/10.1016/j.ejpb.2014.08.007

    Article  CAS  PubMed  Google Scholar 

  74. Ouchi M, Kitta T, Chiba H, Higuchi M, Togo M, Abe-Takahashi Y, et al. Mechanisms of D1/D2-like dopaminergic agonist, rotigotine, on lower urinary tract function in rat model of Parkinson’s disease. Sci Rep. 2022;12:1–8. https://doi.org/10.1038/s41598-022-08612-3

    Article  CAS  Google Scholar 

  75. Raeder V, Boura I, Leta V, Jenner P, Reichmann H, Trenkwalder C, et al. Rotigotine transdermal patch for motor and non-motor parkinson’s disease: a review of 12 years’ clinical experience. CNS Drugs. 2021;35:215–31. https://doi.org/10.1007/s40263-020-00788-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Yeni Y, Wu X, Arman B. Anti-Parkinson drug from chemical medicines and herbal medicines: a review. Pharm Biomed Sci J 2022;3:45–58. https://doi.org/10.15408/pbsj.v3i1.20304

    Article  Google Scholar 

  77. Benitez A, Edens H, Fishman J, Moran K, Asgharnejad M. Rotigotine transdermal system: developing continuous dopaminergic delivery to treat Parkinson’s disease and restless legs syndrome. Ann NY Acad Sci. 2014;1329:45–66. https://doi.org/10.1111/nyas.12508

    Article  CAS  PubMed  Google Scholar 

  78. Schrag A. Entacapone in the treatment of Parkinson’s disease. Lancet Neurol. 2005;4:366–70. https://doi.org/10.1016/S1474-4422(05)70098-3

    Article  CAS  PubMed  Google Scholar 

  79. Jo M, Palma PN. Catechol-O-methyltransferase and Its Inhibitors in Parkinson’s disease. CNS Drug Rev. 2007;13:352–79. https://doi.org/10.1007/s40265-014-0343-0

    Article  CAS  Google Scholar 

  80. Salamon A, Zádori D, Szpisjak L, Klivényi P, Vécsei L. What is the impact of catechol-O-methyltransferase (COMT) on Parkinson’s disease treatment? Expert Opin Pharmacother. 2022;1:1123–8. https://doi.org/10.1080/14656566.2022.2060738

    Article  CAS  Google Scholar 

  81. Rizek SJ, Kumar P, Mandar N. An update on the diagnosis and treatment of Parkinson’s disease. CMAJ. 2016;188:1157–65. https://doi.org/10.1503/cmaj.151179

    Article  PubMed  PubMed Central  Google Scholar 

  82. Artusi CA, Sarro L, Imbalzano G, Fabbri M, Lopiano L. Safety and efficacy of tolcapone in Parkinson’s disease: systematic review. Eur J Clin Pharmacol. 2021;77:817–29. https://doi.org/10.1007/s00228-020-03081-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Saeedi Y, Ghadimi M, Rohani M, Emamikhah M, Shahidi G, Moghaddasi M, et al. Impact of anticholinergic drugs withdrawal on motor function in patients with Parkinson’s disease. Clin Neurol Neurosurg. 2021;202:106480 https://doi.org/10.1016/j.clineuro.2021.106480

    Article  PubMed  Google Scholar 

  84. Zhao J, Xu G, Feng C, Chen Y, Kang Y, Liu F, et al. Trihexyphenidyl induced malignant hyperthermia in a patient with Parkinson’s disease complicated with pneumonia: a case report. Medicines. 2020;99:2019–21. https://doi.org/10.1097/MD.0000000000020129

    Article  Google Scholar 

  85. Teixeira FG, Gago MF, Marques P, Moreira PS, Magalhães R, Sousa N, et al. Safinamide: a new hope for Parkinson’s disease? Drug Discov Today. 2018;23:736–44. https://doi.org/10.1016/j.drudis.2018.01.033

    Article  CAS  PubMed  Google Scholar 

  86. Wasan H, Singh D, KH R. Safinamide in neurological disorders and beyond: evidence from preclinical and clinical studies. Brain Res Bull. 2021;168:165–77. https://doi.org/10.1016/j.brainresbull.2020.12.018

    Article  CAS  PubMed  Google Scholar 

  87. Giossi R, Carrara F, Mazzari M, Lo Re F, Senatore M, Schicchi A, et al. Overall efficacy and safety of safinamide in Parkinson’s disease: a systematic review and a meta-analysis. Clin Drug Investig. 2021;41:321–39. https://doi.org/10.1007/s40261-021-01011-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Valldeoriola F, Grandas F, Arbelo JM, Blázquez Estrada M, Calopa Garriga M, Campos-Arillo VM, et al. Spanish expert consensus on the use of safinamide in Parkinson’s disease. Neurolía. 2021;36:666–72. https://doi.org/10.1016/j.nrleng.2018.04.004

    Article  CAS  Google Scholar 

  89. Sanger GJ, Andrews PLR. A history of drug discovery for treatment of nausea and vomiting and the implications for future research. Front Pharmacol. 2018;9:1–35. https://doi.org/10.3389/fphar.2018.00913

