Generic placeholder image

Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Future Directions for Developing Non-dopaminergic Strategies for the Treatment of Parkinson’s Disease

Author(s): Daniel J. van Wamelen*, Valentina Leta, K. Ray Chaudhuri and Peter Jenner

Volume 22, Issue 10, 2024

Published on: 04 August, 2023

Page: [1606 - 1620] Pages: 15

DOI: 10.2174/1570159X21666230731110709

Price: $65

conference banner
Abstract

The symptomatic treatment of Parkinson’s disease (PD) has been dominated by the use of dopaminergic medication, but significant unmet need remains, much of which is related to non-motor symptoms and the involvement of non-dopaminergic transmitter systems. As such, little has changed in the past decades that has led to milestone advances in therapy and significantly improved treatment paradigms and patient outcomes, particularly in relation to symptoms unresponsive to levodopa. This review has looked at how pharmacological approaches to treatment are likely to develop in the near and distant future and will focus on two areas: 1) novel non-dopaminergic pharmacological strategies to control motor symptoms; and 2) novel non-dopaminergic approaches for the treatment of non-motor symptoms. The overall objective of this review is to use a ‘crystal ball’ approach to the future of drug discovery in PD and move away from the more traditional dopamine-based treatments. Here, we discuss promising non-dopaminergic and ‘dirty drugs’ that have the potential to become new key players in the field of Parkinson’s disease treatment.

Keywords: Parkinson’s disease, pharmacology, non-dopaminergic, drug targets, serotonin, acetylcholine, GABA.

Graphical Abstract
[1]
Parkinson, J. An essay on the shaking palsy. J. Neuropsychiatry Clin. Neurosci., 2002, 14(2), 223-236.
[http://dx.doi.org/10.1176/jnp.14.2.223] [PMID: 11983801]
[2]
Yahr, M.D.; Duvoisin, R.C.; Schear, M.J.; Barrett, R.E.; Hoehn, M.M. Treatment of parkinsonism with levodopa. Arch. Neurol., 1969, 21(4), 343-354.
[http://dx.doi.org/10.1001/archneur.1969.00480160015001] [PMID: 5820999]
[3]
Schwab, R.S.; England, A.C., Jr; Amantadine, H.C.L. Amantadine HCL (Symmetrel) and its relation to Levo-Dopa in the treatment of Parkinson’s disease. Trans. Am. Neurol. Assoc., 1969, 94, 85-90.
[PMID: 4907453]
[4]
Birchfield, R.I. Levodopa: Problems, promise, patience and persistence. Northwest Med., 1970, 69(8), 561-563.
[PMID: 5459300]
[5]
LeWitt, P.A.; Chaudhuri, K.R. Unmet needs in Parkinson disease: Motor and non-motor. Parkinsonism Relat. Disord., 2020, 80(Suppl. 1), S7-S12.
[http://dx.doi.org/10.1016/j.parkreldis.2020.09.024] [PMID: 33349582]
[6]
Politis, M.; Wu, K.; Molloy, S.; G Bain, P.; Chaudhuri, K.R.; Piccini, P. Parkinson’s disease symptoms: The patient’s perspective. Mov. Disord., 2010, 25(11), 1646-1651.
[http://dx.doi.org/10.1002/mds.23135] [PMID: 20629164]
[7]
Lane, E.L. L-DOPA for Parkinson’s disease-a bittersweet pill. Eur. J. Neurosci., 2019, 49(3), 384-398.
[http://dx.doi.org/10.1111/ejn.14119] [PMID: 30118169]
[8]
Chaudhuri, K.R.; Jenner, P.; Antonini, A. Dyskinesia Matters: But not as much as it used to. Mov. Disord., 2020, 35(5), 900-901.
[http://dx.doi.org/10.1002/mds.28047] [PMID: 32415717]
[9]
Leta, V.; Jenner, P.; Chaudhuri, K.R.; Antonini, A. Can therapeutic strategies prevent and manage dyskinesia in Parkinson’s disease? An update. Expert Opin. Drug Saf., 2019, 18(12), 1203-1218.
[http://dx.doi.org/10.1080/14740338.2019.1681966] [PMID: 31619083]
[10]
Goetz, C.G. The history of Parkinson’s disease: Early clinical descriptions and neurological therapies. Cold Spring Harb. Perspect. Med., 2011, 1(1), a008862.
[http://dx.doi.org/10.1101/cshperspect.a008862] [PMID: 22229124]
[11]
van Wamelen, D.J.; Sauerbier, A.; Leta, V.; Rodriguez-Blazquez, C.; Falup-Pecurariu, C.; Rodriguez-Violante, M.; Rizos, A.; Tsuboi, Y.; Metta, V.; Bhidayasiri, R.; Bhattacharya, K.; Borgohain, R.; Prashanth, L.K.; Rosales, R.; Lewis, S.; Fung, V.; Behari, M.; Goyal, V.; Kishore, A.; Lloret, S.P.; Martinez-Martin, P.; Chaudhuri, K.R. Cross-sectional analysis of the Parkinson’s disease non-motor international longitudinal Study baseline non-motor characteristics, geographical distribution and impact on quality of life. Sci. Rep., 2021, 11(1), 9611.
[http://dx.doi.org/10.1038/s41598-021-88651-4] [PMID: 33953218]
[12]
Martinez-Martin, P.; Schrag, A.; Weintraub, D.; Rizos, A.; Rodriguez-Blazquez, C.; Chaudhuri, K.R. Pilot study of the international parkinson and movement disorder society-sponsored Non-motor Rating Scale (MDS-NMS). Mov. Disord. Clin. Pract., 2019, 6(3), 227-234.
[http://dx.doi.org/10.1002/mdc3.12728] [PMID: 30949554]
[13]
Rosqvist, K.; Odin, P.; Hagell, P.; Iwarsson, S.; Nilsson, M.H.; Storch, A. Dopaminergic effect on non-motor symptoms in late stage Parkinson’s Disease. J. Parkinsons Dis., 2018, 8(3), 409-420.
[http://dx.doi.org/10.3233/JPD-181380] [PMID: 30056433]
[14]
Wamelen, D.J.V.; Rukavina, K.; Podlewska, A.M.; Chaudhuri, K.R. Advances in the pharmacological and non-pharmacological management of non-motor symptoms in Parkinson’s disease: An update since 2017. Curr. Neuropharmacol., 2023, 21(8), 1786-1805.
[http://dx.doi.org/10.2174/1570159X20666220315163856] [PMID: 35293295]
[15]
Rota, S.; Urso, D.; van Wamelen, D.J.; Leta, V.; Boura, I.; Odin, P.; Espay, A.J.; Jenner, P.; Chaudhuri, K.R. Why do ‘OFF’ periods still occur during continuous drug delivery in Parkinson’s disease? Transl. Neurodegener., 2022, 11(1), 43.
[http://dx.doi.org/10.1186/s40035-022-00317-x] [PMID: 36229860]
[16]
Brotchie, J.M. Nondopaminergic mechanisms in levodopa-induced dyskinesia. Mov. Disord., 2005, 20(8), 919-931.
[http://dx.doi.org/10.1002/mds.20612] [PMID: 16007614]
[17]
Jenner, P. Pathophysiology and biochemistry of dyskinesia: Clues for the development of non-dopaminergic treatments. J. Neurol., 2000, 247(S2), II43-II50.
[http://dx.doi.org/10.1007/PL00007760] [PMID: 10991665]
[18]
Stayte, S.; Vissel, B. Advances in non-dopaminergic treatments for Parkinson’s disease. Front. Neurosci., 2014, 8, 113.
