Therapy of XDR TB with thioridazine a drug beyond patent protection but eligible for patent "as new use"

Recent Patents on Anti-Infective Drug Discovery

Volumn 5, Issue 2, 2010, Pages 109-114

  Amaral, Leonard ^a   Molnar, Joseph ^b  

^a INSTITUTO DE HIGIENE E MEDICINA TROPICAL   (Portugal)

^b UNIVERSITY OF SZEGED   (Hungary)

Author keywords

Extremely drug resistant tuberculosis xdrtb ; Multi drug resistant tuberculosis mdrtb ; Phenothiazines; Therapy; Thioridazine

Indexed keywords

ANTIBIOTIC AGENT; CHLORPROMAZINE; ISONIAZID; OUABAIN; PHENOTHIAZINE DERIVATIVE; RIFAMPICIN; THIORIDAZINE;

AGRANULOCYTOSIS; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ARTICLE; BACTERIAL STRAIN; CARDIOTOXICITY; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG SAFETY; HEART VENTRICLE TACHYCARDIA; HUMAN; HYDROLYSIS; LUNG TUBERCULOSIS; MACROPHAGE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PATENT; PHAGOSOME; PHARMACODYNAMICS; PHOTOTOXICITY; PRIORITY JOURNAL; QT PROLONGATION; RECOMMENDED DRUG DOSE; RETINOPATHY; SOMNOLENCE;

ADJUVANTS, PHARMACEUTIC; ANIMALS; ANTITUBERCULAR AGENTS; COMPASSIONATE USE TRIALS; DRUG RESISTANCE, MULTIPLE, BACTERIAL; DRUG THERAPY, COMBINATION; EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS; HUMANS; MICE; MYCOBACTERIUM TUBERCULOSIS; PATENTS AS TOPIC; THIORIDAZINE; TUBERCULOSIS, PULMONARY;

EID: 77954066432     PISSN: 1574891X     EISSN: None     Source Type: Journal    
DOI: 10.2174/157489110791233540     Document Type: Article

References (74)

