Historically, multiplicity of actions in synthetic compounds is a rule rather than exception. The science of non-
antibiotics evolved in this background. From the
antimalarial and antitrypanosomial
dye methylene blue, chemically similar compounds, the
phenothiazines, were developed. The
phenothiazines were first recognised for their
antipsychotic properties, but soon after their antimicrobial functions came to be known and then such compounds were designated as non-
antibiotics. The emergence of highly
drug-resistant bacteria had initiated an urgent need to search for novel affordable compounds. Several
phenothiazines awakened the interest among scientists to determine their antimycobacterial activity.
Chlorpromazine,
trifluoperazine,
methdilazine and
thioridazine were found to have distinct antitubercular action.
Thioridazine took the lead as researchers repeatedly claimed its potentiality. Although
thioridazine is known for its central nervous system and cardiotoxic side-effects, extensive and repeated in vitro and in vivo studies by several research groups revealed that a very small dose of
thioridazine is required to kill tubercle bacilli inside macrophages in the lungs, where the bacteria try to remain and multiply silently. Such a small dose is devoid of its adverse side-effects. Recent studies have shown that the (-)
thioridazine is a more active
antimicrobial agent and devoid of the toxic side effects normally encountered. This review describes the possibilities of bringing down
thioridazine and its (-) form to be combined with other
antitubercular drugs to treat
infections by
drug-resistant strains of Mycobacterium tuberculosis and try to eradicate this deadly disease.