[http://dx.doi.org/10.3389/fnins.2014.00113] [PMID: 24904259]
[19]
Schapira, A.H.V.; Chaudhuri, K.R.; Jenner, P. Erratum: Non-motor features of Parkinson disease. Nat. Rev. Neurosci., 2017, 18(8), 509.
[http://dx.doi.org/10.1038/nrn.2017.91] [PMID: 28720825]
[20]
Seppi, K.; Ray Chaudhuri, K.; Coelho, M.; Fox, S.H.; Katzenschlager, R.; Perez Lloret, S.; Weintraub, D.; Sampaio, C.; Chahine, L.; Hametner, E-M.; Heim, B.; Lim, S-Y.; Poewe, W.; Djamshidian-Tehrani, A. Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Mov. Disord., 2019, 34(2), 180-198.
[http://dx.doi.org/10.1002/mds.27602] [PMID: 30653247]
[21]
Dafsari, H.S.; Martinez-Martin, P.; Rizos, A.; Trost, M.; Santos Ghilardi, M.G.; Reddy, P.; Sauerbier, A.; Petry-Schmelzer, J.N.; Kramberger, M.; Borgemeester, R.W.K.; Barbe, M.T.; Ashkan, K.; Silverdale, M.; Evans, J.; Odin, P.; Fonoff, E.T.; Fink, G.R.; Henriksen, T.; Ebersbach, G.; Pirtošek, Z.; Visser-Vandewalle, V.; Antonini, A.; Timmermann, L.; Ray Chaudhuri, K. EuroInf 2: Subthalamic stimulation, apomorphine, and levodopa infusion in Parkinson’s disease. Mov. Disord., 2019, 34(3), 353-365.
[http://dx.doi.org/10.1002/mds.27626] [PMID: 30719763]
[22]
Martinez-Martin, P.; Reddy, P.; Katzenschlager, R.; Antonini, A.; Todorova, A.; Odin, P.; Henriksen, T.; Martin, A.; Calandrella, D.; Rizos, A.; Bryndum, N.; Glad, A.; Dafsari, H.S.; Timmermann, L.; Ebersbach, G.; Kramberger, M.G.; Samuel, M.; Wenzel, K.; Tomantschger, V.; Storch, A.; Reichmann, H.; Pirtosek, Z.; Trost, M.; Svenningsson, P.; Palhagen, S.; Volkmann, J.; Chaudhuri, K.R. EuroInf: A multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson’s disease. Mov. Disord., 2015, 30(4), 510-516.
[http://dx.doi.org/10.1002/mds.26067] [PMID: 25382161]
[23]
Leta, V.; Dafsari, H.S.; Sauerbier, A.; Metta, V.; Titova, N.; Timmermann, L.; Ashkan, K.; Samuel, M.; Pekkonen, E.; Odin, P.; Antonini, A.; Martinez-Martin, P.; Parry, M.; van Wamelen, D.J.; Ray Chaudhuri, K. Personalised advanced therapies in parkinson’s disease: The role of non-motor symptoms profile. J. Pers. Med., 2021, 11(8), 773.
[http://dx.doi.org/10.3390/jpm11080773] [PMID: 34442417]
[24]
Mantovani, E.; Zucchella, C.; Argyriou, A.A.; Tamburin, S. Treatment for cognitive and neuropsychiatric non-motor symptoms in Parkinson’s disease: current evidence and future perspectives. Expert Rev. Neurother., 2023, 23(1), 25-43.
[http://dx.doi.org/10.1080/14737175.2023.2173576] [PMID: 36701529]
[25]
Titova, N.; Chaudhuri, K.R. Non-motor Parkinson disease: New concepts and personalised management. Med. J. Aust., 2018, 208(9), 404-409.
[http://dx.doi.org/10.5694/mja17.00993] [PMID: 29764353]
[26]
Sauerbier, A.; Violante, M.R.; Arriaga, A.C.; Rizos, A.; Trivedi, D.; Martinez-Martin, P.; Parry, M.; Rosa-Grilo, M.; Brown, R.; Chaudhuri, K. Parkinson’s disease phenotype across different ethnic groups: comparison of non-motor symptoms in patients living in the United Kingdom and Mexico. Mov. Disord., 2017, 32.
[27]
Jenner, P. The treatment of levodopa-induced dyskinesias: Surfing the serotoninergic wave. Mov. Disord., 2018, 33(11), 1670-1672.
[http://dx.doi.org/10.1002/mds.27525] [PMID: 30485909]
[28]
Sun, C.; Armstrong, M.J. Treatment of Parkinson’s Disease with cognitive impairment: Current approaches and future directions. Behav. Sci., 2021, 11(4), 54.
[http://dx.doi.org/10.3390/bs11040054] [PMID: 33920698]
[29]
Cenci, M.A.; Skovgård, K.; Odin, P. Non-dopaminergic approaches to the treatment of motor complications in Parkinson’s disease. Neuropharmacology, 2022, 210, 109027.
[http://dx.doi.org/10.1016/j.neuropharm.2022.109027] [PMID: 35292330]
[30]
Takashima, H.; Terada, T.; Bunai, T.; Matsudaira, T.; Obi, T.; Ouchi, Y. In vivo illustration of altered dopaminergic and GABAergic systems in early Parkinson’s Disease. Front. Neurol., 2022, 13, 880407.
[http://dx.doi.org/10.3389/fneur.2022.880407] [PMID: 35655619]
[31]
Qamar, M.A.; Sauerbier, A.; Politis, M.; Carr, H.; Loehrer, P.A.; Chaudhuri, K.R. Presynaptic dopaminergic terminal imaging and non-motor symptoms assessment of Parkinson’s disease: Evidence for dopaminergic basis? NPJ Parkinsons Dis., 2017, 3(1), 5.
[http://dx.doi.org/10.1038/s41531-016-0006-9] [PMID: 28649605]
[32]
Altwal, F.; Moon, C.; West, A.R.; Steiner, H. The multimodal serotonergic agent vilazodone inhibits L-DOPA-induced gene regulation in striatal projection neurons and associated dyskinesia in an animal model of Parkinson’s disease. Cells, 2020, 9(10), 2265.
[http://dx.doi.org/10.3390/cells9102265] [PMID: 33050305]
[33]
Mestre, T.A.; Fereshtehnejad, S.M.; Berg, D.; Bohnen, N.I.; Dujardin, K.; Erro, R.; Espay, A.J.; Halliday, G.; van Hilten, J.J.; Hu, M.T.; Jeon, B.; Klein, C.; Leentjens, A.F.G.; Marinus, J.; Mollenhauer, B.; Postuma, R.; Rajalingam, R.; Rodríguez-Violante, M.; Simuni, T.; Surmeier, D.J.; Weintraub, D.; McDermott, M.P.; Lawton, M.; Marras, C. Parkinson’s Disease subtypes: Critical appraisal and recommendations. J. Parkinsons Dis., 2021, 11(2), 395-404.
[http://dx.doi.org/10.3233/JPD-202472] [PMID: 33682731]
[34]
Mu, J.; Chaudhuri, K.R.; Bielza, C.; de Pedro-Cuesta, J.; Larrañaga, P.; Martinez-Martin, P. Parkinson’s Disease subtypes identified from cluster analysis of motor and non-motor symptoms. Front. Aging Neurosci., 2017, 9, 301.
[http://dx.doi.org/10.3389/fnagi.2017.00301] [PMID: 28979203]
[35]
Fereshtehnejad, S.M.; Zeighami, Y.; Dagher, A.; Postuma, R.B. Clinical criteria for subtyping Parkinson’s disease: Biomarkers and longitudinal progression. Brain, 2017, 140(7), 1959-1976.
