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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Mini-Review Article

Tackling Neuroinflammation in Cognitive Disorders with Single-targeted and Multi-targeted Histamine H3 Receptor Modulators

Author(s): Flávia Barrio Lopes, João Paulo S. Fernandes* and Elisa Uliassi*

Volume 24, Issue 28, 2024

Published on: 23 August, 2024

Page: [2421 - 2430] Pages: 10

DOI: 10.2174/0115680266322294240816051818

Price: $65

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Abstract

Neuroinflammation is a process involved in a variety of central nervous system (CNS) diseases and is being increasingly recognized as a key mediator of cognitive impairments. Neuroinflammatory responses including glial activation, increased production of proinflammatory cytokines, and aberrant neuronal signaling, contribute to cognitive dysfunctions. Histamine is a key peripheral inflammatory mediator, but plays an important role in neuroinflammatory processes as well. The unique localization of histamine H3 receptor (H3R) in the CNS along with the modulation of the release of other neurotransmitters via its action on heteroreceptors on non-histaminergic neurons have led to the development of several H3R ligands for various brain diseases. H3R antagonists/ inverse agonists have revealed potential to treat diverse neuroinflammatory CNS disorders, including neurodegenerative diseases, attention-deficit hyperactivity syndrome and schizophrenia. In this mini review, we provide a brief overview on the crucial involvement of the histaminergic transmission in the neuroinflammatory processes underlying these cognitive disorders, with a special focus on H3R involvement. The anti-neuroinflammatory potential of single-targeted and multi-targeted H3R antagonists/inverse agonists for the treatment of these conditions is discussed here.

Keywords: Neuroinflammation, Cognitive disorders, Histamine H3 receptor, Neurodegenerative disease, Multi-target compounds, Central nervous system.

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[1]
Kwon, H.S.; Koh, S.H. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Transl. Neurodegener., 2020, 9(1), 42.
[http://dx.doi.org/10.1186/s40035-020-00221-2] [PMID: 33239064]
[2]
Carthy, E.; Ellender, T. Histamine, Neuroinflammation and Neurodevelopment: A Review. Front. Neurosci., 2021, 15, 680214.
[http://dx.doi.org/10.3389/fnins.2021.680214] [PMID: 34335160]
[3]
Eissa, N.; Sadeq, A.; Sasse, A.; Sadek, B. Role of neuroinflammation in autism spectrum disorder and the emergence of brain histaminergic system. Lessons also for BPSD? Front. Pharmacol., 2020, 11, 886.
[http://dx.doi.org/10.3389/fphar.2020.00886] [PMID: 32612529]
[4]
Wilson, D.M., III; Cookson, M.R.; Van Den Bosch, L.; Zetterberg, H.; Holtzman, D.M.; Dewachter, I. Hallmarks of neurodegenerative diseases. Cell, 2023, 186(4), 693-714.
[http://dx.doi.org/10.1016/j.cell.2022.12.032] [PMID: 36803602]
[5]
Heneka, M.T.; Carson, M.J.; Khoury, J.E.; Landreth, G.E.; Brosseron, F.; Feinstein, D.L.; Jacobs, A.H.; Wyss-Coray, T.; Vitorica, J.; Ransohoff, R.M.; Herrup, K.; Frautschy, S.A.; Finsen, B.; Brown, G.C.; Verkhratsky, A.; Yamanaka, K.; Koistinaho, J.; Latz, E.; Halle, A.; Petzold, G.C.; Town, T.; Morgan, D.; Shinohara, M.L.; Perry, V.H.; Holmes, C.; Bazan, N.G.; Brooks, D.J.; Hunot, S.; Joseph, B.; Deigendesch, N.; Garaschuk, O.; Boddeke, E.; Dinarello, C.A.; Breitner, J.C.; Cole, G.M.; Golenbock, D.T.; Kummer, M.P. Neuroinflammation in Alzheimer’s disease. Lancet Neurol., 2015, 14(4), 388-405.
[http://dx.doi.org/10.1016/S1474-4422(15)70016-5] [PMID: 25792098]
[6]
Ransohoff, R.M. How neuroinflammation contributes to neurodegeneration. Science, 2016, 353(6301), 777-783.
