Potential role of the cardiovascular non-antibiotic (helper compound) amlodipine in the treatment of microbial infections: scope and hope for the future.

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.

Experimental analyses of synergistic combinations of antibiotics with a recently recognised antibacterial agent, lacidipine.

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

In vitro and in vivo efficacies of amlodipine against Listeria monocytogenes.

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.

The anti-inflammatory drug Diclofenac retains anti-listerial activity in vivo.

AIMS: 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. METHODS AND RESULTS: Dc was administered orally at 2.5 mug g(-1) to female albino strain of laboratory mouse (BALB/c) thrice postinfection (1 x 10(8) CFU ml(-1) oral challenge with L. monocytogenes ATCC 51774), which resulted in significantly (P < 0.01) reduced bacterial counts in liver and spleen, decreased (10-fold, P < 0.05) hepatic colonization and necrosis, and caused up-regulation of the expression of inflammatory cytokines (interferon-gamma, interleukin-1beta, tumour necrosis factor-alpha), compared with drug-free control. CONCLUSIONS: Dc may be useful as a promising adjuvant to the existing therapies in controlling systemic listerial infection. Further, quantitative structure-activity relationship studies might contribute in manipulating it as a lead compound for the synthesis of new, more effective nonantibiotics, perhaps, devoid of side-effects that could be recommended as a compassionate therapy for listeriosis. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first in vivo study designed to evaluate the antilisterial effect of the NSAID Dc with special emphasis on the immunological mechanism of action of the drug.

Berberine in toxin-induced experimental cholera.

1. Oral administration of berberine to infant rabbits 18-24 h before the intraintestinal administration of choleragenic toxins, arrests diarrhoea or significantly prolongs the survival time.2. The use of berberine in the treatment of clinical cholera is further justified.3. Berberine is an antidiarrhoeal drug and the host tissues play a major part in the control of diarrhoeal symptoms.

A study on the antifertility action of VIDR-2GD: a constituent isolated from the seeds of Ensete superbum, Cheesm, Musaceae (Banakadali).

PIP: The antifertility effect of VIDR-2GD, a substance isolated from the seeds of the Musaceae Banakadali, was studied in rabbits, mice, rats, hamsters, and guinea pigs. In mice and rats, pregnancy was inhibited if the drug was given during the preimplantation period single doses of the drug within 3 days after mating inhibited pregnancy. In rabbits, pregnancy was prevented in 50-60% of the animals. The uteri of all the animals receiving the drug were congested and enlarged. No implantation sites were found. Rabbit endometrium showed hyperplasial cells. Uterine stimulation was noted in ovariectomized rats treated with VIDR-2GD. There was no antagonism to estradiol and only a weak antigonadotropic activity shown.^ieng