1. Drobniewski FA, Balabanova YM. The diagnosis and management of multiple-drug-resistant-tuberculosis at the beginning of the new millenium. Int J Infect Dis 2002; 6 (Suppl 1): S21-31.
2. WHO/IUATLD Global project on anti-tuberculosis drug resistancesurveillance. Fourth Global report, Geneva 2008.
3. Centers for Disease Control and Prevention [CDC]. Plan to combatextensively drug-resistant tuberculosis: Recommendations of the Federal Tuberculosis Task Force. MMWR Recomm Rep 2009;58 [RR-3]: 1-43.
4. Ehrlich P. The collected papers of Paul Erhlich. In: Himmelweit F,Marquart M, Dale H, Eds. Pergammon Press: London 1956; 500-8.
5. Guttmann P, Erhlich P. Uber die wirkung des methylenblau beimalaria. Berliner Klinische Wochenschrift 1891; 39: 953-6.
6. Amaral L, Viveiros M, Molnar J. Antimicrobial activity ofphenothiazines. In Vivo 2004; 18: 725-32.
7. Kristiansen JE, Amaral L. The potential management of resistantinfections with non-antibiotics. J Antimicrobial Chemother 1997;40: 319-27.
8. Charpentier P, Gaillot P, Jacob R, Gaudechon J, Buisson P.Recherches sur les dimethylaminopropyl N-phenothiazines.Comptes Rendue Aux Academie Des Sci 1952; 235: 59-60.
9. Amaral L, Viveiros M, Kristiansen JE. Phenothiazines: Potentialalternatives for the management of antibiotic resistant infections oftuberculosis and malaria in developing countries. Trop Med IntHealth 2001; 6: 1016-22.
10. Amaral L, Kristiansen JE, Viveiros M, Atouguia J. Activity ofphenothiazines against antibiotic resistant Mycobacteriumtuberculosis: A review supporting further studies that mayelucidate the potential use of Thioridazine as an anti-TB agent. JAntimicrobial Chemother 2001; 47: 505-7.
11. Kristiansen JE, Vergmann B, The antibacterial effect of selectedphenothiazines and thioxanthenes on slow-growing mycobacteria.Acta Pathol Microbiol Immunol Scand B 1986; 94: 393-8.
12. Meindl W, Laske R. Antimycobacterial properties of phenothiazinetype compounds. Arch Pharm Weinheim 1989; 322: 133-6.
13. Chakrabarty AN, Bhattacharya CP, Dastidar SG. Antimycobacterial activity of methdilazine [Md], an antimicrobic phenothiazine. APMIS 1993; 101(6): 449-54.
14. Libenson VS, Braude VI. The antitubercular effect of aminazin.Biull Eksp Biol Med. 1967; 63: 61-3.
15. Molnár J, Béládi I, Földes I. Studies on antituberculotic action ofsome phenothiazine derivatives in vitro. Zentralbl Bakteriol Orig A 1977; 239: 521-6.
16. Amaral L, Kristiansen JE, Abebe LS, Millett W. Inhibition of therespiration of multi-drug resistant clinical isolates of Mycobac-terium tuberculosis by thioridazine: Potential use for initial therapyof freshly diagnosed tuberculosis. J Antimicrob Chemother 1996;38: 1049-53.
17. Bettencourt MV, Bosne-David S, Amaral L. Comparative in vitroactivity of phenothiazines against multidrug-resistant Mycobac-terium tuberculosis. Int J Antimicrob Agents 2000; 16: 69-71.
18. Viveiros M, Amaral L. Enhancement of antibiotic activity againstpoly-drug resistant Mycobacterium tuberculosis by phenothiazines.Int J Antimicrob Agents 2001; 17: 225-8.
19. Crowle AJ, Douvas GS, May MH. Chlorpromazine: A drug poten-tially useful for treating mycobacterial infections. Chemotherapy1992; 38: 410-9.
20. Ordway D, Viveiros M, Leandro C, Jorge AM, Molnar J,Kristiansen JE, et al. Chlorpromazine has intracellular killingactivity against phagocytosed Staphylococcus aureus at clinicalconcentrations. J Infect Chemother 2002; 8: 227-31.
21. Ordway D, Viveiros M, Leandro C, Arroz MJ, Amaral L.Intracellular activity of clinical concentrations of phenothiazinesincluding thioridiazine against phagocytosed Staphylococcusaureus. Int J Antimicrob Agents 2002; 20: 34-43.
22. Martins M, Bleiss W, Marko A, Ordway D, Viveiros M, LeandroC, et al. Clinical concentrations of thioridazine enhance the killingof intracellular methicillin-resistant Staphylococcus aureus: An invivo, ex vivo and electron microscopy study. In Vivo 2004; 18:787-94.
23. Ordway D, Viveiros M, Leandro C, Amaral L. Clinicalconcentrations of Thioridazine kill intracellular Multi-drug resistantMycobacterium tuberculosis. Antimicrob Agents Chemother 2003;47: 917-22.