[http://dx.doi.org/10.1126/science.aag2590] [PMID: 27540165]
[7]
Wendimu, M.Y.; Hooks, S.B. Microglia phenotypes in aging and neurodegenerative diseases. Cells, 2022, 11(13), 2091.
[http://dx.doi.org/10.3390/cells11132091] [PMID: 35805174]
[8]
Wang, W-Y.; Tan, M-S.; Yu, J-T.; Tan, L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann. Transl. Med., 2015, 3(10), 136.
[PMID: 26207229]
[9]
Brodacki, B.; Staszewski, J.; Toczyłowska, B.; Kozłowska, E.; Drela, N.; Chalimoniuk, M.; Stępien, A. Serum interleukin (IL-2, IL-10, IL-6, IL-4), TNFα, and INFγ concentrations are elevated in patients with atypical and idiopathic parkinsonism. Neurosci. Lett., 2008, 441(2), 158-162.
[http://dx.doi.org/10.1016/j.neulet.2008.06.040] [PMID: 18582534]
[10]
Zhuo, C.; Tian, H.; Song, X.; Jiang, D.; Chen, G.; Cai, Z.; Ping, J.; Cheng, L.; Zhou, C.; Chen, C. Microglia and cognitive impairment in schizophrenia: Translating scientific progress into novel therapeutic interventions. Schizophrenia, 2023, 9(1), 42.
[http://dx.doi.org/10.1038/s41537-023-00370-z] [PMID: 37429882]
[11]
Peña-Altamira, E.; Prati, F.; Massenzio, F.; Virgili, M.; Contestabile, A.; Bolognesi, M.L.; Monti, B. Changing paradigm to target microglia in neurodegenerative diseases: From anti-inflammatory strategy to active immunomodulation. Expert Opin. Ther. Targets, 2016, 20(5), 627-640.
[http://dx.doi.org/10.1517/14728222.2016.1121237] [PMID: 26568363]
[12]
Imbimbo, B.P.; Solfrizzi, V.; Panza, F. Are NSAIDs useful to treat Alzheimer’s disease or mild cognitive impairment? Front. Aging Neurosci., 2010, 2, 2.
[http://dx.doi.org/10.3389/fnagi.2010.00019] [PMID: 20725517]
[13]
Fu, W.Y.; Wang, X.; Ip, N.Y. Targeting neuroinflammation as a therapeutic strategy for alzheimer’s disease: Mechanisms, drug candidates, and new opportunities. ACS Chem. Neurosci., 2019, 10(2), 872-879.
[http://dx.doi.org/10.1021/acschemneuro.8b00402] [PMID: 30221933]
[14]
Cummings, J.; Zhou, Y.; Lee, G.; Zhong, K.; Fonseca, J.; Cheng, F. Alzheimer’s disease drug development pipeline: 2023. Alzheimers Dement. (N. Y.), 2023, 9(2), e12385.
[http://dx.doi.org/10.1002/trc2.12385] [PMID: 37251912]
[15]
Branco, A.C.C.C.; Yoshikawa, F.S.Y.; Pietrobon, A.J.; Sato, M.N. Role of Histamine in Modulating the Immune Response and Inflammation. Mediators Inflamm., 2018, 2018, 1-10.
[http://dx.doi.org/10.1155/2018/9524075] [PMID: 30224900]
[16]
Panula, P.; Nuutinen, S. The histaminergic network in the brain: Basic organization and role in disease. Nat. Rev. Neurosci., 2013, 14(7), 472-487.
[http://dx.doi.org/10.1038/nrn3526] [PMID: 23783198]
[17]
Provensi, G.; Costa, A.; Izquierdo, I.; Blandina, P.; Passani, M.B. Brain histamine modulates recognition memory: Possible implications in major cognitive disorders. Br. J. Pharmacol., 2020, 177(3), 539-556.
[http://dx.doi.org/10.1111/bph.14478] [PMID: 30129226]
[18]
Yoshikawa, T.; Nakamura, T.; Yanai, K. Histaminergic neurons in the tuberomammillary nucleus as a control centre for wakefulness. Br. J. Pharmacol., 2021, 178(4), 750-769.
