Abstract: The cardiovascular drug lacidipine (Lc) is known to possess antibacterial activity. Further potentiation of action is possible by synergism between Lc and an antibiotic or a non-antibiotic. The minimum inhibitory concentration (MIC) of antibiotics, Lc and other non-antibiotics were detected by the agar dilution technique in different bacteria. Synergism was determined by disc diffusion assay, the fractional inhibitory concentration (FIC) index through checkerboard assessment and, also, the protective capacity of the combination by administering the drugs along with 50 x LD(50) challenge dose of virulent Salmonella typhimurium in animal experiments. Synergism between Lc and penicillin was found to be statistically significant (P <or= 0.01) when compared with their individual effects. The FIC index of this combination was 0.375, confirming synergism. In vivo tests suggested the statistically significant protection of infected mice with this combination. Lc exhibited synergism when combined with non-antibiotics methdilazine and triflupromazine both in vitro and in vivo. Distinct antimicrobial action of Lc and its subsequent synergism with other drugs can open up the possibility of synthesising new molecules by the structural analyses of these compounds.
Abstract: The appearance of multiresistant bacterial strains coupled with the globally ongoing problem of infectious diseases point to the imperative need for novel and affordable antimicrobial drugs. The antibacterial potential of cardiovascular non-antibiotics such as amlodipine (AML), dobutamine, lacidipine, nifedipine and oxyfedrine has been reported previously. Of these drugs, AML proved to have the most significant antibacterial activity against Gram-positive and Gram-negative bacteria. Time-kill curve studies indicate that this Ca(2+) channel blocker exhibits bactericidal activity against Listeria monocytogenes and Staphylococcus aureus. AML could protect against murine listeriosis and salmonellosis at doses ranging within its maximum recommended human or non-toxic ex vivo dose. AML acts as a 'helper compound' in synergistic combination with streptomycin against several Gram-positive and Gram-negative bacterial strains in vitro as well as in the murine salmonellosis model in vivo. The present review focuses on the possible use of cardiovascular non-antibiotics such as AML as auxiliary compound targets for synergistic combinations in infections and hypertension conditions, rationalised on the basis of the activities of the compounds.
Abstract: Based on clinical, histopathological and serological similarities to human celiac disease (CD), we recently established the rhesus macaque model of gluten sensitivity. In this study, we further characterized this condition based on presence of anti-tissue transglutaminase 2 (TG2) antibodies, increased intestinal permeability and transepithelial transport of a proteolytically resistant, immunotoxic, 33-residue peptide from alpha(2)-gliadin in the distal duodenum of gluten-sensitive macaques.
Abstract: Listeria monocytogenes causes suppurative gastritis in BALB/c mice. We investigated the effect of the antihypertensive drug amlodipine (Aml) on the growth of L. monocytogenes in vitro and in vivo. Aml showed noteworthy inhibitory action (minimum inhibitory concentration, MIC(90) 32 microg/ml) against Listeria strains and demonstrated cidal (minimum bactericidal concentration, MBC 64 microg/ml) activity. Aml administered orally at 2.5 microg/g in female BALB/c mice for 7 days, commencing 4 days before oral challenge (1 x 10(8) CFU/ml with L. monocytogenes ATCC 51774), significantly reduced bacterial counts in the stomach (P < 0.01), liver (P < 0.01), and spleen (P < 0.05), and decreased (P < 0.05) gastric lesions, neutrophilic infiltration, edema, vascular degeneration, and necrosis of gastric tissues. It caused the down-regulation of expression of inflammatory cytokines (IFN-gamma, IL-1 beta, and TNF-alpha) compared to drug-free control. Aml may be used in the presence of an antibiotic as adjunct therapy that boosts the host immunity against Listeria. Further, QSAR studies might contribute in manipulating it as a lead compound for the synthesis of new, more effective non-antibiotics (helper compounds), perhaps devoid of side-effects, that could be recommended as compassionate therapy for listeriosis.
Abstract: A total of nine Listeria monocytogenes strains (seven serotypes) were studied to ascertain whether the non-steroidal anti-inflammatory drug diclofenac (Dc) used in combination with the conventional antilisterial antibiotic gentamicin (Gm) or ampicillin (Am) synergistically augments the efficacy of the antibiotic in vitro.