    Article  CAS  Google Scholar 

  90. Ye J, Hong P, Rex Schaefer R. Ondansetron: a selective 5-HT3 receptor antagonist and its applications in CNS-related disorders. CNS Drug Rev. 2001;7:199–13. https://doi.org/10.1111/j.1527-3458.2001.tb00195.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Tsitsipa E, Rogers J, Casalotti S, Belessiotis-Richards C, Zubko O, Weil RS, et al. Selective 5HT3 antagonists and sensory processing: a systematic review. Neuropsychopharmacology. 2022;47:880–90. https://doi.org/10.1038/s41386-021-01255-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Butler A, Hill JM, Ireland SJ, Jordan CC, Tyers MB. Pharmacological properties of GR38032F, a novel antagonist at 5‐HT3 receptors. Br J Pharmacol. 1988;94:397–12. https://doi.org/10.1111/j.1476-5381.1988.tb11542.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Stern ER, Shahab R, Grimaldi SJ, Leibu E, Murrough JW, Fleysher L, et al. High-dose ondansetron reduces activation of interoceptive and sensorimotor brain regions. Neuropsychopharmacology. 2019;44:390–8. https://doi.org/10.1038/s41386-018-0174-x

    Article  CAS  PubMed  Google Scholar 

  94. Leeser J, Lip H. Prevention of postoperative nausea and vomiting using ondansetron, a new, selective, 5-HT3 receptor antagonist. Anesth Analg. 1991;72:751–5. https://doi.org/10.1213/00000539-199106000-00005

    Article  CAS  PubMed  Google Scholar 

  95. Shin H-J, Koo B-W, Yoon J, Kim H, Do S-H, Na H-S. Melatonin reduces the endoplasmic reticulum stress and polyubiquitinated protein accumulation induced by repeated anesthesia exposure in Caenorhabditis elegans. Sci Rep. 2022;12:1–8. https://doi.org/10.1038/s41598-022-09853-y

    Article  CAS  Google Scholar 

  96. Mack JM, Schamne MG, Sampaio TB, Pértile RAN, Fernandes PACM, Markus RP, et al. Melatoninergic system in Parkinson’s disease: from neuroprotection to the management of motor and nonmotor symptoms. Oxid Med Cell Longev. 2016. https://doi.org/10.1155/2016/3472032

    Article  PubMed  PubMed Central  Google Scholar 

  97. Farnoosh G, Akbariqomi M, Badri T, Bagheri M, Izadi M. Efficacy of a low dose of melatonin as an adjunctive therapy in hospitalized patients with COVID-19: a randomized, double-blind clinical trial. Arch Med Res. 2022;53:79–85. https://doi.org/10.1016/j.arcmed.2021.06

    Article  CAS  PubMed  Google Scholar 

  98. Jiménez-Delgado A, Ortiz GG, Delgado-Lara DL, González-Usigli HA, González-Ortiz LJ, Cid-Hernández M, et al. Effect of melatonin administration on mitochondrial activity and oxidative stress markers in patients with Parkinson’s disease. Oxid Med Cell Longev. 2021. https://doi.org/10.1155/2021/5577541

  99. Sakellaropoulou A, Siamidi A. Melatonin/cyclodextrin inclusion complexes: a review. Molecules. 2022;27:445–60. https://doi.org/10.3390/molecules27020445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bruni O, Alonso-Alconada D, Besag F, Biran V, Braam W, Cortese S, et al. Current role of melatonin in pediatric neurology: clinical recommendations. Eur J Paediatr Neurol. 2015;19:122–33. https://doi.org/10.1016/j.ejpn.2014.12.007

    Article  PubMed  Google Scholar 

  101. Perez-Caballero L, Torres-Sanchez S, Bravo L, Mico JA, Berrocoso E. Fluoxetine: a case history of its discovery and preclinical development. Expert Opin Drug Discov. 2014;9:567–78. https://doi.org/10.1517/17460441.2014.907790

    Article  CAS  PubMed  Google Scholar 

  102. Mostert JP, Koch MW, Heerings M, Heersema DJ, De Keyser J. Therapeutic potential of fluoxetine in neurological disorders. CNS Neurosci Ther. 2008;14:153–64. https://doi.org/10.1111/j.1527-3458.2008.00040.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Hippius H. A historical perspective of clozapine. J Clin Psychiatry. 1999;60:22–3

    PubMed  Google Scholar 

  104. Gammon D, Cheng C, Volkovinskaia A, Baker GB, Dursun SM. Clozapine: why is it so uniquely effective in the treatment of a range of neuropsychiatric disorders? Biomolecules. 2021;11:1–19. https://doi.org/10.3390/biom11071030

    Article  CAS  Google Scholar 

  105. Fitzgerald RL, Herold DA. Improved CEDIA® benzodiazepine assay eliminates sertraline crossreactivity. J Anal Toxicol. 1997;21:32–35. https://doi.org/10.1093/jat/21.1.32

