THE ANTIDEPRESSANT DRUG DOXEPIN: A PROMISING ANTIOXIDANT

ABSTRACTObjective: Oxidative stress contributes to the pathophysiology of exposure to environmental pollutants and to different free radical generatingbiochemical reactions in a human system leading to various types of age-related ailments. An antioxidant is a substance capable of preventingor slowing down oxidation of other molecules. Administration of different natural or synthetic antioxidants can ably lead to prevention andattenuation of such stress-induced biochemical alterations. Best examples of natural antioxidants are plant-derived flavonoids. The presentstudy has been designated to determine antioxidant properties in antidepressant compound doxepin which is structurally similar to flavonoidquercetin.Methods: Antioxidant capacity in doxepin was determined with help of several standard conventional procedures such as phosphomolybdenumassay, Ferric ion and cupric ion reducing power assays, ferrous ion chelating activity assay, hydrogen peroxide, and nitric oxide scavenging activityassays.Results: Doxepin showed a stable rise in its antioxidant activity in a dose-dependent manner as determined by ferric as well as cupric ion reducingcapacity and by phosphomolybdenum assay. An almost identical observation was noted while determining ferrous ion chelating activity. Furthermore,doxepin showed a strong nitric oxide scavenging activity in all the concentrations used in the study while its hydrogen peroxide scavenging activitywas only observed at 500 μg/ml of doxepin.Conclusion: Thus, our study opens up a new vista in search for antioxidants not only from plant sources but also from clinically establishedpharmaceutical compounds that are already in practical use among patients.Keywords: Antioxidant, Antidepressant, Doxepin, Quercetin, Flavanol, Flavonoids

Phenothiazines as a solution for multidrug resistant tuberculosis: From the origin to present

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. [Int Microbiol 2015; 18(1):1-12]Keywords: Mycobacterium tuberculosis · phenotiazines · thioridazine · tuberculosi

Phenothiazines as a solution for multidrug resistant tuberculosis:From the origin to present

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. [Int Microbiol 2015; 18(1):1-12]Keywords: Mycobacterium tuberculosis · phenotiazines · thioridazine · tuberculosi

Diclofenac in the Management of E. coli Urinary Tract Infections

E. coli is the main agent of uncomplicated urinarytract infections (UTIs) and accounts for more than 85% ofrecurrent cystitis and at least 35% of recurrent pyelonephritis.Despite the widespread availability of antibiotics, UTIs remainthe most common bacterial infection in the human population.It is currently advised that the clinical administration ofantibiotics against the pathogenic bacteria should beprohibitted due to the emergence of multidrug resistant (MDR)bacterial strains. Therefore, newer and more effectiveantimicrobials are in demand to treat such cases. One hundredand thirty six urine samples were collected from UTI patients.E. coli was isolated from 85 samples, out of which 33% wereresistant to common antibiotics. The isolates were decreasinglyresistant to ampicillin, tobramycin, augmentin, nalidixic acid,cefuroxime, nitrofurantoin, kanamycin, pipemidic acid,chloramphenicol, cefotaxime, cefamendol, ofloxacin,ceftizoxime, norfloxacin and amikacin. The anti-inflammatorydrug diclofenac exhibited significant antibacterial activityagainst common bacterial strains both in vitro and in vivo. Thepresent work was conducted to evaluate the in vitro inhibitoryeffect of this drug on the clinically isolated strains of E. coli inhospitals. All the isolates were sensitive to diclofenac, withMIC values ranging from 5-50 ?g/mL. The MIC90 value of thedrug was 25 ?g/mL. Therefore, it may be suggested thatdiclofenac has the capacity to treat UTI caused by E. coli.7p

Role of Phenothiazines and Structurally Similar Compounds of Plant Origin in the Fight against Infections by Drug Resistant Bacteria

Phenothiazines have their primary effects on the plasma membranes of prokaryotes and eukaryotes. Among the components of the prokaryotic plasma membrane affected are efflux pumps, their energy sources and energy providing enzymes, such as ATPase, and genes that regulate and code for the permeability aspect of a bacterium. The response of multidrug and extensively drug resistant tuberculosis to phenothiazines shows an alternative therapy for the treatment of these dreaded diseases, which are claiming more and more lives every year throughout the world. Many phenothiazines have shown synergistic activity with several antibiotics thereby lowering the doses of antibiotics administered to patients suffering from specific bacterial infections. Trimeprazine is synergistic with trimethoprim. Flupenthixol (Fp) has been found to be synergistic with penicillin and chlorpromazine (CPZ); in addition, some antibiotics are also synergistic. Along with the antibacterial action described in this review, many phenothiazines possess plasmid curing activities, which render the bacterial carrier of the plasmid sensitive to antibiotics. Thus, simultaneous applications of a phenothiazine like TZ would not only act as an additional antibacterial agent but also would help to eliminate drug resistant plasmid from the infectious bacterial cells

Effect of <i>Mesua ferrea</i> Linn. flower extract on <i>Salmonella</i>

566-568Based on its traditional uses in folk medicine, the whole flower extract of Mesua ferrea Linn. was tested for its in vitro antimicrobial efficacy against five different strains of Salmonella spp. All the strains were found to be highly sensitive to the extract. MIC of the extract against each organism being 50 μg/ml. The extract was tested in vitro for its mode of antibacterial activity against S. Typhimurium NCTC 74 and it was found to be bactericidal in action. In vivo studies of this extract offered significant protection to Swiss albino mice at doses ≈ 2 and 4 mg/mouse when challenged with 50 median lethal dose of S. Typhimurium NCTC 74. Further, the ex tract caused statistically significant reduction in viable count of the strain in liver, spleen and heart blood of challenged mice