24. Martins M., Viveiros M, Ramos J, Couto I, Molnar J, Boeree M,et al. SILA 421, an inhibitor of efflux pumps of cancer cells,enhances the killing of intracellular extensively drug-resistanttuberculosis [XDR-TB]. Int J Antimicrob Agents 2009 [Epubahead of print].
25. Martins M, Viveiros M, Kristiansen JE, Molnar J, Amaral L. Thecurative activity of thioridazine on mice infected with Myco-bacterium tuberculosis. In Vivo 2007; 21: 771-5.
26. van Sooligen D, Pando RH, Orozco H, Aguilar D, Magis C, vanIngen J, Thioridazine shows promising activity in a murinemodel of multi-drug resistant tuberculosis. Non-published obser-vations.
27. Weinstein EA, Yano T, Li LS, Avarbock D, Avarbock A, Helm D., Inhibitors of type II NADH: Menaquinone oxidoreductaserepresent a class of antitubercular drugs. Proc Natl Acad Sci USA2005; 102: 4548-53.
28. Thanacoody HK. Thioridazine: Resurrection as an antimicrobialagent? Br J Clin Pharmacol 2007; 64: 566-74.
29. Motohashi N. Phenothiazines and calmodulin [review]. AnticancerRes 1991; 11: 1125-64.
30. Hidaka H, Naito Y. Inhibitor of calmodulin and calmodulindependent enzyme. Tanpakushitsu Kakusan Koso 1998; 43(Suppl12): 1732-8.
31. MacNeil S, Lakey T, Tomlinson S. Calmodulin regulation ofadenylate cyclase activity. Cell Calcium 1985; 6: 213-6.
32. Tate CA, Hyek MF, Taffet GE. The role of calcium in theenergetics of contracting skeletal muscle. Sports Med 1991; 12:208-17.
33. Matschinsky FM. Banting Lecture 1995. A lesson in metabolicregulation inspired by the glucokinase glucose sensor paradigm.Diabetes 1996; 45: 223-41.
34. Reddy PT, Prasad CR, Reddy PH, Reeder D, McKenney K, JaffeH, et al. Cloning and expression of the gene for a novel proteinfrom Mycobacterium smegmatis with functional similarity toeukaryotic calmodulin. J Bacteriol 2003; 185: 5263-8.
35. Sarma PV, Sarma PU, Murthy PS. Isolation, purification andcharacterization of intracellular calmodulin like protein [CALP]from Mycobacterium phlei. FEMS Microbiol Lett 1998; 159: 27-34.
36. Teh JS, Yano T, Rubin H. Type II NADH: Menaquinoneoxidoreductase of Mycobacterium tuberculosis. Infect Disord DrugTargets 2007; 7: 169-81.
37. Zhu L, Zhang Y, Teh JS, Zhang J, Connell N, Rubin H, et al.Characterization of mRNA interferases from Mycobacteriumtuberculosis. J Biol Chem 2006; 281: 18638-43.
38. Yano T, Li LS, Weinstein E, Teh JS, Rubin H. Steady-state kineticsand inhibitory action of antitubercular phenothiazines onMycobacterium tuberculosis type-II NADH-menaquinoneoxidoreductase [NDH-2]. J Biol Chem 2006; 281:11456-63.
39. Avarbock A, Avarbock D, Teh JS, Buckstein M, Wang ZM, RubinH. Functional regulation of the opposing [p]ppGppsynthetase/hydrolase activities of RelMtb from Mycobacteriumtuberculosis. Biochemistry 2005; 44: 9913-23.
40. Wójcikowski J, Daniel WA. Thioridazine-fluoxetine interaction atthe level of the distribution process in vivo. Pol J Pharmacol 2002;54: 647-54.
41. Daniel WA, Wójcikowski J, Pa ucha A. Intracellular distribution ofpsychotropic drugs in the grey and white matter of the brain: Therole of lysosomal trapping. Br J Pharmacol 2001; 134: 807-14.
42. Wójcikowski J, Daniel WA. Distribution interactions betweenperazine and antidepressant drugs. in vivo studies. Pol J Pharmacol 2000; 52: 449-57.
43. Daniel WA, Wójcikowski J. Lysosomal trapping as an importantmechanism involved in the cellular distribution of perazine and inpharmacokinetic interaction with antidepressants. EurNeuropsychopharmacol 1999; 9: 483-91.
44. Drug-drug interactions affected by the transporter protein, P-glycoprotein [ABCB1, MDR1] II. Clinical aspects. Drug DiscovToday 2007; 12: 838-43.
45. Aszalos A. Drug-drug interactions affected by the transporterprotein, P-glycoprotein [ABCB1, MDR1] I. Preclinical aspects.Drug Discov Today 2007; 12: 833-7.
46. Liang XJ, Aszalos A. Multidrug transporters as drug targets. CurrDrug Targets 2006; 7: 911-21.
47. + channel and IKr of guinea pig cardiomyocytes byantipsychotic drug trifluoperazine. J Pharmacol Exp Ther 2005;313: 888-95.
48. Landwojtowicz E, Nervi P, Seelig A. Real-time monitoring of P-glycoprotein activation in living cells. Biochemistry 2002; 41:8050-7.