[http://dx.doi.org/10.1111/bph.15220] [PMID: 32744724]
[19]
Zlomuzica, A.; Dere, D.; Binder, S.; De Souza Silva, M.A.; Huston, J.P.; Dere, E. Neuronal histamine and cognitive symptoms in Alzheimer’s disease. Neuropharmacology, 2016, 106, 135-145.
[http://dx.doi.org/10.1016/j.neuropharm.2015.05.007] [PMID: 26025658]
[20]
Correa, M.F.; Fernandes, J.P.S. QSAR Modeling of Histamine H3R Antagonists/inverse Agonists as Future Drugs for Neurodegenerative Diseases. Curr. Neuropharmacol., 2018, 16(6), 749-757.
[http://dx.doi.org/10.2174/1570159X15666170818100644] [PMID: 28820054]
[21]
Lopes, F.B.; Aranha, C.M.S.Q.; Fernandes, J.P.S. Histamine H 3 receptor and cholinesterases as synergistic targets for cognitive decline: Strategies to the rational design of multitarget ligands. Chem. Biol. Drug Des., 2021, 98(2), 212-225.
[http://dx.doi.org/10.1111/cbdd.13866] [PMID: 33991182]
[22]
Nieto-Alamilla, G.; Márquez-Gómez, R.; García-Gálvez, A.M.; Morales-Figueroa, G.E.; Arias-Montaño, J.A. The Histamine H 3 Receptor: Structure, pharmacology, and function. Mol. Pharmacol., 2016, 90(5), 649-673.
[http://dx.doi.org/10.1124/mol.116.104752] [PMID: 27563055]
[23]
Ellenbroek, B.A.; Ghiabi, B. The other side of the histamine H3 receptor. Trends Neurosci., 2014, 37(4), 191-199.
[http://dx.doi.org/10.1016/j.tins.2014.02.007] [PMID: 24636456]
[24]
Zheng, Y.; Fan, L.; Fang, Z.; Liu, Z.; Chen, J.; Zhang, X.; Wang, Y.; Zhang, Y.; Jiang, L.; Chen, Z.; Hu, W. Postsynaptic histamine H3 receptors in ventral basal forebrain cholinergic neurons modulate contextual fear memory. Cell Rep., 2023, 42(9), 113073.
[http://dx.doi.org/10.1016/j.celrep.2023.113073] [PMID: 37676764]
[25]
Sadek, B.; Saad, A.; Sadeq, A.; Jalal, F.; Stark, H. Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases. Behav. Brain Res., 2016, 312, 415-430.
[http://dx.doi.org/10.1016/j.bbr.2016.06.051] [PMID: 27363923]
[26]
Kubo, M.; Kishi, T.; Matsunaga, S.; Iwata, N. Histamine H3 receptor antagonists for alzheimer’s disease: A systematic review and meta-analysis of randomized placebo-controlled trials. J. Alzheimers Dis., 2015, 48(3), 667-671.
[http://dx.doi.org/10.3233/JAD-150393] [PMID: 26402104]
[27]
Correa, M.F.; Fernandes, J.P.S. Targeting the Histamine H4 Receptor: Future Drugs for Inflammatory Diseases. Curr. Org. Chem., 2018, 22(17), 1663-1672.
[http://dx.doi.org/10.2174/1385272822666180710144636]
[28]
Schirmer, B.; Neumann, D. The Function of the Histamine H4 Receptor in Inflammatory and Inflammation-Associated Diseases of the Gut. Int. J. Mol. Sci., 2021, 22(11), 6116.
[http://dx.doi.org/10.3390/ijms22116116] [PMID: 34204101]
[29]
Mehta, P.; Miszta, P.; Rzodkiewicz, P.; Michalak, O.; Krzeczyński, P.; Filipek, S. Enigmatic Histamine Receptor H4 for Potential Treatment of Multiple Inflammatory, Autoimmune, and Related Diseases. Life (Basel), 2020, 10(4), 50.
[http://dx.doi.org/10.3390/life10040050] [PMID: 32344736]
[30]
Ferreira, R.; Santos, T.; Gonçalves, J.; Baltazar, G.; Ferreira, L.; Agasse, F.; Bernardino, L. Histamine modulates microglia function. J. Neuroinflammation, 2012, 9(1), 90.