[http://dx.doi.org/10.1093/brain/awx118] [PMID: 28549077]
[36]
Sauerbier, A.; Jenner, P.; Todorova, A.; Chaudhuri, K.R. Non motor subtypes and Parkinson’s disease. Parkinsonism Relat. Disord., 2016, 22(Suppl. 1), S41-S46.
[http://dx.doi.org/10.1016/j.parkreldis.2015.09.027] [PMID: 26459660]
[37]
Classen, J.; Koschel, J.; Oehlwein, C.; Seppi, K.; Urban, P.; Winkler, C.; Wüllner, U.; Storch, A. Nonmotor fluctuations: Phenotypes, pathophysiology, management, and open issues. J. Neural Transm., 2017, 124(8), 1029-1036.
[http://dx.doi.org/10.1007/s00702-017-1757-0] [PMID: 28702850]
[38]
Nemade, D.; Subramanian, T.; Shivkumar, V. An update on medical and surgical treatments of Parkinson’s Disease. Aging Dis., 2021, 12(4), 1021-1035.
[http://dx.doi.org/10.14336/AD.2020.1225] [PMID: 34221546]
[39]
Latif, S.; Jahangeer, M.; Maknoon Razia, D.; Ashiq, M.; Ghaffar, A.; Akram, M.; El Allam, A.; Bouyahya, A.; Garipova, L.; Ali Shariati, M.; Thiruvengadam, M.; Azam Ansari, M. Dopamine in Parkinson’s disease. Clin. Chim. Acta, 2021, 522, 114-126.
[http://dx.doi.org/10.1016/j.cca.2021.08.009] [PMID: 34389279]
[40]
Svensson, K.A.; Hao, J.; Bruns, R.F. Positive allosteric modulators of the dopamine D1 receptor: A new mechanism for the treatment of neuropsychiatric disorders. Adv. Pharmacol., 2019, 86, 273-305.
[http://dx.doi.org/10.1016/bs.apha.2019.06.001] [PMID: 31378255]
[41]
Marino, R.A.; Levy, R. Differential effects of D1 and D2 dopamine agonists on memory, motivation, learning and response time in non-human primates. Eur. J. Neurosci., 2019, 49(2), 199-214.
[http://dx.doi.org/10.1111/ejn.14208] [PMID: 30326151]
[42]
Lanza, K.; Meadows, S.M.; Chambers, N.E.; Nuss, E.; Deak, M.M.; Ferré, S.; Bishop, C. Behavioral and cellular dopamine D1 and D3 receptor-mediated synergy: Implications for L-DOPA-induced dyskinesia. Neuropharmacology, 2018, 138, 304-314.
[http://dx.doi.org/10.1016/j.neuropharm.2018.06.024] [PMID: 29936243]
[43]
Sugiyama, K.; Kuroiwa, M.; Shuto, T.; Ohnishi, Y.N.; Kawahara, Y.; Miyamoto, Y.; Fukuda, T.; Nishi, A. Subregion-specific regulation of dopamine D1 receptor signaling in the striatum: Implication for L-DOPA-induced dyskinesia. J. Neurosci., 2021, 41(30), 6388-6414.
[http://dx.doi.org/10.1523/JNEUROSCI.0373-21.2021] [PMID: 34131032]
[44]
Cerri, S.; Blandini, F. An update on the use of non-ergot dopamine agonists for the treatment of Parkinson’s disease. Expert Opin. Pharmacother., 2020, 21(18), 2279-2291.
[http://dx.doi.org/10.1080/14656566.2020.1805432] [PMID: 32804544]
[45]
Garcia-Ruiz, P.J. Impulse control disorders and dopamine-related creativity: Pathogenesis and mechanism, short review, and hypothesis. Front. Neurol., 2018, 9, 1041.
[http://dx.doi.org/10.3389/fneur.2018.01041] [PMID: 30574117]
[46]
Barbosa, P.; Hapuarachchi, B.; Djamshidian, A.; Strand, K.; Lees, A.J.; de Silva, R.; Holton, J.L.; Warner, T.T. Lower nucleus accumbens α-synuclein load and D3 receptor levels in Parkinson’s disease with impulsive compulsive behaviours. Brain, 2019, 142(11), 3580-3591.
[http://dx.doi.org/10.1093/brain/awz298] [PMID: 31603207]
[47]
Paudel, P.; Seong, S.H.; Jung, H.A.; Choi, J.S. Characterizing fucoxanthin as a selective dopamine D3/D4 receptor agonist: Relevance to Parkinson’s disease. Chem. Biol. Interact., 2019, 310, 108757.
[http://dx.doi.org/10.1016/j.cbi.2019.108757] [PMID: 31323226]
[48]
Paudel, P.; Seong, S.H.; Wu, S.; Park, S.; Jung, H.A.; Choi, J.S. Eckol as a potential therapeutic against neurodegenerative diseases targeting dopamine D3/D4 receptors. Mar. Drugs, 2019, 17(2), 108.
[http://dx.doi.org/10.3390/md17020108] [PMID: 30744179]
[49]
Hui, Y.; Du, C.; Xu, T.; Zhang, Q.; Tan, H.; Liu, J. Dopamine D4 receptors in the lateral habenula regulate depression-related behaviors via a pre-synaptic mechanism in experimental Parkinson’s disease. Neurochem. Int., 2020, 140, 104844.
[http://dx.doi.org/10.1016/j.neuint.2020.104844] [PMID: 32891683]
[50]
Allen, N.E.; Canning, C.G.; Almeida, L.R.S.; Bloem, B.R.; Keus, S.H.; Löfgren, N.; Nieuwboer, A.; Verheyden, G.S.; Yamato, T.P.; Sherrington, C. Interventions for preventing falls in Parkinson’s disease. Cochrane Database Syst. Rev., 2022, 6(6), CD011574.
[PMID: 35665915]
[51]
Titova, N.; Qamar, M.A.; Chaudhuri, K.R. The nonmotor features of Parkinson’s Disease. Int. Rev. Neurobiol., 2017, 132, 33-54.
[http://dx.doi.org/10.1016/bs.irn.2017.02.016] [PMID: 28554413]
[52]
Lange, K.W.; Wells, F.R.; Jenner, P.; Marsden, C.D. Altered muscarinic and nicotinic receptor densities in cortical and subcortical brain regions in Parkinson’s disease. J. Neurochem., 1993, 60(1), 197-203.
[http://dx.doi.org/10.1111/j.1471-4159.1993.tb05838.x] [PMID: 8417140]
[53]
Bohnen, N.I.; Albin, R.L. The cholinergic system and Parkinson disease. Behav. Brain Res., 2011, 221(2), 564-573.
[http://dx.doi.org/10.1016/j.bbr.2009.12.048] [PMID: 20060022]
[54]
Calabresi, P.; Picconi, B.; Parnetti, L.; Di Filippo, M. A convergent model for cognitive dysfunctions in Parkinson’s disease: The critical dopamine–acetylcholine synaptic balance. Lancet Neurol., 2006, 5(11), 974-983.
[http://dx.doi.org/10.1016/S1474-4422(06)70600-7] [PMID: 17052664]
[55]
Quik, M.; O’Leary, K.; Tanner, C.M. Nicotine and Parkinson’s disease: Implications for therapy. Mov. Disord., 2008, 23(12), 1641-1652.
