Generic placeholder image

Current Topics in Medicinal Chemistry

Editor-in-Chief

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

Review Article

Multilevel Pharmacological Effects of Antipsychotics in Potential Glioblastoma Treatment

Author(s): Wireko Andrew Awuah*, Jacob Kalmanovich, Aashna Mehta, Helen Huang, Toufik Abdul-Rahman, Jyi Cheng Ng, Rohan Yarlagadda, Karl Kamanousa, Mrinmoy Kundu, Esther Patience Nansubuga, Mohammad Mehedi Hasan, Mykola Lyndin, Arda Isik, Vladyslav Sikora and Athanasios Alexiou*

Volume 23, Issue 5, 2023

Published on: 20 January, 2023

Page: [389 - 402] Pages: 14

DOI: 10.2174/1568026623666230102095836

Price: $65

Abstract

Glioblastoma Multiforme (GBM) is a debilitating type of brain cancer with a high mortality rate. Despite current treatment options such as surgery, radiotherapy, and the use of temozolomide and bevacizumab, it is considered incurable. Various methods, such as drug repositioning, have been used to increase the number of available treatments. Drug repositioning is the use of FDA-approved drugs to treat other diseases. This is possible because the drugs used for this purpose have polypharmacological effects. This means that these medications can bind to multiple targets, resulting in multiple mechanisms of action. Antipsychotics are one type of drug used to treat GBM. Antipsychotics are a broad class of drugs that can be further subdivided into typical and atypical classes. Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide. This class of antipsychotics was developed early on and primarily works on dopamine D2 receptors, though it can also work on others. Olanzapine and Quetiapine are examples of atypical antipsychotics, a category that was created later. These medications have a high affinity for serotonin receptors such as 5- HT2, but they can also act on dopamine and H1 receptors. Antipsychotic medications, in the case of GBM, also have other effects that can affect multiple pathways due to their polypharmacological effects. These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsychotics in the treatment of GBM, and an outlook for the field's future progression.