[http://dx.doi.org/10.1186/1742-2094-9-90] [PMID: 22569158]
[31]
Zhang, W.; Zhang, X.; Zhang, Y.; Qu, C.; Zhou, X.; Zhang, S. Histamine induces microglia activation and the release of proinflammatory mediators in rat brain via H1R or H4R. J. Neuroimmune Pharmacol., 2020, 15(2), 280-291.
[http://dx.doi.org/10.1007/s11481-019-09887-6] [PMID: 31863333]
[32]
Rocha, S.M.; Saraiva, T.; Cristóvão, A.C.; Ferreira, R.; Santos, T.; Esteves, M.; Saraiva, C.; Je, G.; Cortes, L.; Valero, J.; Alves, G.; Klibanov, A.; Kim, Y.S.; Bernardino, L. Histamine induces microglia activation and dopaminergic neuronal toxicity via H1 receptor activation. J. Neuroinflammation, 2016, 13(1), 137.
[http://dx.doi.org/10.1186/s12974-016-0600-0] [PMID: 27260166]
[33]
Cacabelos, R.; Torrellas, C.; Fernández-Novoa, L.; Aliev, G. Neuroimmune crosstalk in CNS disorders: The histamine connection. Curr. Pharm. Des., 2016, 22(7), 819-848.
[http://dx.doi.org/10.2174/1381612822666151209150954] [PMID: 26648474]
[34]
Cacabelos, R.; Torrellas, C.; Fernández-Novoa, L.; López-Muñoz, F. Histamine and immune biomarkers in CNS disorders. Mediators Inflamm., 2016, 2016, 1-10.
[http://dx.doi.org/10.1155/2016/1924603] [PMID: 27190492]
[35]
Jurič, D.M.; Kržan, M.; Lipnik-Stangelj, M. Histamine and astrocyte function. Pharmacol. Res., 2016, 111, 774-783.
[http://dx.doi.org/10.1016/j.phrs.2016.07.035] [PMID: 27475882]
[36]
Xu, J.; Zhang, X.; Qian, Q.; Wang, Y.; Dong, H.; Li, N.; Qian, Y.; Jin, W. Histamine upregulates the expression of histamine receptors and increases the neuroprotective effect of astrocytes. J. Neuroinflammation, 2018, 15(1), 41.
[http://dx.doi.org/10.1186/s12974-018-1068-x] [PMID: 29433511]
[37]
Berlin, M.; Boyce, C.W.; de Lera Ruiz, M. Histamine H3 receptor as a drug discovery target. J. Med. Chem., 2011, 54(1), 26-53.
[http://dx.doi.org/10.1021/jm100064d] [PMID: 21062081]
[38]
Peng, X.; Yang, L.; Liu, Z.; Lou, S.; Mei, S.; Li, M.; Chen, Z.; Zhang, H. Structural basis for recognition of antihistamine drug by human histamine receptor. Nat. Commun., 2022, 13(1), 6105.
[http://dx.doi.org/10.1038/s41467-022-33880-y] [PMID: 36243875]
[39]
Lamb, Y.N. Pitolisant: A review in narcolepsy with or without cataplexy. CNS Drugs, 2020, 34(2), 207-218.
[http://dx.doi.org/10.1007/s40263-020-00703-x] [PMID: 31997137]
[40]
Pullen, L.C.; Picone, M.; Tan, L.; Johnston, C.; Stark, H. Cognitive improvements in children with prader-willi syndrome following pitolisant treatment—patient reports. J. Pediatr. Pharmacol. Ther., 2019, 24(2), 166-171.