[http://dx.doi.org/10.1002/mds.21900] [PMID: 18683238]
[56]
Moran, S.P.; Maksymetz, J.; Conn, P.J. Targeting muscarinic acetylcholine receptors for the treatment of psychiatric and neurological disorders. Trends Pharmacol. Sci., 2019, 40(12), 1006-1020.
[http://dx.doi.org/10.1016/j.tips.2019.10.007] [PMID: 31711626]
[57]
Melani, R.; Tritsch, N.X. Inhibitory co-transmission from midbrain dopamine neurons relies on presynaptic GABA uptake. Cell Rep., 2022, 39(3), 110716.
[http://dx.doi.org/10.1016/j.celrep.2022.110716] [PMID: 35443174]
[58]
Shetty, A.K.; Bates, A. Potential of GABA-ergic cell therapy for schizophrenia, neuropathic pain, and Alzheimer's and Parkinson's diseases. Brain Res., 2016, 1638(Pt A), 74-87.
[http://dx.doi.org/10.1016/j.brainres.2015.09.019] [PMID: 26423935]
[59]
Ziegler, M.; Fournier, V.; Bathien, N.; Morselli, P.L.; Rondot, P. Therapeutic response to progabide in neuroleptic- and L-dopa-induced dyskinesias. Clin. Neuropharmacol., 1987, 10(3), 238-246.
[http://dx.doi.org/10.1097/00002826-198706000-00005] [PMID: 2900682]
[60]
Tyagi, R.K.; Bisht, R.; Pant, J.; kumar, P.; Majeed, A.B.A.; Prakash, A. Possible role of GABA-B receptor modulation in MPTP induced Parkinson’s disease in rats. Exp. Toxicol. Pathol., 2015, 67(2), 211-217.
[http://dx.doi.org/10.1016/j.etp.2014.12.001] [PMID: 25547370]
[61]
Sgambato-Faure, V.; Cenci, M.A. Glutamatergic mechanisms in the dyskinesias induced by pharmacological dopamine replacement and deep brain stimulation for the treatment of Parkinson’s disease. Prog. Neurobiol., 2012, 96(1), 69-86.
[http://dx.doi.org/10.1016/j.pneurobio.2011.10.005] [PMID: 22075179]
[62]
O’Gorman Tuura, R.L.; Baumann, C.R.; Baumann-Vogel, H. Beyond dopamine: GABA, glutamate, and the axial symptoms of Parkinson disease. Front. Neurol., 2018, 9, 806.
[http://dx.doi.org/10.3389/fneur.2018.00806] [PMID: 30319535]
[63]
Duty, S. Targeting glutamate receptors to tackle the pathogenesis, clinical symptoms and levodopa-induced dyskinesia associated with Parkinson’s disease. CNS Drugs, 2012, 26(12), 1017-1032.
[http://dx.doi.org/10.1007/s40263-012-0016-z] [PMID: 23114872]
[64]
Ahmed, I.; Bose, S.K.; Pavese, N.; Ramlackhansingh, A.; Turkheimer, F.; Hotton, G.; Hammers, A.; Brooks, D.J. Glutamate NMDA receptor dysregulation in Parkinson’s disease with dyskinesias. Brain, 2011, 134(4), 979-986.
[http://dx.doi.org/10.1093/brain/awr028] [PMID: 21371994]
[65]
Dimatteo, V.; Pierucci, M.; Esposito, E.; Crescimanno, G.; Benigno, A.; Digiovanni, G. Serotonin modulation of the basal ganglia circuitry: Therapeutic implication for Parkinson’s disease and other motor disorders. Prog. Brain Res., 2008, 172, 423-463.
[http://dx.doi.org/10.1016/S0079-6123(08)00921-7] [PMID: 18772045]
[66]
Daubert, E.A.; Condron, B.G. Serotonin: A regulator of neuronal morphology and circuitry. Trends Neurosci., 2010, 33(9), 424-434.
[http://dx.doi.org/10.1016/j.tins.2010.05.005] [PMID: 20561690]
[67]
Carta, M.; Tronci, E. Serotonin system implication in L-DOPA-induced dyskinesia: From animal models to clinical investigations. Front. Neurol., 2014, 5, 78.
[http://dx.doi.org/10.3389/fneur.2014.00078] [PMID: 24904522]
[68]
Carta, M.; Carlsson, T.; Muñoz, A.; Kirik, D.; Björklund, A. Involvement of the serotonin system in l-dopa-induced dyskinesias. Parkinsonism Relat. Disord., 2008, 14(Suppl. 2), S154-S158.
[http://dx.doi.org/10.1016/j.parkreldis.2008.04.021] [PMID: 18579429]
[69]
Politis, M.; Niccolini, F. Serotonin in Parkinson’s disease. Behav. Brain Res., 2015, 277, 136-145.
[http://dx.doi.org/10.1016/j.bbr.2014.07.037] [PMID: 25086269]
[70]
Politis, M.; Wu, K.; Loane, C.; Brooks, D.J.; Kiferle, L.; Turkheimer, F.E.; Bain, P.; Molloy, S.; Piccini, P. Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients. J. Clin. Invest., 2014, 124(3), 1340-1349.
[http://dx.doi.org/10.1172/JCI71640] [PMID: 24531549]
[71]
Conti, M.M.; Ostock, C.Y.; Lindenbach, D.; Goldenberg, A.A.; Kampton, E.; Dell’isola, R.; Katzman, A.C.; Bishop, C. Effects of prolonged selective serotonin reuptake inhibition on the development and expression of l-DOPA-induced dyskinesia in hemi-parkinsonian rats. Neuropharmacology, 2014, 77, 1-8.
[http://dx.doi.org/10.1016/j.neuropharm.2013.09.017] [PMID: 24067924]
[72]
Bezard, E.; Carta, M. Could the serotonin theory give rise to a treatment for levodopa-induced dyskinesia in Parkinson’s disease? Brain, 2015, 138(4), 829-830.
[http://dx.doi.org/10.1093/brain/awu407] [PMID: 25669729]
[73]
Isaacson, S.H.; Ballard, C.G.; Kreitzman, D.L.; Coate, B.; Norton, J.C.; Fernandez, H.H.; Ilic, T.V.; Azulay, J.P.; Ferreira, J.J.; Abler, V.; Stankovic, S. Efficacy results of pimavanserin from a multi-center, open-label extension study in Parkinson’s disease psychosis patients. Parkinsonism Relat. Disord., 2021, 87, 25-31.
[http://dx.doi.org/10.1016/j.parkreldis.2021.04.012] [PMID: 33933853]
[74]
Isaacson, S.H.; Coate, B.; Norton, J.; Stankovic, S. Blinded SAPS-PD assessment after 10 weeks of pimavanserin treatment for Parkinson’s disease psychosis. J. Parkinsons Dis., 2020, 10(4), 1389-1396.
[http://dx.doi.org/10.3233/JPD-202047] [PMID: 32716320]
[75]
DeKarske, D.; Alva, G.; Aldred, J.L.; Coate, B.; Cantillon, M.; Jacobi, L.; Nunez, R.; Norton, J.C.; Abler, V. An Open-Label, 8-week study of safety and efficacy of pimavanserin treatment in adults with Parkinson’s Disease and depression. J. Parkinsons Dis., 2020, 10(4), 1751-1761.
[http://dx.doi.org/10.3233/JPD-202058] [PMID: 32804101]
[76]
Espay, A.J.; Guskey, M.T.; Norton, J.C.; Coate, B.; Vizcarra, J.A.; Ballard, C.; Factor, S.A.; Friedman, J.H.; Lang, A.E.; Larsen, N.J.; Andersson, C.; Fredericks, D.; Weintraub, D. Pimavanserin for Parkinson’s Disease psychosis: Effects stratified by baseline cognition and use of cognitive-enhancing medications. Mov. Disord., 2018, 33(11), 1769-1776.