Abstract: New tools are needed for managing celiac sprue, a lifelong immune disease of the small intestine. Ongoing drug trials are also prompting a search for noninvasive biomarkers of gluten-induced intestinal change. We have synthesized and characterized noninflammatory gluten peptide analogs in which key Gln residues are replaced by Asn or His. Like their proinflammatory counterparts, these biomarkers are resistant to gastrointestinal proteases, susceptible to glutenases, and permeable across enterocyte barriers. Unlike gluten peptides, however, they are not appreciably recognized by transglutaminase, HLA-DQ2, or disease-specific T cells. In vitro and animal studies show that the biomarkers can detect intestinal permeability changes as well as glutenase-catalyzed gastric detoxification of gluten. Accordingly, controlled clinical studies are warranted to evaluate the use of these peptides as probes for abnormal intestinal permeability in celiac patients and for glutenase efficacy in clinical trials and practice.
Abstract: Dendritic cells (DCs) induce innate immune responses by recognizing bacterial LPS through TLR4 receptor complexes. In this study, we compared gene expression profiles of TLR4 knockout (TLR4(neg)) DCs and wild type (TLR4(pos)) DCs after stimulating with LPS. We found that the expression of various inflammatory genes by LPS were TLR4-independent. Among them, interleukin 1 receptor antagonist (IL-1rn) was of particular interest since IL-1rn is a potent natural inhibitor of proinflammatory IL-1. Using RT-PCR, real-time PCR, immunoblotting and ELISA, we demonstrated that IL-1rn was induced by DCs stimulated with LPS in the absence of TLR4. 2-Aminopurine, a pharmacological PKR inhibitor, completely abrogated LPS-induced expression of IL-1rn in TLR4(neg) DCs, suggesting that LPS-induced TLR4-independent expression of IL-1rn might be mediated by PKR pathways. Considering that IL-1rn is a physiological inhibitor of IL-1, TLR4-independent and PKR-dependent pathways might be crucial in counter-balancing proinflammatory effector functions of DCs resulted from TLR4-dependent activation by LPS.
Abstract: Diclofenac sodium (Dc) was found to possess antibacterial activity against both drug-sensitive and drug-resistant clinical isolates of Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Mycobacterium spp., in addition to its potent anti-inflammatory activity. The time-kill curve study indicates that this non-steroidal drug exhibits bactericidal activity against Listeria, E. coli, and M. tuberculosis. The antibacterial activity of Dc comes, in part, from its ability to inhibit the DNA synthesis of E. coli and L. monocytogenes. Dc could protect murine listeriosis, salmonellosis, and tuberculosis at doses ranged within its maximum recommended human or non-toxic ex-vivo dose. Dc possesses anti-plasmid activity and acts as a 'helper compound' in synergistic combination with streptomycin against E. coli and Mycobacterium or gentamicin against Listeria. This review focuses on the possible use of Dc, a non-antibiotic helper compound, in infections and inflammatory conditions, rationalized on the basis of the activities of the compounds.
Abstract: The interactions between nonsteroidal anti-inflammatory drugs (NSAID) and Listeria monocytogenes have not been sufficiently documented to date. The aim of this study was to investigate the possible effects of Diclofenac (Dc) in a murine listerial infection model.
Abstract: Chemotherapy is often futile in systemic listeriosis, translating to being a peril to public health. There is, thus, an imperative need for novel antilisterial compounds, possibly acting through mechanisms dissimilar to those of existing drugs. The present study describes one such agent-the non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium (Dc). The National Committee for Clinical Laboratory Standards (NCCLS) minimum inhibitory concentration (MIC), mode of action, and two mechanisms of action, i.e., on bacterial DNA and membrane, have been characterized with respect to Dc. The drug showed noteworthy inhibitory action (MIC90 = 50 microg/ml) against Listeria strains, demonstrated cidal (minimum bactericidal concentration [MBC]=100 microg/ml) activity, inhibited listerial DNA synthesis (45.48%; incorporation of [methyl-3H] thymidine), and possessed bacterial membrane-damaging activity (37.33%; BacLight assay). Dc could be used as a lead compound for the synthesis of new, more active agents perhaps devoid of side effects. Further, quantitative structure-activity relationship (QSAR) studies will contribute to a new generation of promising adjuvants to existing antilisterial drugs.