    Article  CAS  PubMed  Google Scholar 

  106. Dadić-Hero E, Ružić K, Grahovac T, Graovac M, Palijan TŽ, Šepić-Grahovac D. Allergic reactions—outcome of sertraline and escitalopram treatments. Psychiatr Danubina. 2011;23:120–2

    Google Scholar 

  107. Latorre MA, Pina Modrego PJ, Rodilla F, Catalán C, Calvo M. Parkinsonism and Parkinson’s disease associated with long-term administration of sertraline. J Clin Pharm Ther. 2001;26:111–2. https://doi.org/10.1046/j.1365-2710.2001.00307.x

    Article  Google Scholar 

  108. Huot P, Fox SH, Brotchie JM. Monoamine reuptake inhibitors in Parkinson’s disease. Parkinson’s Dis. 2015;2015:609428 https://doi.org/10.1155/2015/609428

    Article  Google Scholar 

  109. Kowalska M, Nowaczyk J, Fijałkowski Ł, Nowaczyk A. Paroxetine—overview of the molecular mechanisms of action. Int J Mol Sci. 2021;22:1–21. https://doi.org/10.3390/ijms22041662

    Article  CAS  Google Scholar 

  110. Gupta A, Sharma V, Singh L. Devastating depression of youth and its remedial drug: a review. Eur J Biomed Pharm Sci. 2018;5:962–71.

    Google Scholar 

  111. Vismara M, Benatti B, Nicolini G, Cova I, Monfrini E, Di Fonzo A, et al. Clinical uses of Bupropion in patients with Parkinson’s disease and comorbid depressive or neuropsychiatric symptoms: a scoping review. BMC Neurol. 2022;22:1–20. https://doi.org/10.1186/s12883-022-02668-4

    Article  Google Scholar 

  112. Raskin S, Durst R. Bupropion as the treatment of choice in depression associated with Parkinson’s disease and it’s various treatments. Med Hypotheses. 2010;75:544–6. https://doi.org/10.1016/j.mehy.2010.07.024

    Article  CAS  PubMed  Google Scholar 

  113. Stahl SM, Pradko JF, Haight BR, Modell JG, Rockett CB, Learned Coughlin S. A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. Prim Care Companion J Clin Psychiatry. 2004;06:159–66. https://doi.org/10.4088/pcc.v06n0403

    Article  Google Scholar 

  114. Peña E, Mata M, López-Manzanares L, Kurtis M, Eimil M, Martínez-Castrillo JC, et al. Antidepressants in Parkinson’s disease. Recommendations by the movement disorder study group of the Neurological Association of Madrid. Neurolía (Engl Ed). 2018;33:395–402. https://doi.org/10.1016/j.nrleng.2016.02.017

    Article  Google Scholar 

  115. Váradi C. Clinical features of Parkinson’s disease. Biology. 2020;9:103–16. https://doi.org/10.1002/9783527629480.ch2

    Article  PubMed  PubMed Central  Google Scholar 

  116. Werner P, Antonini A, Zijlmans JC, Burkhard PR, Vingerhoets F. Levodopa in the treatment of Parkinson’s disease: an old drug still going strong. Clin Interv Aging. 2010;5:229–38. https://doi.org/10.2147/cia.s6456

    Article  Google Scholar 

  117. Hou JGG, Lai EC. Non-motor symptoms of Parkinson’s disease. Int J Gerontol. 2007;1:53–64. https://doi.org/10.1016/S1873-9598(08)70024-3

    Article  Google Scholar 

  118. Habet S. The clinical pharmacology of entacapone (Comtan®) from the Food and Drug Administration (FDA) reviewer. Int J Neuropsychopharmacol. 2022;1–9. https://doi.org/10.1093/ijnp/pyac021

  119. Anttila EVJ, Leinonen SAK. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001;7:249–64. https://doi.org/10.1111/j.1527-3458.2001.tb00198.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are highly thankful to Chandigarh University, Gharuan for providing basic facility to write the review article.

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Authors and Affiliations

  1. Medicinal and Natural Product Laboratory, Department of Chemistry, Chandigarh University, Gharuan, Mohali, 140413, Punjab, India

    Nancy Saini, Neetu Singh, Navneet Kaur, Sonali Garg, Manvinder Kaur, Meenakshi Verma & Harvinder Singh Sohal

  2. Amity Institute of Pharmacy, Amity University Haryana, Manesar, 122413, India

    Asim Kumar

  3. Department of Chemistry, Punjabi University, Patiala, 147002, Punjab, India

    Kishanpal Singh

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Contributions

NS, MK, and HSS conceived the review. NS drafted the manuscript and shared the first authorship. NS, AM, MV, SG and KS collected the data. AM, KS, and MK analyzed the data and made tables. NS and HSS made the figures.

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Correspondence to Harvinder Singh Sohal.

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Saini, N., Singh, N., Kaur, N. et al. Motor and non-motor symptoms, drugs, and their mode of action in Parkinson’s disease (PD): a review. Med Chem Res 33, 580–599 (2024). https://doi.org/10.1007/s00044-024-03203-5

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