[http://dx.doi.org/10.1002/mds.27488] [PMID: 30387904]
[77]
Haskó, G.; Pacher, P.; Sylvester Vizi, E.; Illes, P. Adenosine receptor signaling in the brain immune system. Trends Pharmacol. Sci., 2005, 26(10), 511-516.
[http://dx.doi.org/10.1016/j.tips.2005.08.004] [PMID: 16125796]
[78]
Jenner, P.; Mori, A.; Kanda, T. Can adenosine A2A receptor antagonists be used to treat cognitive impairment, depression or excessive sleepiness in Parkinson’s disease? Parkinsonism Relat. Disord., 2020, 80(Suppl. 1), S28-S36.
[http://dx.doi.org/10.1016/j.parkreldis.2020.09.022] [PMID: 33349577]
[79]
Kanda, T.; Jenner, P. Can adenosine A2A receptor antagonists modify motor behavior and dyskinesia in experimental models of Parkinson’s disease? Parkinsonism Relat. Disord., 2020, 80(Suppl. 1), S21-S27.
[http://dx.doi.org/10.1016/j.parkreldis.2020.09.026] [PMID: 33349576]
[80]
Pinna, A. Adenosine A2A receptor antagonists in Parkinson’s disease: Progress in clinical trials from the newly approved istradefylline to drugs in early development and those already discontinued. CNS Drugs, 2014, 28(5), 455-474.
[http://dx.doi.org/10.1007/s40263-014-0161-7] [PMID: 24687255]
[81]
Hodgson, R.A.; Bertorelli, R.; Varty, G.B.; Lachowicz, J.E.; Forlani, A.; Fredduzzi, S.; Cohen-Williams, M.E.; Higgins, G.A.; Impagnatiello, F.; Nicolussi, E.; Parra, L.E.; Foster, C.; Zhai, Y.; Neustadt, B.R.; Stamford, A.W.; Parker, E.M.; Reggiani, A.; Hunter, J.C. Characterization of the potent and highly selective A2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4, 3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] in rodent models of movement disorders and depression. J. Pharmacol. Exp. Ther., 2009, 330(1), 294-303.
[http://dx.doi.org/10.1124/jpet.108.149617] [PMID: 19332567]
[82]
Hattori, N.; Kikuchi, M.; Adachi, N.; Hewitt, D.; Huyck, S.; Saito, T. Adjunctive preladenant: A placebo-controlled, dose-finding study in Japanese patients with Parkinson’s disease. Parkinsonism Relat. Disord., 2016, 32, 73-79.
[http://dx.doi.org/10.1016/j.parkreldis.2016.08.020] [PMID: 27632893]
[83]
Stocchi, F.; Rascol, O.; Hauser, R.A.; Huyck, S.; Tzontcheva, A.; Capece, R.; Ho, T.W.; Sklar, P.; Lines, C.; Michelson, D.; Hewitt, D.J. Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease. Neurology, 2017, 88(23), 2198-2206.
[http://dx.doi.org/10.1212/WNL.0000000000004003] [PMID: 28490648]
[84]
Hauser, R.A.; Stocchi, F.; Rascol, O.; Huyck, S.B.; Capece, R.; Ho, T.W.; Sklar, P.; Lines, C.; Michelson, D.; Hewitt, D. Preladenant as an adjunctive therapy with levodopa in Parkinson disease: Two randomized clinical trials and lessons learned. JAMA Neurol., 2015, 72(12), 1491-1500.
[http://dx.doi.org/10.1001/jamaneurol.2015.2268] [PMID: 26523919]
[85]
LeWitt, P.A.; Aradi, S.D.; Hauser, R.A.; Rascol, O. The challenge of developing adenosine A2A antagonists for Parkinson disease: Istradefylline, preladenant, and tozadenant. Parkinsonism Relat. Disord., 2020, 80(Suppl. 1), S54-S63.
[http://dx.doi.org/10.1016/j.parkreldis.2020.10.027] [PMID: 33349581]
[86]
Fabbri, M.; Perez-Lloret, S.; Rascol, O. Therapeutic strategies for Parkinson’s disease: Promising agents in early clinical development. Expert Opin. Investig. Drugs, 2020, 29(11), 1249-1267.
[http://dx.doi.org/10.1080/13543784.2020.1814252] [PMID: 32853086]
[87]
Charvin, D.; Medori, R.; Hauser, R.A.; Rascol, O. Therapeutic strategies for Parkinson disease: Beyond dopaminergic drugs. Nat. Rev. Drug Discov., 2018, 17(11), 804-822.
[http://dx.doi.org/10.1038/nrd.2018.136] [PMID: 30262889]
[88]
Frantz, S. Playing dirty. Nature, 2005, 437(7061), 942-943.
[http://dx.doi.org/10.1038/437942a] [PMID: 16222266]
[89]
Van der Schyf, C.J.; Geldenhuys, W.J. Multimodal drugs and their future for Alzheimer’s and Parkinson’s disease. Int. Rev. Neurobiol., 2011, 100, 107-125.
[http://dx.doi.org/10.1016/B978-0-12-386467-3.00006-6] [PMID: 21971005]
[90]
Paul, J.; Nandhu, M.S.; Kuruvilla, K.P.; Paulose, C.S.; Dopamine, D. Dopamine D1 and D2 receptor subtypes functional regulation in corpus striatum of unilateral rotenone lesioned Parkinson’s rat model: Effect of serotonin, dopamine and norepinephrine. Neurol. Res., 2010, 32(9), 918-924.
[http://dx.doi.org/10.1179/016164110X12700393823417] [PMID: 20887679]
[91]
Factor, S.A. Dopamine agonists. Med. Clin. North Am., 1999, 83(2), 415-443, vi-vii.
[http://dx.doi.org/10.1016/S0025-7125(05)70112-7] [PMID: 10093586]
[92]
Yan, R.; Cai, H.; Cui, Y.; Su, D.; Cai, G.; Lin, F.; Feng, T. Comparative efficacy and safety of monoamine oxidase type B inhibitors plus channel blockers and monoamine oxidase type B inhibitors as adjuvant therapy to levodopa in the treatment of Parkinson’s disease: A network meta-analysis of randomized controlled trials. Eur. J. Neurol., 2023, 30(4), 1118-1134.
[PMID: 36437702]
[93]
Stocchi, F.; Antonini, A.; Berg, D.; Bergmans, B.; Jost, W.; Katzenschlager, R.; Kulisevsky, J.; Odin, P.; Valldeoriola, F.; Ray Chaudhuri, K. Safinamide in the treatment pathway of Parkinson’s Disease: A European Delphi Consensus. NPJ Parkinsons Dis., 2022, 8(1), 17.
[http://dx.doi.org/10.1038/s41531-022-00277-z] [PMID: 35190544]
[94]
Abbruzzese, G.; Barone, P.; Lopiano, L.; Stocchi, F. The current evidence for the use of safinamide for the treatment of Parkinson’s disease. Drug Des. Devel. Ther., 2021, 15, 2507-2517.
[http://dx.doi.org/10.2147/DDDT.S302673] [PMID: 34140766]
[95]
Gardoni, F.; Morari, M.; Kulisevsky, J.; Brugnoli, A.; Novello, S.; Pisanò, C.A.; Caccia, C.; Mellone, M.; Melloni, E.; Padoani, G.; Sosti, V.; Vailati, S.; Keywood, C. Safinamide modulates striatal glutamatergic signaling in a rat model of levodopa-induced dyskinesia. J. Pharmacol. Exp. Ther., 2018, 367(3), 442-451.