Graphical Abstract

[1]
Holland, E.C. Glioblastoma multiforme: The terminator. Proc. Natl. Acad. Sci. USA, 2000, 97(12), 6242-6244.
[http://dx.doi.org/10.1073/pnas.97.12.6242] [PMID: 10841526]
[2]
Maher, E.A.; Furnari, F.B.; Bachoo, R.M.; Rowitch, D.H.; Louis, D.N.; Cavenee, W.K.; DePinho, R.A. Malignant glioma: Genetics and biology of a grave matter. Genes Dev., 2001, 15(11), 1311-1333.
[http://dx.doi.org/10.1101/gad.891601] [PMID: 11390353]
[3]
Schwartzbaum, J.A.; Fisher, J.L.; Aldape, K.D.; Wrensch, M. Epidemiology and molecular pathology of glioma. Nat. Clin. Pract. Neurol., 2006, 2(9), 494-516.
[http://dx.doi.org/10.1038/ncpneuro0289]
[4]
Agnihotri, S.; Burrell, K.E.; Wolf, A.; Jalali, S.; Hawkins, C.; Rutka, J.T.; Zadeh, G. Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies. Arch. Immunol. Ther. Exp. (Warsz.), 2013, 61(1), 25-41.
[http://dx.doi.org/10.1007/s00005-012-0203-0] [PMID: 23224339]
[5]
Ohgaki, H.; Kleihues, P. Epidemiology and etiology of gliomas. Acta Neuropathol., 2005, 109(1), 93-108.
[http://dx.doi.org/10.1007/s00401-005-0991-y] [PMID: 15685439]
[6]
Tran, B.; Rosenthal, M.A. Survival comparison between glioblastoma multiforme and other incurable cancers. J. Clin. Neurosci., 2010, 17(4), 417-421.
[http://dx.doi.org/10.1016/j.jocn.2009.09.004] [PMID: 20167494]
[7]
Ohka, F.; Natsume, A.; Wakabayashi, T. Current trends in targeted therapies for glioblastoma multiforme. Neurol. Res. Int., 2012, 2012, 878425.
[http://dx.doi.org/10.1155/2012/878425] [PMID: 22530127]
[8]
Roh, T.H.; Kang, S.G.; Moon, J.H.; Sung, K.S.; Park, H.H.; Kim, S.H.; Kim, E.H.; Hong, C.K.; Suh, C.O.; Chang, J.H. Survival benefit of lobectomy over gross-total resection without lobectomy in cases of glioblastoma in the noneloquent area: A retrospective study. J. Neurosurg., 2020, 132(3), 895-901.
[http://dx.doi.org/10.3171/2018.12.JNS182558] [PMID: 30835701]
[9]
Huang, B.; Li, X.; Li, Y.; Zhang, J.; Zong, Z.; Zhang, H. Current immunotherapies for glioblastoma multiforme. Front. Immunol., 2021, 11, 603911.
[http://dx.doi.org/10.3389/fimmu.2020.603911] [PMID: 33767690]
[10]
Wrensch, M.; Minn, Y.; Chew, T.; Bondy, M.; Berger, M.S. Epidemiology of primary brain tumors: Current concepts and review of the literature. Neuro-oncol., 2002, 4(4), 278-299.
[http://dx.doi.org/10.1093/neuonc/4.4.278] [PMID: 12356358]
[11]
Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.; Burger, P.C.; Jouvet, A.; Scheithauer, B.W.; Kleihues, P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol., 2007, 114(2), 97-109.
[http://dx.doi.org/10.1007/s00401-007-0243-4] [PMID: 17618441]
[12]
Wen, P.Y.; Kesari, S. Malignant gliomas in adults. N. Engl. J. Med., 2008, 359(5), 492-507.
[http://dx.doi.org/10.1056/NEJMra0708126] [PMID: 18669428]
[13]
Davis, M.E. Epidemiology and overview of gliomas. Semin. Oncol. Nurs., 2018, 34(5), 420-429.
[http://dx.doi.org/10.1016/j.soncn.2018.10.001] [PMID: 30392758]
[14]
Sulman, E.P.; Ismaila, N.; Armstrong, T.S.; Tsien, C.; Batchelor, T.T.; Cloughesy, T.; Galanis, E.; Gilbert, M.; Gondi, V.; Lovely, M.; Mehta, M.; Mumber, M.P.; Sloan, A.; Chang, S.M. Radiation therapy for glioblastoma: American society of clinical oncology clinical practice guideline endorsement of the american society for radiation oncology guideline. J. Clin. Oncol., 2017, 35(3), 361-369.
[http://dx.doi.org/10.1200/JCO.2016.70.7562] [PMID: 27893327]
[15]
Nabors, L.B.; Portnow, J.; Ahluwalia, M.; Baehring, J.; Brem, H.; Brem, S.; Butowski, N.; Campian, J.L.; Clark, S.W.; Fabiano, A.J.; Forsyth, P.; Hattangadi-Gluth, J.; Holdhoff, M.; Horbinski, C.; Junck, L.; Kaley, T.; Kumthekar, P.; Loeffler, J.S.; Mrugala, M.M.; Nagpal, S.; Pandey, M.; Parney, I.; Peters, K.; Puduvalli, V.K.; Robins, I.; Rockhill, J.; Rusthoven, C.; Shonka, N.; Shrieve, D.C.; Swinnen, L.J.; Weiss, S.; Wen, P.Y.; Willmarth, N.E.; Bergman, M.A.; Darlow, S.D. Central nervous system cancers, version 3.2020, nccn clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw., 2020, 18(11), 1537-1570.
[http://dx.doi.org/10.6004/jnccn.2020.0052] [PMID: 33152694]
[16]