[http://dx.doi.org/10.5863/1551-6776-24.2.166] [PMID: 31019411]
[41]
Medhurst, A.D.; Atkins, A.R.; Beresford, I.J.; Brackenborough, K.; Briggs, M.A.; Calver, A.R.; Cilia, J.; Cluderay, J.E.; Crook, B.; Davis, J.B.; Davis, R.K.; Davis, R.P.; Dawson, L.A.; Foley, A.G.; Gartlon, J.; Gonzalez, M.I.; Heslop, T.; Hirst, W.D.; Jennings, C.; Jones, D.N.C.; Lacroix, L.P.; Martyn, A.; Ociepka, S.; Ray, A.; Regan, C.M.; Roberts, J.C.; Schogger, J.; Southam, E.; Stean, T.O.; Trail, B.K.; Upton, N.; Wadsworth, G.; Wald, J.A.; White, T.; Witherington, J.; Woolley, M.L.; Worby, A.; Wilson, D.M. GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer’s disease brain and improves cognitive performance in preclinical models. J. Pharmacol. Exp. Ther., 2007, 321(3), 1032-1045.
[http://dx.doi.org/10.1124/jpet.107.120311] [PMID: 17327487]
[42]
Grove, R.; Harrington, C.; Mahler, A.; Beresford, I.; Maruff, P.; Lowy, M.; Nicholls, A.; Boardley, R.; Berges, A.; Nathan, P.; Horrigan, J. A randomized, double-blind, placebo-controlled, 16-week study of the H3 receptor antagonist, GSK239512 as a monotherapy in subjects with mild-to-moderate Alzheimer’s disease. Curr. Alzheimer Res., 2014, 11(1), 47-58.
[http://dx.doi.org/10.2174/1567205010666131212110148] [PMID: 24359500]
[43]
Wilson, D.M.; Apps, J.; Bailey, N.; Bamford, M.J.; Beresford, I.J.; Briggs, M.A.; Calver, A.R.; Crook, B.; Davis, R.P.; Davis, S.; Dean, D.K.; Harris, L.; Heightman, T.D.; Panchal, T.; Parr, C.A.; Quashie, N.; Steadman, J.G.A.; Schogger, J.; Sehmi, S.S.; Stean, T.O.; Takle, A.K.; Trail, B.K.; White, T.; Witherington, J.; Worby, A.; Medhurst, A.D. The discovery of the benzazepine class of histamine H3 receptor antagonists. Bioorg. Med. Chem. Lett., 2013, 23(24), 6897-6901.
[http://dx.doi.org/10.1016/j.bmcl.2013.09.089] [PMID: 24161834]
[44]
Wilson, D.M.; Apps, J.; Bailey, N.; Bamford, M.J.; Beresford, I.J.; Brackenborough, K.; Briggs, M.A.; Brough, S.; Calver, A.R.; Crook, B.; Davis, R.K.; Davis, R.P.; Davis, S.; Dean, D.K.; Harris, L.; Heslop, T.; Holland, V.; Jeffrey, P.; Panchal, T.A.; Parr, C.A.; Quashie, N.; Schogger, J.; Sehmi, S.S.; Stean, T.O.; Steadman, J.G.A.; Trail, B.; Wald, J.; Worby, A.; Takle, A.K.; Witherington, J.; Medhurst, A.D. Identification of clinical candidates from the benzazepine class of histamine H3 receptor antagonists. Bioorg. Med. Chem. Lett., 2013, 23(24), 6890-6896.
[http://dx.doi.org/10.1016/j.bmcl.2013.09.090] [PMID: 24269482]
[45]
Othman, A.A.; Haig, G.; Florian, H.; Locke, C.; Zhang, J.; Dutta, S. Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT -288, in healthy young adults and elderly volunteers. Br. J. Clin. Pharmacol., 2013, 75(5), 1299-1311.
[http://dx.doi.org/10.1111/j.1365-2125.2012.04472.x] [PMID: 23016924]
[46]
Haig, G.M.; Pritchett, Y.; Meier, A.; Othman, A.A.; Hall, C.; Gault, L.M.; Lenz, R.A. A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer’s dementia. J. Alzheimers Dis., 2014, 42(3), 959-971.
[http://dx.doi.org/10.3233/JAD-140291] [PMID: 25024314]
[47]
Haig, G.M.; Bain, E.; Robieson, W.; Othman, A.A.; Baker, J.; Lenz, R.A. A randomized trial of the efficacy and safety of the H3 antagonist ABT-288 in cognitive impairment associated with schizophrenia. Schizophr. Bull., 2014, 40(6), 1433-1442.