[http://dx.doi.org/10.1124/jpet.118.251645] [PMID: 30291173]
[96]
Pisanò, C.A.; Brugnoli, A.; Novello, S.; Caccia, C.; Keywood, C.; Melloni, E.; Vailati, S.; Padoani, G.; Morari, M. Safinamide inhibits in vivo glutamate release in a rat model of Parkinson’s disease. Neuropharmacology, 2020, 167, 108006.
[http://dx.doi.org/10.1016/j.neuropharm.2020.108006] [PMID: 32086070]
[97]
Sciaccaluga, M.; Mazzocchetti, P.; Bastioli, G.; Ghiglieri, V.; Cardinale, A.; Mosci, P.; Caccia, C.; Keywood, C.; Melloni, E.; Padoani, G.; Vailati, S.; Picconi, B.; Calabresi, P.; Tozzi, A. Effects of safinamide on the glutamatergic striatal network in experimental Parkinson’s disease. Neuropharmacology, 2020, 170, 108024.
[http://dx.doi.org/10.1016/j.neuropharm.2020.108024] [PMID: 32142791]
[98]
Grégoire, L.; Jourdain, V.A.; Townsend, M.; Roach, A.; Di Paolo, T. Safinamide reduces dyskinesias and prolongs l-DOPA antiparkinsonian effect in parkinsonian monkeys. Parkinsonism Relat. Disord., 2013, 19(5), 508-514.
[http://dx.doi.org/10.1016/j.parkreldis.2013.01.009] [PMID: 23402994]
[99]
Grigoriou, S.; Martínez-Martín, P.; Ray Chaudhuri, K.; Rukavina, K.; Leta, V.; Hausbrand, D.; Falkenburger, B.; Odin, P.; Reichmann, H. Effects of safinamide on pain in patients with fluctuating Parkinson’s disease. Brain Behav., 2021, 11(10), e2336.
[http://dx.doi.org/10.1002/brb3.2336] [PMID: 34478245]
[100]
Li, C.; Xue, L.; Liu, Y.; Yang, Z.; Chi, S.; Xie, A. Zonisamide for the treatment of Parkinson disease: A current update. Front. Neurosci., 2020, 14, 574652.
[http://dx.doi.org/10.3389/fnins.2020.574652] [PMID: 33408605]
[101]
Oki, M.; Kaneko, S.; Morise, S.; Takenouchi, N.; Hashizume, T.; Tsuge, A.; Nakamura, M.; Wate, R.; Kusaka, H. Zonisamide ameliorates levodopa-induced dyskinesia and reduces expression of striatal genes in Parkinson model rats. Neurosci. Res., 2017, 122, 45-50.
[http://dx.doi.org/10.1016/j.neures.2017.04.003] [PMID: 28577977]
[102]
Murata, M.; Hasegawa, K.; Kanazawa, I.; Fukasaka, J.; Kochi, K.; Shimazu, R. Zonisamide improves wearing-off in Parkinson’s disease: A randomized, double-blind study. Mov. Disord., 2015, 30(10), 1343-1350.
[http://dx.doi.org/10.1002/mds.26286] [PMID: 26094993]
[103]
Chang, C.; Ramphul, K. Amantadine. In: StatPearls; StatPearls Publishing: Treasure Island, FL, 2023.
[104]
Hauser, R.A.; Lytle, J.; Formella, A.E.; Tanner, C.M. Amantadine delayed release/extended release capsules significantly reduce OFF time in Parkinson’s disease. NPJ Parkinsons Dis., 2022, 8(1), 29.
[http://dx.doi.org/10.1038/s41531-022-00291-1] [PMID: 35304480]
[105]
Araújo, R.; Aranda-Martínez, J.D.; Aranda-Abreu, G.E. Amantadine treatment for people with COVID-19. Arch. Med. Res., 2020, 51(7), 739-740.
[http://dx.doi.org/10.1016/j.arcmed.2020.06.009] [PMID: 32571606]
[106]
Wesnes, K.A.; Aarsland, D.; Ballard, C.; Londos, E. Memantine improves attention and episodic memory in Parkinson’s disease dementia and dementia with Lewy bodies. Int. J. Geriatr. Psychiatry, 2015, 30(1), 46-54.
[http://dx.doi.org/10.1002/gps.4109] [PMID: 24737460]
[107]
Wang, H.F.; Yu, J.T.; Tang, S.W.; Jiang, T.; Tan, C.C.; Meng, X.F.; Wang, C.; Tan, M.S.; Tan, L. Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies: Systematic review with meta-analysis and trial sequential analysis. J. Neurol. Neurosurg. Psychiatry, 2015, 86(2), 135-143.
[http://dx.doi.org/10.1136/jnnp-2014-307659] [PMID: 24828899]
[108]
Seppi, K.; Weintraub, D.; Coelho, M.; Perez-Lloret, S.; Fox, S.H.; Katzenschlager, R.; Hametner, E.M.; Poewe, W.; Rascol, O.; Goetz, C.G.; Sampaio, C. The movement disorder society evidence-based medicine review update: Treatments for the non-motor symptoms of Parkinson’s disease. Mov. Disord., 2011, 26(S3), S42-S80.
[http://dx.doi.org/10.1002/mds.23884] [PMID: 22021174]
[109]
Trifonova, O.P.; Maslov, D.L.; Balashova, E.E.; Urazgildeeva, G.R.; Abaimov, D.A.; Fedotova, E.Y.; Poleschuk, V.V.; Illarioshkin, S.N.; Lokhov, P.G. Parkinson’s Disease: Available clinical and promising omics tests for diagnostics, disease risk assessment, and pharmacotherapy personalization. Diagnostics, 2020, 10(5), 339.
[http://dx.doi.org/10.3390/diagnostics10050339] [PMID: 32466249]
[110]
Teshuva, I.; Hillel, I.; Gazit, E.; Giladi, N.; Mirelman, A.; Hausdorff, J.M. Using wearables to assess bradykinesia and rigidity in patients with Parkinson’s disease: A focused, narrative review of the literature. J. Neural Transm., 2019, 126(6), 699-710.
[http://dx.doi.org/10.1007/s00702-019-02017-9] [PMID: 31115669]
[111]
van Wamelen, D.J.; Sringean, J.; Trivedi, D.; Carroll, C.B.; Schrag, A.E.; Odin, P.; Antonini, A.; Bloem, B.R.; Bhidayasiri, R.; Chaudhuri, K.R. Digital health technology for non-motor symptoms in people with Parkinson’s disease: Futile or future? Parkinsonism Relat. Disord., 2021, 89, 186-194.
[http://dx.doi.org/10.1016/j.parkreldis.2021.07.032] [PMID: 34362670]
[112]
van Wamelen, D.J.; Martinez-Martin, P.; Weintraub, D.; Schrag, A.; Antonini, A.; Falup-Pecurariu, C.; Odin, P.; Ray Chaudhuri, K. The Non‐Motor Symptoms Scale in Parkinson’s disease: Validation and use. Acta Neurol. Scand., 2021, 143(1), 3-12.
[http://dx.doi.org/10.1111/ane.13336] [PMID: 32813911]
[113]
Qureshi, A.R.; Rana, A.Q.; Malik, S.H.; Rizvi, S.F.H.; Akhter, S.; Vannabouathong, C.; Sarfraz, Z.; Rana, R. Comprehensive examination of therapies for pain in Parkinson’s disease: A systematic review and meta-analysis. Neuroepidemiology, 2018, 51(3-4), 190-206.
