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

被引：51
作者：
Amaral, Leonard [1 ,2 ]
Viveiros, Miguel [3 ]
机构：
[1] Univ Nova Lisboa, Inst Hyg & Trop Med, P-1349008 Lisbon, Portugal
[2] Univ Szeged, Inst Med Microbiol & Immunobiol, H-6720 Szeged, Hungary
[3] Univ Nova Lisboa, Inst Higiene Med & Trop, Unidade Microbiol Med, Global Hlth & Trop Med, P-1349008 Lisbon, Portugal
来源：
ANTIBIOTICS-BASEL | 2017年 / 6卷 / 01期
关键词：
antibiotic resistant pulmonary tuberculosis; thioridazine; in vitro activity; ex vivo activity; in vivo activity (murine model and human trails); the non-killing macrophage; enhancement of intracellular killing of Mtb by thioridazine; mechanism of actions of thioridazine; IN-VITRO; MENAQUINONE OXIDOREDUCTASE; UNITED-STATES; POTENTIAL USE; EFFLUX PUMPS; PHENOTHIAZINES; THERAPY; CHLORPROMAZINE; INHIBITORS; STRAIN;
D O I：
10.3390/antibiotics6010003
中图分类号：
R51 [传染病];
学科分类号：
100401 ;
摘要：
This review presents the evidence that supports the use of thioridazine (TZ) for the therapy of a pulmonary tuberculosis infection regardless of its antibiotic resistance status. The evidence consists of in vitro and ex vivo assays that demonstrate the activity of TZ against all encountered Mycobacterium tuberculosis (Mtb) regardless of its antibiotic resistance phenotype, as well as in vivo as a therapy for mice infected with multi-drug resistant strains of Mtb, or for human subjects infected with extensively drug resistant (XDR) Mtb. The mechanisms of action by which TZ brings about successful therapeutic outcomes are presented in detail.
引用
收藏
页数：14
相关论文
共 103 条
  • [1] Successful alternative treatment of extensively drug-resistant tuberculosis in Argentina with a combination of linezolid, moxifloxacin and thioridazine
    Abbate, Eduardo
    Vescovo, Marisa
    Natiello, Marcela
    Cufre, Monica
    Garcia, Ana
    Gonzalez Montaner, Pablo
    Ambroggi, Marta
    Ritacco, Viviana
    van Soolingen, Dick
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2012, 67 (02) : 473 - 477
  • [2] Drug Tolerance in Replicating Mycobacteria Mediated by a Macrophage-Induced Efflux Mechanism
    Adams, Kristin N.
    Takaki, Kevin
    Connolly, Lynn E.
    Wiedenhoft, Heather
    Winglee, Kathryn
    Humbert, Olivier
    Edelstein, Paul H.
    Cosma, Christine L.
    Ramakrishnan, Lalita
    [J]. CELL, 2011, 145 (01) : 39 - 53
  • [3] Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis
    Agyeman, Akosua Adom
    Ofori-Asenso, Richard
    [J]. ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS, 2016, 15
  • [4] RETRACTED: The large-conductance Ca2+-activated K+ channel is essential for innate immunity (Retracted article. See vol. 468, 2010)
    Ahluwalia, J
    Tinker, A
    Clapp, LH
    Duchen, MR
    Abramov, AY
    Pope, S
    Nobles, M
    Segal, AW
    [J]. NATURE, 2004, 427 (6977) : 853 - 858
  • [5] EFFECTS OF CHLORPROMAZINE ON THE CELL-ENVELOPE PROTEINS OF ESCHERICHIA-COLI
    AMARAL, L
    LORIAN, V
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1991, 35 (09) : 1923 - 1924
  • [6] SYNERGIC EFFECT OF CHLORPROMAZINE ON THE ACTIVITY OF SOME ANTIBIOTICS
    AMARAL, L
    KRISTIANSEN, J
    LORIAN, V
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1992, 30 (04) : 556 - 558
  • [7] Inhibition of the respiration of multi-drug resistant clinical isolates of Mycobacterium tuberculosis by thioridazine: Potential use for initial therapy of freshly diagnosed tuberculosis
    Amaral, L
    Kristiansen, JE
    Abebe, LS
    Millett, W
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1996, 38 (06) : 1049 - 1053
  • [8] Activity of phenothiazines against antibiotic-resistant Mycobacterium tuberculosis:: a review supporting further studies that may elucidate the potential use of thioridazine as anti-tuberculosis therapy
    Amaral, L
    Kristiansen, JE
    Viveiros, M
    Atouguia, J
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2001, 47 (05) : 505 - 511
  • [9] Enhanced killing of intracellular multidrug-resistant Mycobacterium tuberculosis by compounds that affect the activity of efflux pumps
    Amaral, Leonard
    Martins, Marta
    Viveiros, Miguel
    [J]. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2007, 59 (06) : 1237 - 1246
  • [10] Amaral Leonard, 2015, Recent Pat Antiinfect Drug Discov, V10, P71
12345678910