[http://dx.doi.org/10.1093/schbul/sbt240] [PMID: 24516190]
[48]
Kim, Y.J.; Goto, Y.; Lee, Y.A. Histamine H3 receptor antagonists ameliorate attention deficit/hyperactivity disorder-like behavioral changes caused by neonatal habenula lesion. Behav. Pharmacol., 2018, 29(1), 71-78.
[http://dx.doi.org/10.1097/FBP.0000000000000343] [PMID: 28863002]
[49]
Fox, G.B.; Pan, J.B.; Esbenshade, T.A.; Bennani, Y.L.; Black, L.A.; Faghih, R.; Hancock, A.A.; Decker, M.W. Effects of histamine H3 receptor ligands GT-2331 and ciproxifan in a repeated acquisition avoidance response in the spontaneously hypertensive rat pup. Behav. Brain Res., 2002, 131(1-2), 151-161.
[http://dx.doi.org/10.1016/S0166-4328(01)00379-5] [PMID: 11844582]
[50]
Weisler, R.H.; Pandina, G.J.; Daly, E.J.; Cooper, K.; Gassmann- Mayer, C. Randomized clinical study of a histamine H3 receptor antagonist for the treatment of adults with attention-deficit hyperactivity disorder. CNS Drugs, 2012, 26(5), 421-434.
[http://dx.doi.org/10.2165/11631990-000000000-00000] [PMID: 22519922]
[51]
Wang, J.; Liu, B.; Xu, Y.; Luan, H.; Wang, C.; Yang, M.; Zhao, R.; Song, M.; Liu, J.; Sun, L.; You, J.; Wang, W.; Sun, F.; Yan, H. Thioperamide attenuates neuroinflammation and cognitive impairments in Alzheimer’s disease via inhibiting gliosis. Exp. Neurol., 2022, 347, 113870.
[http://dx.doi.org/10.1016/j.expneurol.2021.113870] [PMID: 34563511]
[52]
Wang, J.; Liu, B.; Sun, F.; Xu, Y.; Luan, H.; Yang, M.; Wang, C.; Zhang, T.; Zhou, Z.; Yan, H. Histamine H3R antagonist counteracts the impaired hippocampal neurogenesis in Lipopolysaccharide-induced neuroinflammation. Int. Immunopharmacol., 2022, 110, 109045.
[http://dx.doi.org/10.1016/j.intimp.2022.109045] [PMID: 35978505]
[53]
Iida, T.; Yoshikawa, T.; Kárpáti, A.; Matsuzawa, T.; Kitano, H.; Mogi, A.; Harada, R.; Naganuma, F.; Nakamura, T.; Yanai, K. JNJ10181457, a histamine H3 receptor inverse agonist, regulates in vivo microglial functions and improves depression-like behaviours in mice. Biochem. Biophys. Res. Commun., 2017, 488(3), 534-540.
[http://dx.doi.org/10.1016/j.bbrc.2017.05.081] [PMID: 28526411]
[54]
Guilloux, J.P.; Samuels, B.A.; Mendez-David, I.; Hu, A.; Levinstein, M.; Faye, C.; Mekiri, M.; Mocaer, E.; Gardier, A.M.; Hen, R.; Sors, A.; David, D.J. S 38093, a histamine H3 antagonist/inverse agonist, promotes hippocampal neurogenesis and improves context discrimination task in aged mice. Sci. Rep., 2017, 7(1), 42946.
[http://dx.doi.org/10.1038/srep42946] [PMID: 28218311]
[55]
Mani, V.; Jaafar, S.M.; Azahan, N.S.M.; Ramasamy, K.; Lim, S.M.; Ming, L.C.; Majeed, A.B.A. Ciproxifan improves cholinergic transmission, attenuates neuroinflammation and oxidative stress but does not reduce amyloid level in transgenic mice. Life Sci., 2017, 180, 23-35.
[http://dx.doi.org/10.1016/j.lfs.2017.05.013] [PMID: 28501482]
[56]
Sheikh, S.; Safia; Haque, E.; Mir, S.S. Neurodegenerative diseases: Multifactorial conformational diseases and their therapeutic interventions. J. Neurodegener. Dis., 2013, 2013, 1-8.
