PHARMACEUTICAL COMPOSITIONS CONTAINING CALCIUM CHANNEL BLOCKERS FOR TREATMENT OF TUBERCULOSIS

摘要

The present invention provides calcium channel blockers for the treatment of drug sensitive and drug resistant Mycobacterium tuberculosis infection in humans and animals. In the present invention the role of L-type and R-type VGCC in M. tb infection in vitro and in vivo is disclosed. Inhibiting VGCC in DCs increases calcium influx and activates T cells that mediate killing of M. tb inside macrophages. Likewise, blocking VGCC in infected macrophages and PBMCs induces calcium influx and killing of M. tb. Blocking VGCC in vivo in M. tb infected mice using specific antibodies significantly reduces bacterial loads. Treatment of M. tb infected mice with conventional anti-TB drugs supplemented with a conventional calcium channel blockers such as amlodipine, S-amlodipine and nifedipine mediates a reduction in bacterial loads that is significantly better than drug treatment alone. In addition, these calcium channel blockers effectively kill single, multiple and extensively drug resistant stains of M. tb. Histology of spleen of different treatments indicates a marked improvement in granuloma composition with a significant decrease in cavity formation and restoration of protective granuloma architecture.