Abstract: It is believed today that nucleocapsid protein (N) of severe acute respiratory syndrome (SARS)-CoV is one of the most promising antigen candidates for vaccine design. In this study, three fragments [N1 (residues: 1-422); N2 (residues: 1-109); N3 (residues: 110-422)] of N protein of SARS-CoV were expressed in Escherichia coli and analyzed by pooled sera of convalescence phase of SARS patients. Three gene fragments [N1 (1-1269 nt), N2 (1-327 nt) and N3 (328-1269 nt)-expressing the same proteins of N1, N2 and N3, respectively] of SARS-N were cloned into pVAX-1 and used to immunize BALB/c mice by electroporation. Humoral (by enzyme-linked immunosorbent assay, ELISA) and cellular (by cell proliferation and CD4(+):CD8(+) assay) immunity was detected by using recombinant N1 and N3 specific antigen. Results showed that N1 and N3 fragments of N protein expressed by E. coli were able to react with sera of SARS patients but N2 could not. Specific humoral and cellular immunity in mice could be induced significantly by inoculating SARS-CoV N1 and N3 DNA vaccine. In addition, the immune response levels in N3 were significantly higher for antibody responses (IgG and IgG1 but not IgG2a) and cell proliferation but not in CD4(+):CD8(+) assay compared to N1 vaccine. The identification of antigenic N protein fragments has implications to provide basic information for the design of DNA vaccine against SARS-CoV. The present results not only suggest that DNA immunization with pVax-N3 could be used as potential DNA vaccination approaches to induce antibody in BALB/c mice, but also illustrates that gene immunization with these SARS DNA vaccines can generate different immune responses.
Abstract: The cardiovascular drug lacidipine was screened in vitro for possible antibacterial activity with respect to 389 Gram-positive and Gram-negative bacterial strains. It was noticed that most bacteria (233) failed to grow at 50-200 microg/mL concentrations of the drug. Some strains were inhibited at even lower concentrations. The bacteria could be arranged according to their decreasing order of sensitivity as follows: Staphylococcus aureus, Vibrio cholerae, Salmonella spp., Shigellae, Escherichia coli, Bacillus spp., Klebsiellae and Pseudomonas spp. Lacidipine was found to be bacteriostatic in nature against S. aureus and V cholerae. When administered to Swiss strain of white mice at doses of 30 and 60 microg/mouse, lacidipine significantly protected the animals challenged with 50 MLD of S. typhimurium NCTC 74. According to the chi-square test, the in vivo data were highly significant (p<0.001).
Abstract: Diclofenac sodium (Dc), an anti-inflammatory agent, has remarkable inhibitory action both against drug-sensitive and drug-resistant clinical isolates of various Gram-positive and Gram-negative bacteria. The aim of this study was to determine the ability of Dc to protect mice from a virulent Salmonella infection. Dc injected at 1.5 microg/g and 3.0 microg/g mouse body weight significantly protected animals from the lethality of Salmonella infection. As was the case for the in vitro interaction, Dc in combination with streptomycin was even more effective. The non-antibiotic drug Dc has potential for the management of problematic antibiotic-resistant bacterial infections.
Abstract: The non-steroidal anti-inflammatory drug diclofenac (DCL) shows noteworthy in vitro and in vivo antimycobacterial activity. The aim of this study was to ascertain whether DCL used in combination with the first-line antitubercular antibiotic streptomycin (STM) synergistically augments its efficacy in vitro as well as in a murine tuberculosis infection model. In vitro minimum inhibitory concentrations (MICs) and synergistic activities of the drugs with respect to standard strains and clinical isolates of Mycobacterium tuberculosis were determined. Swiss albino male mice were intravenously infected with 2.3x10(7) M. tuberculosis H37Rv. Mice were treated with DCL or STM alone as well as in combination for 4 weeks to determine the survival rate, spleen weight and colony-forming unit (CFU) counts in the lungs and spleen. DCL was bactericidal at 40 microg/mL (4xMIC) against M. tuberculosis H37Rv and was synergistic with STM in vitro (fractional inhibitory concentration index 0.37). A dose of 10 microg/g/day DCL or 150 microg/g/day STM for 4 weeks, administered from 1 day post infection, significantly (P<0.05) lowered bacterial counts and reduced mean spleen weight of mice compared with untreated animals. Simultaneous administration of both agents further decreased CFU counts (P<0.05) in the lungs and spleen compared with mice receiving STM alone. Thus, the ability of extended antibiotic therapy may be improved with the help of this synergistic drug pair in murine tuberculosis, and further investigations may throw light on new directions to combat multidrug-resistant tuberculosis infections in humans.