[http://dx.doi.org/10.1155/2013/563481] [PMID: 26316993]
[57]
Vohora, D.; Bhowmik, M. Histamine H3 receptor antagonists/inverse agonists on cognitive and motor processes: Relevance to Alzheimer’s disease, ADHD, schizophrenia, and drug abuse. Front. Syst. Neurosci., 2012, 6, 72.
[http://dx.doi.org/10.3389/fnsys.2012.00072] [PMID: 23109919]
[58]
Cavalli, A.; Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M.; Melchiorre, C. Multi-target-directed ligands to combat neurodegenerative diseases. J. Med. Chem., 2008, 51(3), 347-372.
[http://dx.doi.org/10.1021/jm7009364] [PMID: 18181565]
[59]
Ramsay, R.R.; Popovic-Nikolic, M.R.; Nikolic, K.; Uliassi, E.; Bolognesi, M.L. A perspective on multi-target drug discovery and design for complex diseases. Clin. Transl. Med., 2018, 7(1), e3.
[http://dx.doi.org/10.1186/s40169-017-0181-2] [PMID: 29340951]
[60]
Matta, S.M.; Hill-Yardin, E.L.; Crack, P.J. The influence of neuroinflammation in Autism Spectrum Disorder. Brain Behav. Immun., 2019, 79, 75-90.
[http://dx.doi.org/10.1016/j.bbi.2019.04.037] [PMID: 31029798]
[61]
Baronio, D.; Gonchoroski, T.; Castro, K.; Zanatta, G.; Gottfried, C.; Riesgo, R. Histaminergic system in brain disorders: Lessons from the translational approach and future perspectives. Ann. Gen. Psychiatry, 2014, 13(1), 34.
[http://dx.doi.org/10.1186/s12991-014-0034-y] [PMID: 25426159]
[62]
Łażewska, D.; Jończyk, J.; Bajda, M.; Szałaj, N.; Więckowska, A.; Panek, D.; Moore, C.; Kuder, K.; Malawska, B.; Kieć-Kononowicz, K. Cholinesterase inhibitory activity of chlorophenoxy derivatives—Histamine H3 receptor ligands. Bioorg. Med. Chem. Lett., 2016, 26(16), 4140-4145.
[http://dx.doi.org/10.1016/j.bmcl.2016.04.054] [PMID: 27445168]
[63]
Eissa, N.; Azimullah, S.; Jayaprakash, P.; Jayaraj, R.L.; Reiner, D.; Ojha, S.K.; Beiram, R.; Stark, H.; Łażewska, D.; Kieć-Kononowicz, K.; Sadek, B. The dual-active histamine H3 receptor antagonist and acetylcholine esterase inhibitor E100 ameliorates stereotyped repetitive behavior and neuroinflammmation in sodium valproate induced autism in mice. Chem. Biol. Interact., 2019, 312, 108775.
[http://dx.doi.org/10.1016/j.cbi.2019.108775] [PMID: 31369746]
[64]
von Coburg, Y.; Kottke, T.; Weizel, L.; Ligneau, X.; Stark, H. Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics. Bioorg. Med. Chem. Lett., 2009, 19(2), 538-542.
[http://dx.doi.org/10.1016/j.bmcl.2008.09.012] [PMID: 19091563]
[65]
Maramai, S.; Gemma, S.; Brogi, S.; Campiani, G.; Butini, S.; Stark, H.; Brindisi, M. Dopamine D3 receptor antagonists as potential therapeutics for the treatment of neurological diseases. Front. Neurosci., 2016, 10, 451.
[http://dx.doi.org/10.3389/fnins.2016.00451] [PMID: 27761108]
[66]
Venkatachalam, K.; Eissa, N.; Awad, M.A.; Jayaprakash, P.; Zhong, S.; Stölting, F.; Stark, H.; Sadek, B. The histamine H3R and dopamine D2R/D3R antagonist ST-713 ameliorates autism- like behavioral features in BTBR T+tf/J mice by multiple actions. Biomed. Pharmacother., 2021, 138, 111517.
