Table 1.
Progress towards clinical use of ion channel blockers as anti-tuberculosis agents.
| Year | Milestone | Reference |
|---|---|---|
| 1990 | Crowle and May demonstrated that chloroquine inhibits Mtb growth in macrophage cultures and potentiates streptomycin, pyrazinamide and isoniazid | (6) |
| 1992 | Crowle and colleagues observed that chlorpromazine was more active against Mtb in macrophage cultures than in broth | (7) |
| 1993 | Klemens and colleagues reported that clofazimine was effective against an MDR-TB strain in mice | (8) |
| 1994 | Gollapudi and colleagues demonstrated that verapamil improves accumulation of INH in Mtb-infected macrophages and promotes sensitivity of Mtb to INH | (9) |
| 1996 | Grange and Snell demonstrated that ambroxol has antimycobacterial activity in macrophages | (10) |
| 2003 | Esiobu and Hoosein observed that sodium valproate inhibits growth of Mycobacterium smegmatis in broth | (11) |
| 2007 | Byrne and colleagues observed that ketoconazole was synergistic with rifampicin-isoniazid-pyrazinamide | (12) |
| 2010 | van Deun and colleagues successfully used clofazimine as part of a 9-month MDR-TB treatment regimen in a clinical trial | (13) |
| 2013 | Smolarz and colleagues demonstrated that resveratrol has antitubercular activity in broth | (14) |
| 2014 | Stanley and colleagues demonstrated that fluoxetine promotes autophagic control of Mtb in macrophages | (15) |
| 2015 | Schiebler and colleagues successfully reduced the bacteria burden in mice infected with MDR-TB using carbamazepine and valproic acid | (16) |
| 2016 | Machado and colleagues successfully used verapamil, thioridazine and chlorpromazine to decrease bacteria burden in Mtb-infected macrophages | (17) |
| 2016 | WHO conditionally recommended a short course MDR-TB treatment regimen containing clofazimine | (18) |
| 2018 | Choi and colleagues demonstrated that ambroxol promotes autophagy and potentiates rifampicin in murine models of TB | (19) |
| 2018 | Rao and colleagues demonstrated that sodium valproate has antimycobacterial activity in broth and in macrophages in culture, and enhances activity of rifampicin and isoniazid | (20) |
| 2019 | Roca and colleagues demonstrated that dantrolene inhibits necrotic death and promotes Mtb control in Mtb-infected macrophages | (21) |
| 2019 | Yang and colleagues demonstrated that resveratrol has antitubercular activity in mice | (22) |
| 2021 | Lee and colleagues observed that the use of calcium channel blockers was associated with a 32% decrease in the risk of active tuberculosis | (23) |