Abstract: Thepiperazine chlorcyclizine HCl (CCZ), possessing significant antimetabolic as well as virucidal and virustatic activities against the human immunodeficiency virus (HIV) and other retroviruses, was selected to determine its anticarcinogenic potential The anticancer activity of CCZ was evaluated against procarcinogen n-diethylnitrosamine (NDA)-initiated hepatocarcinogenesis, which was subsequently promoted by phenobarbital (PB) in male Sprague-Dawley rats. The anticancer efficacy of CCZ was monitored by estimating some potential markers of neoplastic and preneoplastic hepatic conditions, e.g., glutathione (GSH), glutathione-S-transferase (GST) and gamma-glutamyl transpeptidase (gammaGTP). CCZ exhibited antineoplastic activity on a long-term therapeutic basis. Furthermore, this drug restricted the exponential increase of the antioxidant markers in the hyperplastic nodule and the surrounding liver tissues in comparison with the carcinogen-controlled rats during the entire period of treatment. A decrease in the number of nodules was observed in the CCZ-treated group.
Abstract: The antipsychotic thioxanthene flupenthixol, possessing a trifluoromethyl substituent at position 2, exhibited a distinct antibacterial property against 352 strains of bacteria from 3 Gram-positive and 13 Gram-negative genera. The minimum inhibitory concentration (MIC) of flupenthixol was determined by the National Committee for Clinical Laboratory Standards agar dilution method. MICs ranged from 10-100 microg/mL in most of the strains, whilst some strains were inhibited at even lower concentrations. The mode of action of this drug was found to be bacteriostatic against Staphylococcus aureus and Vibrio cholerae. In the in vivo experiments, this drug was capable of contributing significant protection (P < 0.001) to a Swiss strain of white mice challenged with 50 median lethal dose of a mouse-virulent strain at a drug concentration of 15 microg/mouse. In addition, flupenthixol remarkably reduced the number of viable bacteria in organ homogenates and blood of mice treated with this drug.
Abstract: E. coli is the main agent of uncomplicated urinary tract infections (UTIs) and accounts for more than 85% of recurrent cystitis and at least 35% of recurrent pyelonephritis. Despite the widespread availability of antibiotics, UTIs remain the most common bacterial infection in the human population. It is currently advised that the clinical administration of antibiotics against the pathogenic bacteria should be prohibitted due to the emergence of multidrug resistant (MDR) bacterial strains. Therefore, newer and more effective antimicrobials are in demand to treat such cases. One hundred and thirty six urine samples were collected from UTI patients. E. coli was isolated from 85 samples, out of which 33% were resistant to common antibiotics. The isolates were decreasingly resistant to ampicillin, tobramycin, augmentin, nalidixic acid, cefuroxime, nitrofurantoin, kanamycin, pipemidic acid, chloramphenicol, cefotaxime, cefamendol, ofloxacin, ceftizoxime, norfloxacin and amikacin. The anti-inflammatory drug diclofenac exhibited significant antibacterial activity against common bacterial strains both in vitro and in vivo. The present work was conducted to evaluate the in vitro inhibitory effect of this drug on the clinically isolated strains of E. coli in hospitals. All the isolates were sensitive to diclofenac, with MIC values ranging from 5-50 microg/mL. The MIC90 value of the drug was 25 microg/mL. Therefore, it may be suggested that diclofenac has the capacity to treat UTI caused by E. coli.
Abstract: The antipsychotic drug prochlorperazine was screened in vitro for possible antimicrobial property against 157 strains of bacteria, belonging to gram positive and gram negative genera. The minimum inhibitory concentration (MIC) of prochlorperazine was determined by agar dilution method, which ranged from 25 to 200 microg/ml with respect to most of the strains. Based on such findings, a further study was undertaken to determine whether the efficacy of this drug could be enhanced in the presence of an antihistaminic agent methdilazine, reported to have remarkable antimicrobial action. Four bacterial strains, sensitive to prochlorperazine as well as to three antibacterial chemotherapeutics, viz., methdilazine, fluphenazine and thioridazine were chosen. Disc diffusion tests with prochlorperazine and methdilazine revealed marked synergism between the combination, compared to their individual effects. The synergism was found to be statistically significant (p<0.01). To assess the degree of synergism, the checkerboard analysis was performed. The FIC index of this combination turned out to be 0.37, which confirmed synergism. Therefore, this synergistic drug combination might open a new therapeutic approach to combat drug-resistance in bacterial infections.