[http://dx.doi.org/10.1159/000492221] [PMID: 30153669]
[114]
Sharaf, J.; Williams, K.A.D.; Tariq, M.; Acharekar, M.V.; Guerrero Saldivia, S.E.; Unnikrishnan, S.; Chavarria, Y.Y.; Akindele, A.O.; Jalkh, A.P.; Eastmond, A.K.; Shetty, C.; Rizvi, S.M.H.A.; Mohammed, L. The efficacy of safinamide in the management of Parkinson’s disease: A systematic review. Cureus, 2022, 14(9), e29118.
[http://dx.doi.org/10.7759/cureus.29118] [PMID: 36259026]
[115]
Dulski, J.; Uitti, R.J.; Ross, O.A.; Wszolek, Z.K. Genetic architecture of Parkinson’s disease subtypes-review of the literature. Front. Aging Neurosci., 2022, 14, 1023574.
[http://dx.doi.org/10.3389/fnagi.2022.1023574] [PMID: 36337703]
[116]
Rodriguez-Sanchez, F.; Rodriguez-Blazquez, C.; Bielza, C.; Larrañaga, P.; Weintraub, D.; Martinez-Martin, P.; Rizos, A.; Schrag, A.; Chaudhuri, K.R. Identifying Parkinson’s disease subtypes with motor and non-motor symptoms via model-based multi-partition clustering. Sci. Rep., 2021, 11(1), 23645.
[http://dx.doi.org/10.1038/s41598-021-03118-w] [PMID: 34880345]
[117]
Huang, X.; Ng, S.Y.E.; Chia, N.S.Y.; Setiawan, F.; Tay, K.Y.; Au, W.L.; Tan, E.K.; Tan, L.C.S. Non-motor symptoms in early Parkinson’s disease with different motor subtypes and their associations with quality of life. Eur. J. Neurol., 2019, 26(3), 400-406.
[http://dx.doi.org/10.1111/ene.13803] [PMID: 30175887]
[118]
Zhang, X.; Chou, J.; Liang, J.; Xiao, C.; Zhao, Y.; Sarva, H.; Henchcliffe, C.; Wang, F. Data-driven subtyping of parkinson’s disease using longitudinal clinical records: A cohort study. Sci. Rep., 2019, 9(1), 797.
[http://dx.doi.org/10.1038/s41598-018-37545-z] [PMID: 30692568]
[119]
Marras, C.; Chaudhuri, K.R.; Titova, N.; Mestre, T.A. Therapy of Parkinson’s disease subtypes. Neurotherapeutics, 2020, 17(4), 1366-1377.
[http://dx.doi.org/10.1007/s13311-020-00894-7] [PMID: 32749651]
[120]
Langston, J.W. The parkinson’s complex: Parkinsonism is just the tip of the iceberg. Ann. Neurol., 2006, 59(4), 591-596.
[http://dx.doi.org/10.1002/ana.20834] [PMID: 16566021]
[121]
Titova, N.; Padmakumar, C.; Lewis, S.J.G.; Chaudhuri, K.R. Parkinson’s: A syndrome rather than a disease? J. Neural Transm., 2017, 124(8), 907-914.
[http://dx.doi.org/10.1007/s00702-016-1667-6] [PMID: 28028643]
[122]
Hirsch, E.C.; Graybiel, A.M.; Duyckaerts, C.; Javoy-Agid, F. Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc. Natl. Acad. Sci. USA, 1987, 84(16), 5976-5980.
[http://dx.doi.org/10.1073/pnas.84.16.5976] [PMID: 3475716]
[123]
Jellinger, K. Overview of morphological changes in Parkinson’s disease. Adv. Neurol., 1987, 45, 1-18.
[PMID: 3825687]
[124]
Halliday, G.M.; Blumbergs, P.C.; Cotton, R.G.H.; Blessing, W.W.; Geffen, L.B. Loss of brainstem serotonin- and substance P-containing neurons in Parkinson’s disease. Brain Res., 1990, 510(1), 104-107.
[http://dx.doi.org/10.1016/0006-8993(90)90733-R] [PMID: 1691042]
[125]
Weintraub, D.; Simuni, T.; Caspell-Garcia, C.; Coffey, C.; Lasch, S.; Siderowf, A.; Aarsland, D.; Barone, P.; Burn, D.; Chahine, L.M.; Eberling, J.; Espay, A.J.; Foster, E.D.; Leverenz, J.B.; Litvan, I.; Richard, I.; Troyer, M.D.; Hawkins, K.A. Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson’s disease. Mov. Disord., 2015, 30(7), 919-927.
[http://dx.doi.org/10.1002/mds.26170] [PMID: 25737166]
[126]
Gjerløff, T.; Fedorova, T.; Knudsen, K.; Munk, O.L.; Nahimi, A.; Jacobsen, S.; Danielsen, E.H.; Terkelsen, A.J.; Hansen, J.; Pavese, N.; Brooks, D.J.; Borghammer, P. Imaging acetylcholinesterase density in peripheral organs in Parkinson’s disease with 11C-donepezil PET. Brain, 2015, 138(3), 653-663.
[http://dx.doi.org/10.1093/brain/awu369] [PMID: 25539902]
[127]
O’Callaghan, C.; Lewis, S.J.G. Cognition in Parkinson’s disease. Int. Rev. Neurobiol., 2017, 133, 557-583.
[http://dx.doi.org/10.1016/bs.irn.2017.05.002] [PMID: 28802933]
[128]
Pavese, N.; Metta, V.; Bose, S.K.; Chaudhuri, K.R.; Brooks, D.J. Fatigue in Parkinson’s disease is linked to striatal and limbic serotonergic dysfunction. Brain, 2010, 133(11), 3434-3443.
[http://dx.doi.org/10.1093/brain/awq268] [PMID: 20884645]
[129]
Svenningsson, P.; Odin, P.; Dizdar, N.; Johansson, A.; Grigoriou, S.; Tsitsi, P.; Wictorin, K.; Bergquist, F.; Nyholm, D.; Rinne, J.; Hansson, F.; Sonesson, C.; Tedroff, J.; Andersson, K.; Sundgren, M.; Duzynski, W.; Carlström, C. A phase 2a trial investigating the safety and tolerability of the novel cortical enhancer IRL752 in Parkinson’s disease dementia. Mov. Disord., 2020, 35(6), 1046-1054.
[http://dx.doi.org/10.1002/mds.28020] [PMID: 32198802]
[130]
Horsager, J.; Okkels, N.; Hansen, A.K.; Damholdt, M.F.; Andersen, K.H.; Fedorova, T.D.; Munk, O.L.; Danielsen, E.H.; Pavese, N.; Brooks, D.J.; Borghammer, P. Mapping cholinergic synaptic loss in Parkinson’s Disease: An [18F]FEOBV PET case-control study. J. Parkinsons Dis., 2022, 12(8), 2493-2506.
[http://dx.doi.org/10.3233/JPD-223489] [PMID: 36336941]
[131]
Wang, X.L.; Feng, S.T.; Wang, Y.T.; Chen, B.; Wang, Z.Z.; Chen, N.H.; Zhang, Y. Comparative efficacy and acceptability of drug treatments for Parkinson’s disease with depression: A systematic review with network meta-analysis. Eur. J. Pharmacol., 2022, 927, 175070.