Jiang, T.; Nam, D.H.; Ram, Z.; Poon, W.; Wang, J.; Boldbaatar, D.; Mao, Y.; Ma, W.; Mao, Q.; You, Y.; Jiang, C.; Yang, X.; Kang, C.; Qiu, X.; Li, W.; Li, S.; Chen, L.; Li, X.; Liu, Z.; Wang, W.; Bai, H.; Yao, Y.; Li, S.; Wu, A.; Sai, K.; Li, G.; Yao, K.; Wei, X.; Liu, X.; Zhang, Z.; Dai, Y.; Lv, S.; Wang, L.; Lin, Z.; Dong, J.; Xu, G.; Ma, X.; Zhang, W.; Zhang, C.; Chen, B.; You, G.; Wang, Y.; Wang, Y.; Bao, Z.; Yang, P.; Fan, X.; Liu, X.; Zhao, Z.; Wang, Z.; Li, Y.; Wang, Z.; Li, G.; Fang, S.; Li, L.; Liu, Y.; Liu, S.; Shan, X.; Liu, Y.; Chai, R.; Hu, H.; Chen, J.; Yan, W.; Cai, J.; Wang, H.; Chen, L.; Yang, Y.; Wang, Y.; Han, L.; Wang, Q. Clinical practice guidelines for the management of adult diffuse gliomas. Cancer Lett., 2021, 499, 60-72.
[http://dx.doi.org/10.1016/j.canlet.2020.10.050] [PMID: 33166616]
[17]
Weller, M.; van den Bent, M.; Preusser, M.; Le Rhun, E.; Tonn, J.C.; Minniti, G.; Bendszus, M.; Balana, C.; Chinot, O.; Dirven, L.; French, P.; Hegi, M.E.; Jakola, A.S.; Platten, M.; Roth, P.; Rudà, R.; Short, S.; Smits, M.; Taphoorn, M.J.B.; von Deimling, A.; Westphal, M.; Soffietti, R.; Reifenberger, G.; Wick, W. Author correction: EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat. Rev. Clin. Oncol., 2022, 19(5), 357-358.
[http://dx.doi.org/10.1038/s41571-022-00623-3] [PMID: 35322237]
[18]
Stummer, W.; Pichlmeier, U.; Meinel, T.; Wiestler, O.D.; Zanella, F.; Reulen, H.J. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A randomised controlled multicentre phase III trial. Lancet Oncol., 2006, 7(5), 392-401.
[http://dx.doi.org/10.1016/S1470-2045(06)70665-9] [PMID: 16648043]
[19]
Farrell, C.; Shi, W.; Bodman, A.; Olson, J.J. Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma. J. Neurooncol., 2020, 150(2), 269-359.
[http://dx.doi.org/10.1007/s11060-020-03607-4] [PMID: 33215345]
[20]
Stupp, R.; Hegi, M.E.; Mason, W.P.; van den Bent, M.J.; Taphoorn, M.J.B.; Janzer, R.C.; Ludwin, S.K.; Allgeier, A.; Fisher, B.; Belanger, K.; Hau, P.; Brandes, A.A.; Gijtenbeek, J.; Marosi, C.; Vecht, C.J.; Mokhtari, K.; Wesseling, P.; Villa, S.; Eisenhauer, E.; Gorlia, T.; Weller, M.; Lacombe, D.; Cairncross, J.G.; Mirimanoff, R.O. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol., 2009, 10(5), 459-466.
[http://dx.doi.org/10.1016/S1470-2045(09)70025-7] [PMID: 19269895]
[21]
Malmström, A.; Grønberg, B.H.; Marosi, C.; Stupp, R.; Frappaz, D.; Schultz, H.; Abacioglu, U.; Tavelin, B.; Lhermitte, B.; Hegi, M.E.; Rosell, J.; Henriksson, R. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: The Nordic randomised, phase 3 trial. Lancet Oncol., 2012, 13(9), 916-926.
[http://dx.doi.org/10.1016/S1470-2045(12)70265-6] [PMID: 22877848]
[22]
Eigenbrod, S.; Trabold, R.; Brucker, D.; Erös, C.; Egensperger, R.; La Fougere, C.; Göbel, W.; Rühm, A.; Kretzschmar, H.A.; Tonn, J.C.; Herms, J.; Giese, A.; Kreth, F.W. Molecular stereotactic biopsy technique improves diagnostic accuracy and enables personalized treatment strategies in glioma patients. Acta Neurochir., 2014, 156(8), 1427-1440.
[http://dx.doi.org/10.1007/s00701-014-2073-1] [PMID: 24792966]
[23]
Mohile, N.A.; Messersmith, H.; Gatson, N.T.; Hottinger, A.F.; Lassman, A.; Morton, J.; Ney, D.; Nghiemphu, P.L.; Olar, A.; Olson, J.; Perry, J.; Portnow, J.; Schiff, D.; Shannon, A.; Shih, H.A.; Strowd, R.; van den Bent, M.; Ziu, M.; Blakeley, J. Therapy for diffuse astrocytic and oligodendroglial tumors in adults: ASCO-SNO guideline. J. Clin. Oncol., 2022, 40(4), 403-426.
[http://dx.doi.org/10.1200/JCO.21.02036] [PMID: 34898238]
[24]
Perry, J.R.; Laperriere, N.; O’Callaghan, C.J.; Brandes, A.A.; Menten, J.; Phillips, C.; Fay, M.; Nishikawa, R.; Cairncross, J.G.; Roa, W.; Osoba, D.; Rossiter, J.P.; Sahgal, A.; Hirte, H.; Laigle-Donadey, F.; Franceschi, E.; Chinot, O.; Golfinopoulos, V.; Fariselli, L.; Wick, A.; Feuvret, L.; Back, M.; Tills, M.; Winch, C.; Baumert, B.G.; Wick, W.; Ding, K.; Mason, W.P. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N. Engl. J. Med., 2017, 376(11), 1027-1037.
[http://dx.doi.org/10.1056/NEJMoa1611977] [PMID: 28296618]
[25]
Ostrom, Q.T.; Cioffi, G.; Gittleman, H.; Patil, N.; Waite, K.; Kruchko, C.; Barnholtz-Sloan, J.S. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the united states in 2012–2016. Neuro-oncol., 2019, 21(S5), v1-v100.
[http://dx.doi.org/10.1093/neuonc/noz150] [PMID: 31675094]
[26]
Motl, S.; Zhuang, Y.; Waters, C.M.; Stewart, C.F. Pharmacokinetic considerations in the treatment of CNS tumours. Clin. Pharmacokinet., 2006, 45(9), 871-903.