Abstract: Methyl-L-DOPA, an antihypertensive agent, has significant in vitro activity against a variety of atypical mycobacteria such as the Mycobacterium avium complex, M. scrofulaceum, M. xenopi and M. marinum, and rare pathogens like M. fortuitum. In the present investigation, the screening of the in vitro activity was further extended by testing the in vitro activity against a total of 53 different strains of mycobacteria, including 34 clinical isolates of both drug-sensitive and drug-resistant Mycobacterium tuberculosis. Most of the strains were inhibited at 10-25 microg/mL concentrations of the drug. When methyl-L-DOPA was injected into male mice at a concentration of 10 microg/g body weight (20 g each), methyl-L-DOPA significantly protected them when challenged with a 50 median lethal dose of M. tuberculosis H37Rv102. According to the chi2 test, the in vivo data were highly significant (p<0.01).
Abstract: The cardiovascular drug oxyfedrine HCl revealed noteworthy in vitro antibacterial action against 501 strains of Gram positive and Gram negative bacteria. It also offered significant protection to mice challenged with a mouse-virulent bacterial strain. Prompted by such results, the present study was carried out to ascertain whether this drug could augment the efficiency of an antibiotic when used in combination with it. For this purpose, ten bacterial strains were selected, which were sensitive to oxyfedrine as well as to six antibiotics, like benzyl penicillin, chloramphenicol, ciprofloxacin, erythromycin, streptomycin and tetracycline. Distinct and statistically significant (p<0.01) synergism was observed between oxyfedrine and tetracycline by disc diffusion tests, compared with their individual effects. The fractional inhibitory concentration (FIC) index of this combination, evaluated by checkerboard analysis, was 0.37, which confirmed synergism between the pair. This synergistic drug duo was further dispensed to infected mice. The results of the mouse-protection tests advocated that the combination was significantly synergistic (p<0.0001), according to Student's 't' test. Hence, the capacity of extended antibiotic therapy in several microbial diseases may be improved with the help of this synergistic drug pair, and the study might throw light on newer directions to contest drug-resistant bacterial infections.
Abstract: The isoflavonoid compounds 'YS11-YS21' were screened for possible antimicrobial property against 12 known Gram-positive and Gram-negative sensitive bacteria. YS11 and YS16 failed to show antimicrobial activity and YS12, 13, 14, 15, 17, 18 and 20 had moderate antimicrobial action. Compounds YS19 and YS21 showed pronounced antimicrobial property. YS19 and YS21 were then tested in vitro against 214 strains of bacteria from one Gram-positive and six Gram-negative genera. The minimum inhibitory concentration (MIC) of YS19 and YS21 was determined by agar dilution method and ranged from 25 to 200 mg/l in most strains. At concentrations of 30 and 60 microg/mouse these compounds offered significant protection to mice challenged with 50 median lethal dose (MLD) of a virulent strain of Salmonella Typhimurium.
Abstract: The antipsychotic phenothiazine triflupromazine, possessing a methyl-thio substituent at position 10 and a fluorine moiety at position 2, exhibited significant antibacterial activity against 279 strains of Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) of the drug, according to the agar dilution method, was between 2 and 50 microg/ml for Staphylococcus aureus, and 5 and 100 microg/ml for shigellae and vibrios. Triflupromazine, when injected intraperitoneally into Swiss albino mice at a concentration of 30 microg/mouse (20 g), manifested a significant protection to the mice (p<0.001) when they were challenged with 50 median lethal dose (MLD) of Salmonella typhimurium NCTC 74. Moreover, there was a statistically significant reduction in the number of viable bacteria in organ homogenates and blood of mice treated with this phenothiazine compound.