49. 2+fluxes in brain microsomes by K+ and Na+: Modulation bysulfated polysaccharides and trifluoperazine. J Neurochem 1996;66: 772-8.
50. Adhikary G, Nandy P, Chandra S, Sikdar R, Sen PC. The in vivoinhibition of transport enzyme activities in different organs of ratby chlorpromazine is reversible. Biochem Int 199; 25: 951-61.
51. Mazumder B, Mukherjee S, Sen PC. The chlorpromazine inhibitionof transport ATPase and acetylcholinesterase activities in themicrosomal membranes of rat in vitro and in vivo. Mol CellBiochem 1990; 95: 13-20.
52. +-ATPase pumping and solute transport in rat hepatocytes.Am J Physiol 1987; 253 [5 Pt 1]: G613-21.
53. Amaral L, Engi H, Viveiros M, Molnar J. Comparison of multidrugresistant efflux pumps of cancer and bacterial cells with respect tothe same inhibitory agents. In Vivo 2007; 21: 237-44.
54. Segal AW. How neutrophils kill microbes. Annu Rev Immunol 2005; 23: 197-223.
55. + channel isessential for innate immunity. Nature 2004; 427: 853-8.
56. Reeves EP, Lu H, Jacobs HL, Messina CG, Bolsover S, Gabella G,et al. Killing activity of neutrophils is mediated through activationof proteases by K+ flux. Nature 2002; 416: 291-7.
57. +-ATPase emergesas an interesting drug target. J Intern Med 2007; 261: 44-52.
58. Amaral L, Martins M, Viveiros M. Enhanced killing of intracellularmultidrug-resistant Mycobacterium tuberculosis by compounds thataffect the activity of efflux pumps. J Antimicrob Chemother 2007;59: 123712-46.
59. +transport enhance intracellular killing of M. tuberculosis by non-killing macrophages. In Vivo 2008; 22: 69-75.
60. Martins M, Viveiros M, Couto I, Amaral L. Targetting the humanmacrophages for enhanced killing of intracellular XDT-TB andMDR-TB. Int J Tuberc Lung Dis 2009;13: 1-5.
61. Kirchner V, Kelly CA, Harvey RJ. Thioridazine for dementia.Cochrane Database Syst Rev 2001; 3: CD000464
62. Mackin P. Cardiac side effects of psychiatric drugs. HumPsychopharmacol 2008; 23 (Suppl 1): 3-14.
63. Zemrak WR, Kenna GA. Association of antipsychotic andantidepressant drugs with Q-T interval prolongation. Am J HealthSyst Pharm 2008; 65: 1029-38.
64. Zemrak WR, Kenna GA. Association of antipsychotic andantidepressant drugs with Q-T interval prolongation. Am J HealthSyst Pharm 2008; 65: 1029-38.
65. Delieu JM, Horobin RW, Duguid JK. Formation of immatureneutrophil leucocytes in schizophrenic patients treated with variousantipsychotic drugs: comparisons and predictions. JPsychopharmacol 2006; 20: 824-8.
66. Gongadze N, Kezeli T, Antelava N. Prolong QT interval andtorsades de pointes associated with different group of drugs.Georgian Med News 2007; 45-9.
67. Migliori GB, Lange C, Centis R, Sotgiu G, Mütterlein R, Hoffmann H, et al. TBNET Study Group. Resistance to second-lineinjectables and treatment outcomes in multidrug-resistant andextensively drug-resistant tuberculosis cases. Eur Respir J 2000;31: 1155-59.
68. Migliori GB, Lange C, Girardi E, Centis R, Besozzi G, Kliiman K, et al. SMIRA/TBNET study group. Extensively drug-resistanttuberculosis is worse than multidrug-resistant tuberculosis:Different methodology and settings, same results. Clin Infect Dis 2008; 46: 958-9.
69. Kim HR, Hwang SS, Kim HJ, Lee SM, Yoo CG, Kim YW, et al.Impact of extensive drug resistance on treatment outcomes in non-HIV-infected patients with multidrug-resistant tuberculosis. ClinInfect Dis 2007; 45: 1290-5.
70. TBTC Study 24: Intermittent treatment of TB with isoniazidresistance or intolerance. Center for disease control and prevention;clinical trials. Gov Identifier: NCT00023374 (2007).
71. Abbate E, Vescovo M, Natiello M, Cufre M, Garcia A, AmbroggiM, et al. Tuberculosis extensamente resistente (XDR TB) enArgentina: Aspectos destacables epidemiologicos, bacteriologicos,terapeuticos, y evolutivos. Rev Argentina Med Respir 2007; 1: 19-25.
72. Amaral L, Boeree M, Gillespie SH, Udwadia ZF, van Soolingen D.Thioridazine cures XDR TB and the need for global trials is now!Int J Antimicrob Agents 2009; In Press.
73. Pozuelo, J. Method of pharmacologically treating schizophreniawith alpha-methyl-para-tyrosine. US4165382 (1979).
74. Sandoz-Wander, Inc. Enhanced learning ability by use ofthioridazine. US3879552 (1975).