[http://dx.doi.org/10.2165/00003088-200645090-00002] [PMID: 16928151]
[27]
Muldoon, L.L.; Soussain, C.; Jahnke, K.; Johanson, C.; Siegal, T.; Smith, Q.R.; Hall, W.A.; Hynynen, K.; Senter, P.D.; Peereboom, D.M.; Neuwelt, E.A. Chemotherapy delivery issues in central nervous system malignancy: A reality check. J. Clin. Oncol., 2007, 25(16), 2295-2305.
[http://dx.doi.org/10.1200/JCO.2006.09.9861] [PMID: 17538176]
[28]
Cecchelli, R.; Berezowski, V.; Lundquist, S.; Culot, M.; Renftel, M.; Dehouck, M.P.; Fenart, L. Modelling of the blood–brain barrier in drug discovery and development. Nat. Rev. Drug Discov., 2007, 6(8), 650-661.
[http://dx.doi.org/10.1038/nrd2368] [PMID: 17667956]
[29]
Urquhart, B.L.; Kim, R.B. Blood−brain barrier transporters and response to CNS-active drugs. Eur. J. Clin. Pharmacol., 2009, 65(11), 1063-1070.
[http://dx.doi.org/10.1007/s00228-009-0714-8] [PMID: 19727692]
[30]
Vescovi, A.L.; Galli, R.; Reynolds, B.A. Brain tumour stem cells. Nat. Rev. Cancer, 2006, 6(6), 425-436.
[http://dx.doi.org/10.1038/nrc1889] [PMID: 16723989]
[31]
Clarke, M.F.; Dick, J.E.; Dirks, P.B.; Eaves, C.J.; Jamieson, C.H.M.; Jones, D.L.; Visvader, J.; Weissman, I.L.; Wahl, G.M. Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res., 2006, 66(19), 9339-9344.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3126] [PMID: 16990346]
[32]
Chen, J.; McKay, R.M.; Parada, L.F. Malignant glioma: Lessons from genomics, mouse models, and stem cells. Cell, 2012, 149(1), 36-47.
[http://dx.doi.org/10.1016/j.cell.2012.03.009] [PMID: 22464322]
[33]
Ashburn, T.T.; Thor, K.B. Drug repositioning: Identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov., 2004, 3(8), 673-683.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[34]
Low, Z.Y.; Farouk, I.A.; Lal, S.K. Drug repositioning: New approaches and future prospects for life-debilitating diseases and the covid-19 pandemic outbreak. Viruses, 2020, 12(9), 1058.
[http://dx.doi.org/10.3390/v12091058] [PMID: 32972027]
[35]
Tan, S.K.; Jermakowicz, A.; Mookhtiar, A.K.; Nemeroff, C.B.; Schürer, S.C.; Ayad, N.G. Drug repositioning in glioblastoma: A pathway perspective. Front. Pharmacol., 2018, 9, 218.
[http://dx.doi.org/10.3389/fphar.2018.00218] [PMID: 29615902]
[36]
Lee, J.K.; Nam, D.H.; Lee, J. Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges. Oncol. Lett., 2016, 11(2), 1281-1286.
[http://dx.doi.org/10.3892/ol.2016.4074] [PMID: 26893731]
[37]
Barak, Y.; Achiron, A.; Mandel, M.; Mirecki, I.; Aizenberg, D. Reduced cancer incidence among patients with schizophrenia. Cancer, 2005, 104(12), 2817-2821.
[http://dx.doi.org/10.1002/cncr.21574] [PMID: 16288491]
[38]
Chou, F.H.C.; Tsai, K.Y.; Su, C.Y.; Lee, C.C. The incidence and relative risk factors for developing cancer among patients with schizophrenia: A nine-year follow-up study. Schizophr. Res., 2011, 129(2-3), 97-103.
[http://dx.doi.org/10.1016/j.schres.2011.02.018] [PMID: 21458957]
[39]
Pettersson, D.; Gissler, M.; Hällgren, J.; Ösby, U.; Westman, J.; Bobo, W.V. The overall and sex- and age-group specific incidence rates of cancer in people with schizophrenia: A population-based cohort study. Epidemiol. Psychiatr. Sci., 2020, 29, e132.
[http://dx.doi.org/10.1017/S204579602000044X] [PMID: 32460950]
[40]
Kondej, M. Stępnicki, P.; Kaczor, A.A. Multi-target approach for drug discovery against schizophrenia. Int. J. Mol. Sci., 2018, 19(10), 3105.
[http://dx.doi.org/10.3390/ijms19103105] [PMID: 30309037]
[41]
Shin, S.Y.; Lee, K.S.; Choi, Y.K.; Lim, H.J.; Lee, H.G.; Lim, Y.; Lee, Y.H. The antipsychotic agent chlorpromazine induces autophagic cell death by inhibiting the Akt/mTOR pathway in human U-87MG glioma cells. Carcinogenesis, 2013, 34(9), 2080-2089.
[http://dx.doi.org/10.1093/carcin/bgt169] [PMID: 23689352]
[42]
Kaushik, I.; Ramachandran, S.; Prasad, S.; Srivastava, S.K. Drug rechanneling: A novel paradigm for cancer treatment. Semin. Cancer Biol., 2021, 68, 279-290.
[http://dx.doi.org/10.1016/j.semcancer.2020.03.011] [PMID: 32437876]
[43]
Paul, S.M.; Mytelka, D.S.; Dunwiddie, C.T.; Persinger, C.C.; Munos, B.H.; Lindborg, S.R.; Schacht, A.L. How to improve R & D productivity: the pharmaceutical industry’s grand challenge. Nat. Rev. Drug Discov., 2010, 9(3), 203-214.
[44]
Hay, M.; Thomas, D.W.; Craighead, J.L.; Economides, C.; Rosenthal, J. Clinical development success rates for investigational drugs. Nat. Biotechnol., 2014, 32(1), 40-51.
[http://dx.doi.org/10.1038/nbt.2786] [PMID: 24406927]
[45]
Li, H.; Li, J.; Yu, X.; Zheng, H.; Sun, X.; Lu, Y.; Zhang, Y.; Li, C.; Bi, X. The incidence rate of cancer in patients with schizophrenia: A meta-analysis of cohort studies. Schizophr. Res., 2018, 195, 519-528.
[http://dx.doi.org/10.1016/j.schres.2017.08.065] [PMID: 28943096]
[46]
Vlachos, N.; Lampros, M.; Voulgaris, S.; Alexiou, G.A. Repurposing antipsychotics for cancer treatment. Biomedicines, 2021, 9(12), 1785.
[http://dx.doi.org/10.3390/biomedicines9121785] [PMID: 34944601]
[47]
Mortensen, P.B. Neuroleptic medication and reduced risk of prostate cancer in schizophrenic patients. Acta Psychiatr. Scand., 1992, 85(5), 390-393.
[http://dx.doi.org/10.1111/j.1600-0447.1992.tb10325.x] [PMID: 1351334]
[48]
Saudemont, G.; Prod’Homme, C.; Da Silva, A.; Villet, S.; Reich, M.; Penel, N.; Gamblin, V. The use of olanzapine as an antiemetic in palliative medicine: a systematic review of the literature. BMC Palliat. Care, 2020, 19(1), 56.
[http://dx.doi.org/10.1186/s12904-020-00559-4] [PMID: 32321488]
[49]
Dazzan, P.; Morgan, K.D.; Orr, K.; Hutchinson, G.; Chitnis, X.; Suckling, J.; Fearon, P.; McGuire, P.K.; Mallett, R.M.; Jones, P.B.; Leff, J.; Murray, R.M. Different effects of typical and atypical antipsychotics on grey matter in first episode psychosis: the AESOP study. Neuropsychopharmacology, 2005, 30(4), 765-774.
[http://dx.doi.org/10.1038/sj.npp.1300603] [PMID: 15702141]
[50]
You, F.; Zhang, C.; Liu, X.; Ji, D.; Zhang, T.; Yu, R.; Gao, S. Drug repositioning: Using psychotropic drugs for the treatment of glioma. Cancer Lett., 2022, 527, 140-149.
[http://dx.doi.org/10.1016/j.canlet.2021.12.014] [PMID: 34923043]
[51]
Zhuo, C.; Xun, Z.; Hou, W.; Ji, F.; Lin, X.; Tian, H.; Zheng, W.; Chen, M.; Liu, C.; Wang, W.; Chen, C. Surprising anticancer activities of psychiatric medications: old drugs offer new hope for patients with brain cancer. Front. Pharmacol., 2019, 10, 1262.
[http://dx.doi.org/10.3389/fphar.2019.01262] [PMID: 31695618]
[52]
Li, J.; Zhu, S.; Kozono, D.; Ng, K.; Futalan, D.; Shen, Y.; Akers, J.C.; Steed, T.; Kushwaha, D.; Schlabach, M.; Carter, B.S.; Kwon, C.H.; Furnari, F.; Cavenee, W.; Elledge, S.; Chen, C.C. Genome-wide shRNA screen revealed integrated mitogenic signaling between dopamine receptor D2 (DRD2) and epidermal growth factor receptor (EGFR) in glioblastoma. Oncotarget, 2014, 5(4), 882-893.
[http://dx.doi.org/10.18632/oncotarget.1801] [PMID: 24658464]
[53]
Zhu, Y.; Zhao, Y.F.; Liu, R.S.; Xiong, Y.J.; Shen, X.; Wang, Y.; Liang, Z.Q. Olanzapine induced autophagy through suppression of NF‐κB activation in human glioma cells. CNS Neurosci. Ther., 2019, 25(9), 911-921.
[http://dx.doi.org/10.1111/cns.13127] [PMID: 30955240]
[54]
Kirk, S.L.; Glazebrook, J.; Grayson, B.; Neill, J.C.; Reynolds, G.P. Olanzapine-induced weight gain in the rat: role of 5-HT2C and histamine H1 receptors. Psychopharmacology, 2009, 207(1), 119-125.
[http://dx.doi.org/10.1007/s00213-009-1639-8] [PMID: 19688201]
[55]
Karpel-Massler, G.; Kast, R.E.; Westhoff, M.A.; Dwucet, A.; Welscher, N.; Nonnenmacher, L.; Hlavac, M.; Siegelin, M.D.; Wirtz, C.R.; Debatin, K.M.; Halatsch, M.E. Olanzapine inhibits proliferation, migration and anchorage-independent growth in human glioblastoma cell lines and enhances temozolomide’s antiproliferative effect. J. Neurooncol., 2015, 122(1), 21-33.
[http://dx.doi.org/10.1007/s11060-014-1688-7] [PMID: 25524815]
[56]
Shin, S.Y.; Kim, C.G.; Kim, S.H.; Kim, Y.S.; Lim, Y.; Lee, Y.H. Chlorpromazine activates p21 Waf1/Cip1 gene transcription via early growth response-1 (Egr-1) in C6 glioma cells. Exp. Mol. Med., 2010, 42(5), 395-405.
[http://dx.doi.org/10.3858/emm.2010.42.5.041] [PMID: 20368687]
[57]
Matteoni, S.; Matarrese, P.; Ascione, B.; Ricci-Vitiani, L.; Pallini, R.; Villani, V.; Pace, A.; Paggi, M.G.; Abbruzzese, C. Chlorpromazine induces cytotoxic autophagy in glioblastoma cells via endoplasmic reticulum stress and unfolded protein response. J. Exp. Clin. Cancer Res., 2021, 40(1), 347.
[http://dx.doi.org/10.1186/s13046-021-02144-w] [PMID: 34740374]
[58]
Oliva, C.R.; Zhang, W.; Langford, C.; Suto, M.J.; Griguer, C.E. Repositioning chlorpromazine for treating chemoresistant glioma through the inhibition of cytochrome c oxidase bearing the COX4-1 regulatory subunit. Oncotarget, 2017, 8(23), 37568-37583.
[http://dx.doi.org/10.18632/oncotarget.17247] [PMID: 28455961]
[59]
Matteoni, S.; Matarrese, P.; Ascione, B.; Buccarelli, M.; Ricci-Vitiani, L.; Pallini, R.; Villani, V.; Pace, A.; Paggi, M.G.; Abbruzzese, C. Anticancer properties of the antipsychotic drug chlorpromazine and its synergism with temozolomide in restraining human glioblastoma proliferation in vitro. Front. Oncol., 2021, 11, 635472.
[http://dx.doi.org/10.3389/fonc.2021.635472] [PMID: 33718225]
[60]
Wang, Y.; Huang, N.; Li, H.; Liu, S.; Chen, X.; Yu, S.; Wu, N.; Bian, X.W.; Shen, H.Y.; Li, C.; Xiao, L. Promoting oligodendroglial-oriented differentiation of glioma stem cell: a repurposing of quetiapine for the treatment of malignant glioma. Oncotarget, 2017, 8(23), 37511-37524.
[http://dx.doi.org/10.18632/oncotarget.16400] [PMID: 28415586]
[61]
Pai, S.G.; Carneiro, B.A.; Mota, J.M.; Costa, R.; Leite, C.A.; Barroso-Sousa, R.; Kaplan, J.B.; Chae, Y.K.; Giles, F.J. Wnt/beta-catenin pathway: Modulating anticancer immune response. J. Hematol. Oncol., 2017, 10(1), 101.
[http://dx.doi.org/10.1186/s13045-017-0471-6] [PMID: 28476164]
[62]
Liu, P.; Cheng, H.; Roberts, T.M.; Zhao, J.J. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat. Rev. Drug Discov., 2009, 8(8), 627-644.
[http://dx.doi.org/10.1038/nrd2926] [PMID: 19644473]
[63]
Karbownik, M.S.; Szemraj, J.S. Wieteska, Ł.; Antczak, A.; Górski, P.; Kowalczyk, E.; Pietras, T. Antipsychotic drugs differentially affect mRNA expression of genes encoding the neuregulin 1-downstream ErbB4-PI3K pathway. Pharmacology, 2016, 98, 4-12.
[64]
Marques, L.O.; Lima, M.S.; Soares, B.G.O. Trifluoperazine for schizophrenia. Cochrane Database Syst. Rev., 2004, 2004(1), CD003545.
[PMID: 14974020]
[65]
Yang, S-Y.; Kao, Yang Y-H.; Chong, M-Y.; Yang, Y-H.; Chang, W-H.; Lai, C-S. Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study. Clin. Pharmacol. Ther., 2007, 81(4), 586-594.
[http://dx.doi.org/10.1038/sj.clpt.6100069] [PMID: 17235331]
[66]
Timmins, J.M.; Ozcan, L.; Seimon, T.A.; Li, G.; Malagelada, C.; Backs, J. Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. American Society for Clinical Investigation, 2009. Available from: https://www.jci.org/articles/view/38857/citations [cited 2022 Jun 9].
[67]
Fancy, R.M.; Kim, H.; Napier, T.; Buchsbaum, D.J.; Zinn, K.R.; Song, Y. Calmodulin antagonist enhances DR5‐mediated apoptotic signaling in TRA‐8 resistant triple negative breast cancer cells. J. Cell. Biochem., 2018, 119(7), 6216-6230.
[http://dx.doi.org/10.1002/jcb.26848] [PMID: 29663486]
[68]
Brosius, S.N.; Turk, A.N.; Byer, S.J.; Longo, J.F.; Kappes, J.C.; Roth, K.A.; Carroll, S.L. Combinatorial therapy with tamoxifen and trifluoperazine effectively inhibits malignant peripheral nerve sheath tumor growth by targeting complementary signaling cascades. J. Neuropathol. Exp. Neurol., 2014, 73(11), 1078-1090.
[http://dx.doi.org/10.1097/NEN.0000000000000126] [PMID: 25289889]
[69]
Villalobo, A.; Berchtold, M.W. The role of calmodulin in tumor cell migration, invasiveness, and metastasis. Int. J. Mol. Sci., 2020, 21(3), 765.
[http://dx.doi.org/10.3390/ijms21030765] [PMID: 31991573]
[70]
Li, T.; Yi, L.; Hai, L.; Ma, H.; Tao, Z.; Zhang, C.; Abeysekera, I.R.; Zhao, K.; Yang, Y.; Wang, W.; Liu, B.; Yu, S.; Tong, L.; Liu, P.; Zhu, M.; Ren, B.; Lin, Y.; Zhang, K.; Cheng, C.; Huang, Y.; Yang, X. The interactome and spatial redistribution feature of Ca2+ receptor protein calmodulin reveals a novel role in invadopodia-mediated invasion. Cell Death Dis., 2018, 9(3), 292.
[http://dx.doi.org/10.1038/s41419-017-0253-7] [PMID: 29463791]
[71]
Kang, S.; Lee, J.M.; Jeon, B.; Elkamhawy, A.; Paik, S.; Hong, J.; Oh, S.J.; Paek, S.H.; Lee, C.J.; Hassan, A.H.E.; Kang, S.S.; Roh, E.J. Repositioning of the antipsychotic trifluoperazine: Synthesis, biological evaluation and in silico study of trifluoperazine analogs as anti-glioblastoma agents. Eur. J. Med. Chem., 2018, 151, 186-198.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.055] [PMID: 29614416]
[72]
Haynes, D.H.; Werber, M.M. Inhibition of the Ca2+-Mg2+ ATPase of sarcoplasmic reticulum by Co-(phen)-ATP. Membr. Biochem., 1982, 4(4), 247-257.
[http://dx.doi.org/10.3109/09687688209065434] [PMID: 6129563]
[73]
Dolma, S.; Selvadurai, H.J.; Lan, X.; Lee, L.; Kushida, M.; Voisin, V.; Whetstone, H.; So, M.; Aviv, T.; Park, N.; Zhu, X.; Xu, C.; Head, R.; Rowland, K.J.; Bernstein, M.; Clarke, I.D.; Bader, G.; Harrington, L.; Brumell, J.H.; Tyers, M.; Dirks, P.B. Inhibition of dopamine receptor d4 impedes autophagic flux, proliferation, and survival of glioblastoma stem cells. Cancer Cell, 2016, 29(6), 859-873.
[http://dx.doi.org/10.1016/j.ccell.2016.05.002] [PMID: 27300435]
[74]
Kruttika, B.; Mohammad, S.; Erina, V.; Frank, P. The dopamine receptor antagonist trifluoperazine prevents phenotype conversion and improves survival in mouse models of glioblastoma. PNAS, 2020, 117(20), 11085-11096.
[http://dx.doi.org/10.1073/pnas.1920154117]
[75]
Botrugno, O.A.; Robert, T.; Vanoli, F.; Foiani, M.; Minucci, S. Molecular pathways: Old drugs define new pathways: non-histone acetylation at the crossroads of the DNA damage response and autophagy. Clin. Cancer Res., 2012, 18(9), 2436-2442.
[http://dx.doi.org/10.1158/1078-0432.CCR-11-0767] [PMID: 22512979]
[76]
Gangopadhyay, S.; Karmakar, P.; Dasgupta, U.; Chakraborty, A. Trifluoperazine stimulates ionizing radiation induced cell killing through inhibition of DNA repair. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2007, 633(2), 117-125.
[http://dx.doi.org/10.1016/j.mrgentox.2007.05.011] [PMID: 17627868]
[77]
Davis, C. Pimozide. In: xPharm: The Comprehensive Pharmacology Reference; Enna, S.J.; Bylund, D.B., Eds.; Elsevier: New York, 2007; pp. 1-5.
[78]
Gopalakrishnan, M.; Gobburu, J.V.S. Regulatory perspectives on the use of biomarkers and personalized medicine in cns drug development: The FDA viewpoint. In: Handbook of Behavioral Neuroscience; Nomikos, G.G.; Feltner, DE, Eds.; Elsevier, 2019; 29, pp. 247-58. Available from: https://www.sciencedirect.com/science/article/pii/B9780128031612000187
[79]
Pinder, R.M.; Brogden, R.N.; Sawyer, P.R.; Speight, T.M.; Spencer, R.; Avery, G.S. Pimozide: A review of its pharmacological properties and therapeutic uses in psychiatry. Drugs, 1976, 12(1), 1-40.
[http://dx.doi.org/10.2165/00003495-197612010-00001] [PMID: 824116]
[80]
Silva, M.R.; Bernardi, M.M.; Cruz-Casallas, P.E.; Felicio, L.F. Pimozide injections into the Nucleus accumbens disrupt maternal behaviour in lactating rats. Pharmacology & Toxicology, 2003, 93(1), 42-47.
[http://dx.doi.org/10.1034/j.1600-0773.2003.930106.x]
[81]
Amato, D.; Kruyer, A.; Samaha, A.N.; Heinz, A. Hypofunctional dopamine uptake and antipsychotic treatment-resistant schizophrenia. Front. Psychiatry, 2019, 10, 314.
[http://dx.doi.org/10.3389/fpsyt.2019.00314] [PMID: 31214054]
[82]
Svensson, T.H. α-Adrenoceptor modulation hypothesis of antipsychotic atypicality. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2003, 27(7), 1145-1158.
[http://dx.doi.org/10.1016/j.pnpbp.2003.09.009] [PMID: 14642973]
[83]
Desta, Z.; Soukhova, N.; Flockhart, D.A. In vitro inhibition of pimozide N-dealkylation by selective serotonin reuptake inhibitors and azithromycin. J. Clin. Psychopharmacol., 2002, 22(2), 162-168.
[http://dx.doi.org/10.1097/00004714-200204000-00009] [PMID: 11910261]
[84]
Roth, B.L.; Craigo, S.C.; Choudhary, M.S.; Uluer, A.; Monsma, F.J., Jr; Shen, Y.; Meltzer, H.Y.; Sibley, D.R. Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J. Pharmacol. Exp. Ther., 1994, 268(3), 1403-1410.
[PMID: 7908055]
[85]
Roberts, A.J.; Hedlund, P.B. The 5-HT7 receptor in learning and memory. Hippocampus, 2012, 22(4), 762-771.
[http://dx.doi.org/10.1002/hipo.20938] [PMID: 21484935]
[86]
Aghajanian, G.; Liu, R.J. Serotonin (5-Hydroxytryptamine; 5-HT): CNS pathways and neurophysiology. Encycloped. Neurosci., 2010, 1, 715-722.
[87]
Gonçalves, J.M.; Silva, C.A.B.; Rivero, E.R.C.; Cordeiro, M.M.R. Inhibition of cancer stem cells promoted by Pimozide. Clin. Exp. Pharmacol. Physiol., 2019, 46(2), 116-125.
[http://dx.doi.org/10.1111/1440-1681.13049] [PMID: 30383889]
[88]
Krummel, T.M.; Neifeld, J.P.; Taub, R.N. Effects of dopamine agonists and antagonists on murine melanoma: Correlation with dopamine binding activity. Cancer, 1982, 49(6), 1178-1184.
[http://dx.doi.org/10.1002/1097-0142(19820315)49:6<1178:AID-CNCR2820490619>3.0.CO;2-H] [PMID: 7059943]
[89]
Shaw, V.; Srivastava, S.; Srivastava, S.K. Repurposing antipsychotics of the diphenylbutylpiperidine class for cancer therapy. Semin. Cancer Biol., 2021, 68, 75-83.
[http://dx.doi.org/10.1016/j.semcancer.2019.10.007] [PMID: 31618686]
[90]
Zhou, W.; Chen, M.K.; Yu, H.T.; Zhong, Z.H.; Cai, N.; Chen, G.Z.; Zhang, P.; Chen, J.J. The antipsychotic drug pimozide inhibits cell growth in prostate cancer through suppression of STAT3 activation. Int. J. Oncol., 2016, 48(1), 322-328.
[http://dx.doi.org/10.3892/ijo.2015.3229] [PMID: 26549437]
[91]
Lee, J.K.; Chang, N.; Yoon, Y.; Yang, H.; Cho, H.; Kim, E.; Shin, Y.; Kang, W.; Oh, Y.T.; Mun, G.I.; Joo, K.M.; Nam, D.H.; Lee, J. USP1 targeting impedes GBM growth by inhibiting stem cell maintenance and radioresistance. Neuro-oncol., 2016, 18(1), 37-47.
[http://dx.doi.org/10.1093/neuonc/nov091] [PMID: 26032834]
[92]
Miracco, C.; Cosci, E.; Oliveri, G.; Luzi, P.; Pacenti, L.; Monciatti, I.; Mannucci, S.; De Nisi, M.C.; Toscano, M.; Malagnino, V.; Falzarano, S.M.; Pirtoli, L.; Tosi, P. Protein and mRNA expression of autophagy gene Beclin 1 in human brain tumours. Int. J. Oncol., 2007, 30(2), 429-436.
[PMID: 17203225]
[93]
Ryskalin, L.; Limanaqi, F.; Biagioni, F.; Frati, A.; Esposito, V.; Calierno, M.T.; Lenzi, P.; Fornai, F. The emerging role of m-TOR up-regulation in brain astrocytoma. Histol. Histopathol., 2017, 32(5), 413-431.
[PMID: 27775777]
[94]
Weissenrieder, J.S.; Reed, J.L.; Green, M.V.; Moldovan, G.L.; Koubek, E.J.; Neighbors, J.D.; Hohl, R.J. The dopamine d2 receptor contributes to the spheroid formation behavior of u87 glioblastoma cells. Pharmacology, 2020, 105(1-2), 19-27.
[http://dx.doi.org/10.1159/000502562] [PMID: 31645049]
[95]
Conde-Estévez, D. Targeted cancer therapy: interactions with other medicines. Clin. Transl. Oncol., 2017, 19(1), 21-30.
[http://dx.doi.org/10.1007/s12094-016-1509-x] [PMID: 27112938]
[96]
Boone, J.L.; Patrone, N.A.; Daugherty, J.E. Disseminated gonococcal infection and acute pericarditis. N. C. Med. J., 1986, 47(10), 466-467.
[PMID: 3466039]
[97]
Khasawneh, F.T.; Shankar, G.S. Minimizing cardiovascular adverse effects of atypical antipsychotic drugs in patients with schizophrenia. Cardiol. Res. Pract., 2014, 2014, 1-8.
[http://dx.doi.org/10.1155/2014/273060] [PMID: 24649390]
[98]
Fleischhaker, C.; Heiser, P.; Hennighausen, K.; Herpertz-Dahlmann, B.; Holtkamp, K.; Mehler-Wex, C.; Rauh, R.; Remschmidt, H.; Schulz, E.; Warnke, A. Weight gain in children and adolescents during 45 weeks treatment with clozapine, olanzapine and risperidone. J. Neural Transm., 2008, 115(11), 1599-1608.
[http://dx.doi.org/10.1007/s00702-008-0105-9] [PMID: 18779922]
[99]
Correll, C.U.; Manu, P.; Olshanskiy, V.; Napolitano, B.; Kane, J.M.; Malhotra, A.K. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA, 2009, 302(16), 1765-1773.
[http://dx.doi.org/10.1001/jama.2009.1549] [PMID: 19861668]
[100]
Guo, J.J.; Wu, J.; Kelton, C.M.L.; Jing, Y.; Fan, H.; Keck, P.E.; Patel, N.C. Exposure to potentially dangerous drug-drug interactions involving antipsychotics. Psychiatr. Serv., 2012, 63(11), 1080-1088.
[http://dx.doi.org/10.1176/appi.ps.201100443] [PMID: 22910806]
[101]
Matos, A.; Bain, K.T.; Bankes, D.L.; Furman, A.; Skalski, B.; Verzicco, J.; Turgeon, J. Cytochrome p450 (cyp450) interactions involving atypical antipsychotics are common in community-dwelling older adults treated for behavioral and psychological symptoms of dementia. Pharmacy, 2020, 8(2), 63.
[http://dx.doi.org/10.3390/pharmacy8020063] [PMID: 32276526]
[102]
March-Vila, E.; Pinzi, L.; Sturm, N.; Tinivella, A.; Engkvist, O.; Chen, H.; Rastelli, G. On the integration of in silico drug design methods for drug repurposing. Front. Pharmacol., 2017, 8, 298.
[http://dx.doi.org/10.3389/fphar.2017.00298] [PMID: 28588497]
[103]
Corsello, S.M.; Bittker, J.A.; Liu, Z.; Gould, J.; McCarren, P.; Hirschman, J.E.; Johnston, S.E.; Vrcic, A.; Wong, B.; Khan, M.; Asiedu, J.; Narayan, R.; Mader, C.C.; Subramanian, A.; Golub, T.R. The drug repurposing hub: A next-generation drug library and information resource. Nat. Med., 2017, 23(4), 405-408.
[http://dx.doi.org/10.1038/nm.4306] [PMID: 28388612]

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