Abstract: The non-steroidal antiinflammatory drug diclofenac sodium exhibited remarkable inhibitory action against both drug sensitive and drug resistant clinical isolates of Mycobacterium tuberculosis, as well as other mycobacteria. This agent was tested in vitro against 45 different strains of mycobacteria, most of which were inhibited by the drug at 10-25 microg/ml concentration. When tested in vivo, diclofenac, injected at 10 mg/kg body weight of a Swiss strain of white mice, could significantly protect them when challenged with a 50 median lethal dose of M. tuberculosis H37 Rv102. According to Chi-square test, the in vivo data were highly significant (P<0.01).
Abstract: Amlodipine, a cardiovascular drug, exhibited remarkable antibacterial action in vitro against 504 bacterial strains belonging to both Gram positive and Gram negative genera, as well as in vivo against a mouse-virulent bacterium. Based on such findings, the present study was undertaken to determine whether the efficacy of this non-antibiotic drug could be enhanced in the presence of any antibiotic. Twelve bacterial strains, sensitive to amlodipine as well as to 6 antibiotics, viz., benzyl penicillin, streptomycin, chloramphenicol, tetracycline, erythromycin and ciprofloxacin were chosen. Disc diffusion test with amlodipine and streptomycin revealed marked synergism between the combination, compared with their individual effects. The synergism was found to be statistically significant (p<0.01). To assess the degree of synergy, the checkerboard analysis was performed. The fractional inhibitory concentration (FIC) index of this combination turned out to be 0.24, which confirmed synergism. This antibiotic-non-antibiotic pair was then administered to mice, challenged with S. typhimurium to determine whether this was effective in vivo. Statistical analysis of the mouse protection tests suggested that the combination was highly synergistic (p<0.001), according to Student's t-test. This synergistic drug combination may help us in enhancing the scope of prolonged antibiotic therapy in various types of infections, and might open a new therapeutic approach to combat drug resistance in bacterial diseases.
Abstract: Several compounds are known to possess antimicrobial activity in addition to their predesignated pharmacological actions. In the present study, dicyclomine hydrochloride, an antispasmodic drug, was tested for possible antimicrobial property in vitro and in vivo.
Abstract: Ten cardiovascular drugs, having diverse pharmacological action, were screened for possible antimicrobial property against known eight sensitive bacteria, belonging to Gram positive and Gram negative types. Although five drugs failed to show antimicrobial activity and three had moderate antimicrobial action, oxyfedrine HCl and dobutamine were seen to possess pronounced antimicrobial property. Oxyfedrine was further tested in vitro against 471 strains of bacteria from two Gram positive and fourteen Gram negative genera. The minimum inhibitory concentration (MIC) of oxyfedrine was determined by agar dilution method, which ranged from 50-200 microg/ml in most of the strains, while some strains were inhibited at even lower concentrations. In animal experiments, this compound was capable of offering significant protection to Swiss strain of white mice, challenged with 50 median lethal dose (MLD) of a virulent strain of Salmonella typhimurium at concentrations of 15, 30 and 60 microg/mouse. The in vivo results were highly significant according to chi-square test.
Abstract: Ten cardiovascular drugs were procured in pure form from their manufacturers in India and screened for antimicrobial property against fifteen known bacteria belonging to both gram-positive and gram-negative types. These bacteria were inhibited by the common antibiotics at 1-5 mg ml(-1) level through our earlier studies. Since most of the bacteria were moderate to highly responsive to amlodipine, this compound was further tested in vitro against 504 bacteria comprising 4 genera of gram-positive and 15 genera of gram-negative bacteria. Most of these were inhibited by the drug at 50-200 microg ml(-1) level and few strains were sensitive even at lower concentrations (10 microg ml(-1)). The bacteria could be arranged in the decreasing order of sensitivity towards amlodipine in the following manner: Staphylococcus aureus, Vibrio cholerae, Vibrio parahemolyticus, Shigella spp., Salmonella spp., Bacillus spp., whereas Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa were found to be resistant to the lower concentrations of the drug. Amlodipine was found to be bactericidal in nature when its mode of action was studied against S. aureus 6571, V. cholerae 14035 and Sh boydii 8 NCTC 254/66. The antibacterial activity of amlodipine could also be confirmed in vivo. When it was given to Swiss strain of white mice at different dosages (30 and 60 microg/mouse), it could significantly protect the animals challenged with 50 MLD of Salmonella typhimurium NCTC 74. According to Chi square test the in vivo data were highly significant (p<0.001).