[http://dx.doi.org/10.1016/j.biopha.2021.111517] [PMID: 33773463]
[67]
Eissa, N.; Awad, M.A.; Thomas, S.D.; Venkatachalam, K.; Jayaprakash, P.; Zhong, S.; Stark, H.; Sadek, B. Simultaneous antagonism at H3R/D2R/D3R Reduces autism-like self-grooming and aggressive behaviors by mitigating mapk activation in mice. Int. J. Mol. Sci., 2022, 24(1), 526.
[http://dx.doi.org/10.3390/ijms24010526] [PMID: 36613969]
[68]
Bajda, M.; Łażewska, D.; Godyń, J.; Zaręba, P.; Kuder, K.; Hagenow, S.; Łątka, K.; Stawarska, E.; Stark, H.; Kieć-Kononowicz, K.; Malawska, B. Search for new multi-target compounds against Alzheimer’s disease among histamine H3 receptor ligands. Eur. J. Med. Chem., 2020, 185, 111785.
[http://dx.doi.org/10.1016/j.ejmech.2019.111785] [PMID: 31669851]
[69]
Honkisz-Orzechowska, E.; Popiołek-Barczyk, K.; Linart, Z.; Filipek-Gorzała, J.; Rudnicka, A.; Siwek, A.; Werner, T.; Stark, H.; Chwastek, J.; Starowicz, K.; Kieć-Kononowicz, K.; Łażewska, D. Anti-inflammatory effects of new human histamine H3 receptor ligands with flavonoid structure on BV-2 neuroinflammation. Inflamm. Res., 2023, 72(2), 181-194.
[http://dx.doi.org/10.1007/s00011-022-01658-z] [PMID: 36370200]
[70]
Devi, S.; Kumar, V.; Singh, S.K.; Dubey, A.K.; Kim, J.J. Flavonoids: Potential candidates for the treatment of neurodegenerative disorders. Biomedicines, 2021, 9(2), 99.
[http://dx.doi.org/10.3390/biomedicines9020099] [PMID: 33498503]
[71]
Adelusi, T.I.; Akinbolaji, G.R.; Yin, X.; Ayinde, K.S.; Olaoba, O.T. Neurotrophic, anti-neuroinflammatory, and redox balance mechanisms of chalcones. Eur. J. Pharmacol., 2021, 891, 173695.
[http://dx.doi.org/10.1016/j.ejphar.2020.173695] [PMID: 33121951]
[72]
Li, S.; Yang, J. Pitolisant for treating patients with narcolepsy. Expert Rev. Clin. Pharmacol., 2020, 13(2), 79-84.
[http://dx.doi.org/10.1080/17512433.2020.1714435] [PMID: 31937172]
[73]
Keam, S.J. Pitolisant: Pediatric first approval. Paediatr. Drugs, 2023, 25(4), 483-488.
[http://dx.doi.org/10.1007/s40272-023-00575-w] [PMID: 37233887]
[74]
Nirogi, R.; Mudigonda, K.; Bhyrapuneni, G.; Muddana, N.R.; Shinde, A.; Goyal, V.K.; Pandey, S.K.; Mohammed, A.R.; Ravula, J.; Jetta, S.; Palacharla, V.R.C. Safety, tolerability, and pharmacokinetics of SUVN-G3031, a novel histamine-3 receptor inverse agonist for the treatment of narcolepsy, in healthy human subjects following single and multiple oral doses. Clin. Drug Investig., 2020, 40(7), 603-615.
[http://dx.doi.org/10.1007/s40261-020-00920-8] [PMID: 32399853]
[75]
Nathan, P.J.; Boardley, R.; Scott, N.; Berges, A.; Maruff, P.; Sivananthan, T.; Upton, N.; Lowy, M.T.; Nestor, P.J.; Lai, R. The safety, tolerability, pharmacokinetics and cognitive effects of GSK239512, a selective histamine H₃ receptor antagonist in patients with mild to moderate Alzheimer’s disease: A preliminary investigation. Curr. Alzheimer Res., 2013, 10(3), 240-251.
[http://dx.doi.org/10.2174/1567205011310030003] [PMID: 23521503]
[76]
Yoshikawa, T.; Nakamura, T.; Yanai, K. Histamine N-Methyltransferase in the Brain. Int. J. Mol. Sci., 2019, 20(3), 737.
[http://dx.doi.org/10.3390/ijms20030737] [PMID: 30744146]

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