[http://dx.doi.org/10.1016/j.ejphar.2022.175070] [PMID: 35659968]
[132]
Bara-Jimenez, W.; Bibbiani, F.; Morris, M.J.; Dimitrova, T.; Sherzai, A.; Mouradian, M.M.; Chase, T.N. Effects of serotonin 5-HT1A agonist in advanced Parkinson’s disease. Mov. Disord., 2005, 20(8), 932-936.
[http://dx.doi.org/10.1002/mds.20370] [PMID: 15791634]
[133]
Bibbiani, F.; Oh, J.D.; Chase, T.N. Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. Neurology, 2001, 57(10), 1829-1834.
[http://dx.doi.org/10.1212/WNL.57.10.1829] [PMID: 11723272]
[134]
Bonifati, V.; Fabrizio, E.; Cipriani, R.; Vanacore, N.; Meco, G. Buspirone in levodopa-induced dyskinesias. Clin. Neuropharmacol., 1994, 17(1), 73-82.
[http://dx.doi.org/10.1097/00002826-199402000-00008] [PMID: 8149361]
[135]
Hsam, O.; Kohl, Z. Serotonin in synucleinopathies. Behav. Brain Res., 2023, 445, 114367.
[http://dx.doi.org/10.1016/j.bbr.2023.114367] [PMID: 36863462]
[136]
Shan, L.; Hofman, M.A.; van Wamelen, D.J.; Van Someren, E.J.W.; Bao, A.M.; Swaab, D.F. Diurnal fluctuation in histidine decarboxylase expression, the rate limiting enzyme for histamine production, and its disorder in neurodegenerative diseases. Sleep, 2012, 35(5), 713-715.
[http://dx.doi.org/10.5665/sleep.1838] [PMID: 22547898]
[137]
van Wamelen, D.J.; Shan, L.; Aziz, N.A.; Anink, J.J.; Bao, A.M.; Roos, R.A.C.; Swaab, D.F. Functional increase of brain histaminergic signaling in Huntington’s disease. Brain Pathol., 2011, 21(4), 419-427.
[http://dx.doi.org/10.1111/j.1750-3639.2010.00465.x] [PMID: 21106039]
[138]
Alhusaini, M.; Eissa, N.; Saad, A.K.; Beiram, R.; Sadek, B. Revisiting preclinical observations of several Histamine H3 Receptor antagonists/inverse agonists in cognitive impairment, anxiety, depression, and sleep-wake cycle disorder. Front. Pharmacol., 2022, 13, 861094.
[http://dx.doi.org/10.3389/fphar.2022.861094] [PMID: 35721194]
[139]
Nowak, P.; Noras, Ł.; Jochem, J.; Szkilnik, R.; Brus, H.; Körőssy, E.; Drab, J.; Kostrzewa, R.M.; Brus, R. Histaminergic activity in a rodent model of Parkinson’s disease. Neurotox. Res., 2009, 15(3), 246-251.
[http://dx.doi.org/10.1007/s12640-009-9025-1] [PMID: 19384597]
[140]
Masini, D.; Lopes-Aguiar, C.; Bonito-Oliva, A.; Papadia, D.; Andersson, R.; Fisahn, A.; Fisone, G. The histamine H3 receptor antagonist thioperamide rescues circadian rhythm and memory function in experimental parkinsonism. Transl. Psychiatry, 2017, 7(4), e1088.
[http://dx.doi.org/10.1038/tp.2017.58] [PMID: 28398338]
[141]
Rekha, K.R.; Selvakumar, G.P.; Santha, K.; Inmozhi Sivakamasundari, R. Geraniol attenuates α-synuclein expression and neuromuscular impairment through increase dopamine content in MPTP intoxicated mice by dose dependent manner. Biochem. Biophys. Res. Commun., 2013, 440(4), 664-670.
[http://dx.doi.org/10.1016/j.bbrc.2013.09.122] [PMID: 24103762]
[142]
Rekha, K.R.; Selvakumar, G.P.; Sethupathy, S.; Santha, K.; Sivakamasundari, R.I. Geraniol ameliorates the motor behavior and neurotrophic factors inadequacy in MPTP-induced mice model of Parkinson’s disease. J. Mol. Neurosci., 2013, 51(3), 851-862.
[http://dx.doi.org/10.1007/s12031-013-0074-9] [PMID: 23943375]
[143]
Titova, N.; Chaudhuri, K.R. Nonmotor parkinson’s and future directions. Int. Rev. Neurobiol., 2017, 134, 1493-1505.
[http://dx.doi.org/10.1016/bs.irn.2017.05.017] [PMID: 28805581]
[144]
Zetusky, W.J.; Jankovic, J.; Pirozzolo, F.J. The heterogeneity of Parkinson’s disease: Clinical and prognostic implications. Neurology, 1985, 35(4), 522-526.
[http://dx.doi.org/10.1212/WNL.35.4.522] [PMID: 3982637]
[145]
Jankovic, J.; McDermott, M.; Carter, J.; Gauthier, S.; Goetz, C.; Golbe, L.; Huber, S.; Koller, W.; Olanow, C.; Shoulson, I.; Stern, M.; Tanner, C.; Weiner, W. Variable expression of Parkinson’s disease: A base-line analysis of the DAT ATOP cohort. Neurology, 1990, 40(10), 1529-1534.
[http://dx.doi.org/10.1212/WNL.40.10.1529] [PMID: 2215943]
[146]
Schiess, M.C.; Zheng, H.; Soukup, V.M.; Bonnen, J.G.; Nauta, H.J.W. Parkinson’s disease subtypes: Clinical classification and ventricular cerebrospinal fluid analysis. Parkinsonism Relat. Disord., 2000, 6(2), 69-76.
[http://dx.doi.org/10.1016/S1353-8020(99)00051-6] [PMID: 10699387]
[147]
Korchounov, A.; Schipper, H.I.; Preobrazhenskaya, I.S.; Kessler, K.R.; Yakhno, N.N. Differences in age at onset and familial aggregation between clinical types of idiopathic Parkinson’s disease. Mov. Disord., 2004, 19(9), 1059-1064.
[http://dx.doi.org/10.1002/mds.20061] [PMID: 15372596]
[148]
Kang, G.A.; Bronstein, J.M.; Masterman, D.L.; Redelings, M.; Crum, J.A.; Ritz, B. Clinical characteristics in early Parkinson’s disease in a central California population-based study. Mov. Disord., 2005, 20(9), 1133-1142.
[http://dx.doi.org/10.1002/mds.20513] [PMID: 15954133]
[149]
Konno, T.; Deutschländer, A.; Heckman, M.G.; Ossi, M.; Vargas, E.R.; Strongosky, A.J.; van Gerpen, J.A.; Uitti, R.J.; Ross, O.A.; Wszolek, Z.K. Comparison of clinical features among Parkinson’s disease subtypes: A large retrospective study in a single center. J. Neurol. Sci., 2018, 386, 39-45.
[http://dx.doi.org/10.1016/j.jns.2018.01.013] [PMID: 29406964]
[150]
Lawton, M.; Ben-Shlomo, Y.; May, M.T.; Baig, F.; Barber, T.R.; Klein, J.C.; Swallow, D.M.A.; Malek, N.; Grosset, K.A.; Bajaj, N.; Barker, R.A.; Williams, N.; Burn, D.J.; Foltynie, T.; Morris, H.R.; Wood, N.W.; Grosset, D.G.; Hu, M.T.M. Developing and validating Parkinson’s disease subtypes and their motor and cognitive progression. J. Neurol. Neurosurg. Psychiatry, 2018, 89(12), 1279-1287.
[http://dx.doi.org/10.1136/jnnp-2018-318337] [PMID: 30464029]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy