{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T13:45:34Z","timestamp":1776606334708,"version":"3.51.2"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1AI155319"],"award-info":[{"award-number":["RO1AI155319"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1108452"],"award-info":[{"award-number":["OPP1108452"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Tuberculosis (TB) remains a challenging global health concern and claims more than a million lives every year. We lack an effective vaccine and understanding of what constitutes protective immunity against TB to inform rational vaccine design. Moreover, treatment of TB requires prolonged use of multi-drug regimens and is complicated by problems of compliance and drug resistance. While most\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) bacilli are quickly killed by the drugs, the prolonged course of treatment is required to clear persistent drug-tolerant subpopulations. Mtb\u2019s differential sensitivity to drugs is, at least in part, determined by the interaction between the bacilli and different host macrophage populations. Therefore, to design better treatment regimens for TB, we need to understand and modulate the heterogeneity and divergent responses that Mtb bacilli exhibit within macrophages. However, developing drugs\n                    <jats:italic>de-novo<\/jats:italic>\n                    is a long and expensive process. An alternative approach to expedite the development of new TB treatments is to repurpose existing drugs that were developed for other therapeutic purposes if they also possess anti-tuberculosis activity. There is growing interest in the use of immune modulators to supplement current anti-TB drugs by enhancing the host\u2019s antimycobacterial responses. Ion channel blocking agents are among the most promising of the host-directed therapeutics. Some ion channel blockers also interfere with the activity of mycobacterial efflux pumps. In this review, we discuss some of the ion channel blockers that have shown promise as potential anti-TB agents.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.665785","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T02:34:11Z","timestamp":1624502051000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Something Old, Something New: Ion Channel Blockers as Potential Anti-Tuberculosis Agents"],"prefix":"10.3389","volume":"12","author":[{"given":"Steven C.","family":"Mitini-Nkhoma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth T.","family":"Chimbayo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David T.","family":"Mzinza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David V.","family":"Mhango","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron P.","family":"Chirambo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Mandalasi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agness E.","family":"Lakudzala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dumizulu L.","family":"Tembo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kondwani C.","family":"Jambo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry C.","family":"Mwandumba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e3426","DOI":"10.1371\/journal.pone.0003426","article-title":"Detection and Molecular Characterization of 9000-Year-Old Mycobacterium tuberculosis From a Neolithic Settlement in the Eastern Mediterranean","volume":"3","author":"Hershkovitz","year":"2008","journal-title":"PLoS One"},{"key":"B2","volume-title":"Global Tuberculosis Report 2020","year":"2020"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a017822","article-title":"Tuberculosis Treatment and Drug Regimens","volume":"5","author":"Sotgiu","year":"2015","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1186\/s13104-018-3789-4","article-title":"Non-Adherence to Anti-Tuberculosis Treatment, Reasons and Associated Factors Among TB Patients Attending at Gondar Town Health Centers, Northwest Ethiopia","volume":"11","author":"Mekonnen","year":"2018","journal-title":"BMC Res Notes"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e7482","DOI":"10.1097\/MD.0000000000007482","article-title":"Side Effects Associated With the Treatment of Multidrug-Resistant Tuberculosis at a Tuberculosis Referral Hospital in South Korea: A Retrospective Study","volume":"96","author":"Yang","year":"2017","journal-title":"Medicine (Baltimore)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.11.2217","article-title":"Inhibition of Tubercle Bacilli in Cultured Human Macrophages by Chloroquine Used Alone and in Combination With Streptomycin, Isoniazid, Pyrazinamide, and Two Metabolites of Vitamin D3","volume":"34","author":"Crowle","year":"1990","journal-title":"Antimicrob Agents Chemother"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1159\/000239036","article-title":"Chlorpromazine: A Drug Potentially Useful for Treating Mycobacterial Infections","volume":"38","author":"Crowle","year":"1992","journal-title":"Chemotherapy"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.11.2344","article-title":"Therapy of Multidrug-Resistant Tuberculosis: Lessons From Studies With Mice","volume":"37","author":"Klemens","year":"1993","journal-title":"Antimicrob Agents Chemother"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1355","article-title":"Mycobacterium Tuberculosis Induces Expression of P-glycoprotein in Promonocytic U1 Cells Chronically Infected With HIV Type 1","volume":"199","author":"Gollapudi","year":"1994","journal-title":"Biochem Biophys Res Commun"},{"key":"B10","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/0378-8741(95)01331-8","article-title":"Activity of Bromhexine and Ambroxol, Semi-Synthetic Derivatives of Vasicine From the Indian Shrub Adhatoda Vasica, Against Mycobacterium tuberculosis In Vitro","volume":"50","author":"Grange","year":"1996","journal-title":"J Ethnopharmacol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022992224594","article-title":"An Assessment of the In Vitro Antimicrobial Effects of Two Antiepileptic Drugs - Sodium Valproate and Phenytoin","volume":"83","author":"Esiobu","year":"2003","journal-title":"Antonie van Leeuwenhoek"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.47058-0","article-title":"Activity of Ketoconazole Against Mycobacterium tuberculosis In Vitro and in the Mouse Model","volume":"56","author":"Byrne","year":"2007","journal-title":"J Med Microbiol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201001-0077OC","article-title":"Short, Highly Effective, and Inexpensive Standardized Treatment of Multidrug-Resistant Tuberculosis","volume":"182","author":"Van Deun","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.5740\/jaoacint.12-010","article-title":"Antimycobacterial Effect of Extract and its Components From Rheum Rhaponticum","volume":"96","author":"Smolarz","year":"2013","journal-title":"J AOAC Int"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e1003946","DOI":"10.1371\/journal.ppat.1003946","article-title":"Identification of Host-Targeted Small Molecules That Restrict Intracellular Mycobacterium Tuberculosis Growth","volume":"10","author":"Stanley","year":"2014","journal-title":"PLoS Pathog"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404137","article-title":"Functional Drug Screening Reveals Anticonvulsants as Enhancers of mTOR-Independent Autophagic Killing of Mycobacterium Tuberculosis Through Inositol Depletion","volume":"7","author":"Schiebler","year":"2015","journal-title":"EMBO Mol Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e0149326","DOI":"10.1371\/journal.pone.0149326","article-title":"Ion Channel Blockers as Antimicrobial Agents, Efflux Inhibitors, and Enhancers of Macrophage Killing Activity Against Drug Resistant Mycobacterium tuberculosis","volume":"11","author":"Machado","year":"2016","journal-title":"PLoS One"},{"key":"B18","volume-title":"WHO Treatment Guidelines for Drug-Resistant Tuberculosis\u202f: 2016 Update","year":"2016"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01019-18","article-title":"Ambroxol Induces Autophagy and Potentiates Rifampin Antimycobacterial Activity","volume":"62","author":"Choi","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"B20","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.ijid.2018.02.021","article-title":"Evaluation of the Efficacy of Valproic Acid and Suberoylanilide Hydroxamic Acid (Vorinostat) in Enhancing the Effects of First-Line Tuberculosis Drugs Against Intracellular Mycobacterium tuberculosis","volume":"69","author":"Rao","year":"2018","journal-title":"Int J Infect Dis"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1016\/j.cell.2019.08.004","article-title":"TNF Induces Pathogenic Programmed Macrophage Necrosis in Tuberculosis Through a Mitochondrial-Lysosomal-Endoplasmic Reticulum Circuit","volume":"178","author":"Roca","year":"2019","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.abb.2019.04.006","article-title":"Role of Sirt1 in Innate Immune Mechanisms Against Mycobacterium Tuberculosis Via the Inhibition of TAK1 Activation","volume":"667","author":"Yang","year":"2019","journal-title":"Arch Biochem Biophys"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.15534","article-title":"Use of Calcium Channel Blockers and Risk of Active Tuberculosis Disease: A Population-Based Analysis","volume":"77","author":"Lee","year":"2021","journal-title":"Hypertension"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005926","article-title":"Second Messengers","volume":"8","author":"Newton","year":"2016","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.028","article-title":"Calcium Signaling","volume":"131","author":"Clapham","year":"2007","journal-title":"Cell"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-9-35","article-title":"ATP-Induced Autophagy Is Associated With Rapid Killing of Intracellular Mycobacteria Within Human Monocytes\/Macrophages","volume":"9","author":"Biswas","year":"2008","journal-title":"BMC Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2014.10.030","article-title":"Ion Channels in the Regulation of Apoptosis","volume":"1848","author":"Kondratskyi","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"B28","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1080\/15548627.2017.1384887","article-title":"Ion Channels in the Regulation of Autophagy","volume":"14","author":"Kondratskyi","year":"2018","journal-title":"Autophagy"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2005.06.037","article-title":"Ryanodine Receptors","volume":"38","author":"Hamilton","year":"2005","journal-title":"Cell Calcium"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.4.1499","article-title":"Apoptosis, But Not Necrosis, of Infected Monocytes Is Coupled With Killing of Intracellular Bacillus Calmette-Gu\u00e9rin","volume":"180","author":"Molloy","year":"1994","journal-title":"J Exp Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2016.01.059","article-title":"Efferocytosis","volume":"26","author":"Kumar","year":"2016","journal-title":"Curr Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-6111-1_6","article-title":"Dying to Live: How the Death Modality of the Infected Macrophage Modulates Immunity to Tuberculosis","volume":"783","author":"Divangahi","year":"2013","journal-title":"Adv Exp Med Biol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00089","article-title":"Ryanodine Receptors in Autophagy: Implications for Neurodegenerative Diseases","volume":"12","author":"Vervliet","year":"2018","journal-title":"Front Cell Neurosci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3945\/an.115.011627","article-title":"Resveratrol: How Much Wine do You Have to Drink to Stay Healthy","volume":"7","author":"Weiskirchen","year":"2016","journal-title":"Adv Nutr"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.855","article-title":"Resveratrol: A Miraculous Natural Compound for Diseases Treatment","volume":"6","author":"Koushki","year":"2018","journal-title":"Food Sci Nutr"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/molecules19067327","article-title":"Resveratrol and Calcium Signaling: Molecular Mechanisms and Clinical Relevance","volume":"19","author":"McCalley","year":"2014","journal-title":"Molecules"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.5935\/0103-5053.20160107","article-title":"Synthesis, Antitubercular and Leishmanicidal Evaluation of Resveratrol Analogues","volume":"27","author":"Coimbra","year":"2016","journal-title":"J Braz Chem Soc"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2019.02.015","article-title":"Antibacterial and Antifungal Properties of Resveratrol","volume":"53","author":"Vestergaard","year":"2019","journal-title":"Int J Antimicrob Agents"},{"key":"B39","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s12916-016-0635-1","article-title":"Potential of Immunomodulatory Agents as Adjunct Host-Directed Therapies for Multidrug-Resistant Tuberculosis","volume":"14","author":"Zumla","year":"2016","journal-title":"BMC Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"eaaj1789","DOI":"10.1126\/sciimmunol.aaj1789","article-title":"Host Sirtuin 1 Regulates Mycobacterial Immunopathogenesis and Represents a Therapeutic Target Against Tuberculosis","volume":"2","author":"Cheng","year":"2017","journal-title":"Sci Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB Signaling in Inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct Target Ther"},{"key":"B42","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.163.9.5116","article-title":"Preferential Role for NF-\u03baB\/Rel Signaling in the Type 1 But Not Type2 T Cell-Dependent Immune Response In Vivo","volume":"163","author":"Aronica","year":"1999","journal-title":"J Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"e61925","DOI":"10.1371\/journal.pone.0061925","article-title":"Inhibition of Nuclear Factor-Kappa B Activation Decreases Survival of Mycobacterium Tuberculosis in Human Macrophages","volume":"8","author":"Bai","year":"2013","journal-title":"PLoS One"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e5305","DOI":"10.1371\/journal.pone.0005305","article-title":"Voltage Gated Calcium Channels Negatively Regulate Protective Immunity to Mycobacterium tuberculosis","volume":"4","author":"Gupta","year":"2009","journal-title":"PLoS One"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2018.1536598","article-title":"Autophagy: A New Strategy for Host-Directed Therapy of Tuberculosis","volume":"10","author":"Paik","year":"2019","journal-title":"Virulence"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/conf.fimmu.2015.05.00160","article-title":"Autophagy Inducing Drugs Contribute to Control Mycobacterium Tuberculosis Infection","author":"Ju\u00e1rez","year":"","journal-title":"Front Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2015-0383OC","article-title":"Loperamide Restricts Intracellular Growth of Mycobacterium Tuberculosis in Lung Macrophages","volume":"55","author":"Ju\u00e1rez","year":"2016","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-013-0863-2","article-title":"Verapamil Reverses Cardiac Iron Overload in Streptozocin-Induced Diabetic Rats","volume":"386","author":"Shan","year":"2013","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/nm1542","article-title":"Ca2+ Channel Blockers Reverse Iron Overload by a New Mechanism Via Divalent Metal Transporter-1","volume":"13","author":"Ludwiczek","year":"2007","journal-title":"Nat Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"e1008337","DOI":"10.1371\/journal.ppat.1008337","article-title":"Comprehensive Analysis of Iron Utilization by Mycobacterium Tuberculosis","volume":"16","author":"Zhang","year":"2020","journal-title":"PLoS Pathog"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e47911","DOI":"10.15252\/embr.201947911","article-title":"Iron Overload Inhibits Late Stage Autophagic Flux Leading to Insulin Resistance","volume":"20","author":"Jahng","year":"2019","journal-title":"EMBO Rep"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e02107","DOI":"10.1128\/AAC.02107-17","article-title":"Verapamil Targets Membrane Energetics in Mycobacterium tuberculosis","volume":"62","author":"Chen","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/3767915","article-title":"Ion Transport Modulators as Antimycobacterial Agents","volume":"2020","author":"Mitini-Nkhoma","year":"2020","journal-title":"Tuberc Res Treat"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201304-0650OC","article-title":"Acceleration of Tuberculosis Treatment by Adjunctive Therapy With Verapamil as an Efflux Inhibitor","volume":"188","author":"Gupta","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.4065\/70.3.241","article-title":"Clinical Effects of Intravenously Administered Dantrolene","volume":"70","author":"Wedel","year":"1995","journal-title":"Mayo Clin Proc"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.13.040195.003203","article-title":"Potassium and Calcium Channels in Lymphocytes","volume":"13","author":"Lewis","year":"1995","journal-title":"Annu Rev Immunol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"e89975","DOI":"10.1371\/journal.pone.0089975","article-title":"Physiological Role of Kv1.3 Channel in T Lymphocyte Cell Investigated Quantitatively by Kinetic Modeling","volume":"9","author":"Hou","year":"2014","journal-title":"PLoS One"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.5582\/ddt.2020.03046","article-title":"Targeting Lymphocyte Kv1.3-Channels to Suppress Cytokine Storm in Severe COVID-19: Can it be a Novel Therapeutic Strategy","volume":"14","author":"Kazama","year":"2020","journal-title":"Drug Discov Ther"},{"key":"B59","doi-asserted-by":"publisher","first-page":"eaaw6635","DOI":"10.1126\/scitranslmed.aaw6635","article-title":"Targeting Redox Heterogeneity to Counteract Drug Tolerance in Replicating Mycobacterium Tuberculosis","volume":"11","author":"Mishra","year":"2019","journal-title":"Sci Transl Med"},{"key":"B60","first-page":"1896","article-title":"Chloroquine as a Potential Adjunctive Therapy in Tuberculosis","volume":"44","author":"Matt","year":"2014","journal-title":"Eur Respir J"},{"key":"B61","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.ijantimicag.2017.02.022","article-title":"Chloroquine Enhances the Antimycobacterial Activity of Isoniazid and Pyrazinamide by Reversing Inflammation-Induced Macrophage Efflux","volume":"50","author":"Matt","year":"2017","journal-title":"Int J Antimicrob Agents"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010617-052438","article-title":"The Role of Efflux Pumps in Tuberculosis Treatment and Their Promise as a Target in Drug Development: Unraveling the Black Box","volume":"58","author":"te Brake","year":"2018","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1055\/s-2008-1063858","article-title":"Update on Azole Antifungals","volume":"29","author":"Zonios","year":"2008","journal-title":"Semin Respir Crit Care Med"},{"key":"B64","article-title":"Blockade of HERG and Kv1.5 by Ketoconazole","volume":"286","author":"Dumaine","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2016.00456","article-title":"Pregnane X Receptor (PXR)-Mediated Gene Repression and Cross-Talk of PXR With Other Nuclear Receptors Via Coactivator Interactions","volume":"7","author":"Pavek","year":"2016","journal-title":"Front Pharmacol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.818377","article-title":"A Human Xenobiotic Nuclear Receptor Contributes to Nonresponsiveness of Mycobacterium tuberculosis to the Antituberculosis Drug Rifampicin","volume":"293","author":"Bhagyaraj","year":"2018","journal-title":"J Biol Chem"},{"key":"B67","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1517\/17425255.2016.1121381","article-title":"The Pregnane X Receptor in Tuberculosis Therapeutics","volume":"12","author":"Shehu","year":"2016","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr444","article-title":"Clofazimine: Current Status and Future Prospects","volume":"67","author":"Cholo","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1416951112","article-title":"Clofazimine Shortens the Duration of the First-Line Treatment Regimen for Experimental Chemotherapy of Tuberculosis","volume":"112","author":"Tyagi","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B70","doi-asserted-by":"publisher","first-page":"e4009","DOI":"10.1371\/journal.pone.0004009","article-title":"Clofazimine Inhibits Human Kv1.3 Potassium Channel by Perturbing Calcium Oscillation in T Lymphocytes","volume":"3","author":"Ren","year":"2008","journal-title":"PLoS One"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw395","article-title":"Blockade of the Kv1.3 K+ Channel Enhances BCG Vaccine Efficacy by Expanding Central Memory T Lymphocytes","volume":"214","author":"Singh","year":"2016","journal-title":"J Infect Dis"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.283.6295.825","article-title":"Toxic Hepatitis During Ketoconazole Treatment","volume":"283","author":"Heiberg","year":"1981","journal-title":"Br Med J (Clin Res Ed)"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1136\/thx.50.2.213","article-title":"Hepatotoxicity Caused by the Combined Action of Isoniazid and Rifampicin","volume":"50","author":"Askgaard","year":"1995","journal-title":"Thorax"},{"key":"B74","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.ejphar.2009.12.027","article-title":"Block of Sensory Neuronal Na+ Channels by the Secreolytic Ambroxol Is Associated With an Interaction With Local Anesthetic Binding Sites","volume":"630","author":"Leffler","year":"2010","journal-title":"Eur J Pharmacol"},{"key":"B75","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s13256-015-0588-6","article-title":"Marked Improvement in Autoimmune Pulmonary Alveolar Proteinosis With Severe Hypoxemia in a Patient Treated With Ambroxol: A Case Report","volume":"9","author":"Oda","year":"2015","journal-title":"J Med Case Rep"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2019.4611","article-title":"Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial","volume":"77","author":"Mullin","year":"2020","journal-title":"JAMA Neurol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e32835ea0b2","article-title":"Valproic Acid Pathway: Pharmacokinetics and Pharmacodynamics","volume":"23","author":"Ghodke-Puranik","year":"2013","journal-title":"Pharmacogenet Genomics"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1909696116","article-title":"Valproic Acid Interactions With the NavMs Voltage-Gated Sodium Channel","volume":"116","author":"Zanatta","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1082024","article-title":"Induction of Autophagy by Valproic Acid Enhanced Lymphoma Cell Chemosensitivity Through HDAC-Independent and IP3-Mediated PRKAA Activation","volume":"11","author":"Ji","year":"2015","journal-title":"Autophagy"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2015.00090","article-title":"Mycobacterium tuberculosis Infection Induces HDAC1-Mediated Suppression of IL-12B Gene Expression in Macrophages","volume":"5","author":"Chandran","year":"2015","journal-title":"Front Cell Infect Microbiol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9678098","article-title":"Exploring the Drug Repurposing Versatility of Valproic Acid as a Multifunctional Regulator of Innate and Adaptive Immune Cells","volume":"2019","author":"Soria-Castro","year":"2019","journal-title":"J Immunol Res"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20051110","article-title":"Regulation of Chemokines and Cytokines by Histone Deacetylases and an Update on Histone Decetylase Inhibitors in Human Diseases","volume":"20","author":"Gatla","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1007\/BF03256188","article-title":"Carbamazepine-Provoked Hepatotoxicity and Possible Aetiopathological Role of Glutathione in the Events: Retrospective Review of Old Data and Call for New Investigation","volume":"21","author":"Kalapos","year":"2002","journal-title":"Adverse Drug React Toxicol Rev"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1080\/20009666.2018.1514933","article-title":"Valproic Acid Induced Acute Liver Injury Resulting in Hepatic Encephalopathy- A Case Report and Literature Review","volume":"8","author":"Gayam","year":"2018","journal-title":"J Community Hosp Intern Med Perspect"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2015.11.021","article-title":"Immunomodulatory Effects of Fluoxetine: A New Potential Pharmacological Action for a Classic Antidepressant Drug","volume":"109","author":"Di Rosso","year":"2016","journal-title":"Pharmacol Res"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2018.07.040","article-title":"New Roles of Fluoxetine in Pharmacology: Antibacterial Effect and Modulation of Antibiotic Activity","volume":"123","author":"Karine de Sousa","year":"2018","journal-title":"Microb Pathog"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.9b00179","article-title":"Fluoxetine Inhibits Enterovirus Replication by Targeting the Viral 2C Protein in a Stereospecific Manner","volume":"5","author":"Bauer","year":"2019","journal-title":"ACS Infect Dis"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1124\/mol.114.093104","article-title":"Fluoxetine Blocks Nav1.5 Channels Via a Mechanism Similar to That of Class 1 Antiarrhythmics","volume":"86","author":"Poulin","year":"2014","journal-title":"Mol Pharmacol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3390\/ph4040603","article-title":"Role of 5-HT3 Receptors in the Antidepressant Response","volume":"4","author":"B\u00e9try","year":"2011","journal-title":"Pharmaceuticals"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1126\/science.1261512","article-title":"K2P Channel Gating Mechanisms Revealed by Structures of TREK-2 and a Complex With Prozac","volume":"347","author":"Dong","year":"2015","journal-title":"Science"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01639-16","article-title":"Subcellular Partitioning and Intramacrophage Selectivity of Antimicrobial Compounds Against Mycobacterium Tuberculosis","volume":"61","author":"Schump","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"B92","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/S1734-1140(12)70726-0","article-title":"Chemical Structure of Phenothiazines and Their Biological Activity","volume":"64","author":"Jaszczyszyn","year":"2012","journal-title":"Pharmacol Rep"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1038\/srep27540","article-title":"Pharmacological Exploitation of the Phenothiazine Antipsychotics to Develop Novel Antitumor Agents-A Drug Repurposing Strategy","volume":"6","author":"Wu","year":"2016","journal-title":"Sci Rep"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-8579(00)00343-5","article-title":"Enhancement of Antibiotic Activity Against Poly-Drug Resistant Mycobacterium tuberculosis by Phenothiazines","volume":"17","author":"Viveiros","year":"2001","journal-title":"Int J Antimicrob Agents"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03408-14","article-title":"Sterilizing Activity of Thioridazine in Combination With the First-Line Regimen Against Acute Murine Tuberculosis","volume":"58","author":"Dutta","year":"2014","journal-title":"Antimicrob Agents Chemother"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1529520","article-title":"Methylene Blue-Mediated Photodynamic Therapy Induces Macrophage Apoptosis Via ROS and Reduces Bone Resorption in Periodontitis","volume":"2019","author":"Jiang","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/38.6.1049","article-title":"Inhibition of the Respiration of Multi-Drug Resistant Clinical Isolates of Mycobacterium Tuberculosis by Thioridazine: Potential Use for Initial Therapy of Freshly Diagnosed Tuberculosis","volume":"38","author":"Amaral","year":"1996","journal-title":"J Antimicrob Chemother"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics6010003","article-title":"Thioridazine: A Non-Antibiotic Drug Highly Effective, in Combination With First Line Anti-Tuberculosis Drugs, Against Any Form of Antibiotic Resistance of Mycobacterium tuberculosis Due to its Multi-Mechanisms of Action","volume":"6","author":"Amaral","year":"2017","journal-title":"Antibiotics"},{"key":"B99","doi-asserted-by":"publisher","first-page":"e12640","DOI":"10.1371\/journal.pone.0012640","article-title":"The Antipsychotic Thioridazine Shows Promising Therapeutic Activity in a Mouse Model of Multidrug-Resistant Tuberculosis","volume":"5","author":"van Soolingen","year":"2010","journal-title":"PLoS One"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.665785\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T05:04:54Z","timestamp":1672549494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.665785\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,24]]},"references-count":99,"alternative-id":["10.3389\/fimmu.2021.665785"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.665785","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.740463130.793587255","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,24]]},"article-number":"665785"}}