BMC Pharmacology

BACKGROUND: The emergence of drug resistant tuberculosis poses a serious concern globally and researchers are in rigorous search for new drugs to fight against these dreadful bacteria. Recently, the bacterial GlmU protein, involved in peptidoglycan, lipopolysaccharide and techoic acid synthesis, has been identified as an important drug target. A unique C-terminal disordered tail, essential for survival and the absence of gene in host makes GlmU a suitable target for inhibitor design. RESULTS: This study describes the models developed for predicting inhibitory activity (IC50) of chemical compounds against GlmU protein using QSAR and docking techniques...

BACKGROUND: The serotonin 5-HT2C receptor (5-HT2CR) is expressed in amygdala, a region involved in anxiety and fear responses and implicated in the pathogenesis of several psychiatric disorders such as acute anxiety and post traumatic stress disorder. In humans and in rodent models, there is evidence of both anxiogenic and anxiolytic actions of 5-HT2C ligands. In this study, we determined the responsiveness of 5-HT2CR in serotonin transporter (SERT) knockout (-/-) mice, a model characterized by increased anxiety-like and stress-responsive behaviors...

BACKGROUND: Interferon (IFN) alpha conjugation to polyethylene glycol (PEG) results in a better pharmacokinetic profile and efficacy. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety properties of a new, locally developed, 40-kDa PEG-IFN alpha-2b preparation with a reference, commercially available PEG-IFN alpha-2a in healthy male volunteers. METHODS: A randomized, crossover, double-blind study with a 3-weeks washout period, was done...

BACKGROUND: Sunitinib, a tyrosine kinase inhibitor to treat GIST and mRCC may interact with paracetamol as both undergo P450 mediated biotransformation and P-glycoprotein transport. This study evaluates the effects of sunitinib-paracetamol coadministration on liver and renal function biomarkers and liver, kidney, brain, heart and spleen histopathology. ICR male mice (n = 6 per group/dose) were administered saline (group-A) or paracetamol 500 mg/kg IP (group-B), or sunitinib at 25, 50, 80, 100, 140 mg/kg PO (group-C) or coadministered sunitinib at 25, 50, 80, 100, 140 mg/kg PO and paracetamol IP at fixed dose 500 mg/kg (group-D)...

BACKGROUND: Carbon tetra chloride (CCl4), an industrial solvent, is a hepatotoxic agent and it is the well established animal model for free radical-induced liver injury. The present investigation was carried out to establish the protective effect of natansnin, a novel dibenzoyl glycoside from Salvinia natans against CCl4 induced oxidative stress and cellular degeneration in rat liver. RESULTS: CCl4 significantly increased the levels of lipid peroxides, oxidized glutathione and decreased the levels of reduced glutathione, SOD and CAT...

BACKGROUND: ATP-binding cassette (ABC) transporters protect cells against unrelated (toxic) substances by pumping them across cell membranes. Earlier we showed that many ABC transporters are highly expressed in hematopoietic stem cells (HSCs) compared to more committed progenitor cells. The ABC transporter expression signature may guarantee lifelong protection of HSCs but may also preserve stem cell integrity by extrusion of agents that trigger their differentiation. Here we have studied whether non-hematopoietic stem cells (non-HSCs) exhibit a similar ABC transporter expression signature as HSCs...

BACKGROUND: Although agmatine therapy in a mouse model of transient focal cerebral ischemia is highly protective against neurological injury, the mechanisms underlying the protective effects of agmatine are not fully elucidated. This study aimed to investigate the effects of agmatine on brain apoptosis, astrogliosis and edema in the rats with transient cerebral ischemia. METHODS: Following surgical induction of middle cerebral artery occlusion (MCAO) for 90 min, agmatine (100 mg/kg, i...

BACKGROUND: Infarct-induced left ventricular (LV) remodeling is a deleterious consequence after acute myocardial infarction (MI) which may further advance to congestive heart failure. Therefore, new therapeutic strategies to attenuate the effects of LV remodeling are urgently needed. Salvianolic acid B (SalB) from Salviae mitiorrhizae, which has been widely used in China for the treatment of cardiovascular diseases, is a potential candidate for therapeutic intervention of LV remodeling targeting matrix metalloproteinase-9 (MMP-9)...

BACKGROUND: Long-term amphetamine and methamphetamine dependence has been linked to cerebral blood perfusion, metabolic, and white matter abnormalities. Several studies have linked methamphetamine abuse to cortical grey matter reduction, though with divergent findings. Few publications investigate unmethylated amphetamine's potential effects on cortical grey matter. This work investigated if amphetamine dependent patients showed reduced cortical grey matter thickness. Subjects were 40 amphetamine dependent subjects and 40 healthy controls...

BACKGROUND: Benzylisoquinoline is the structural backbone of many alkaloids with a wide variety of structures including papaverine, noscapine, codeine, morphine, apomorphine, berberine, protopine and tubocurarine. Many benzylisoquinoline alkaloids have been reported to show therapeutic properties and to act as novel medicines. Thus it is important to collect and compile benzylisoquinoline alkaloids in order to explore their usage in medicine. DESCRIPTION: We extract information about benzylisoquinoline alkaloids from various sources like PubChem, KEGG, KNApSAcK and manual curation from literature...

BACKGROUND: The traditional emphasis on developing high specificity pharmaceuticals ("magic bullets") for the treatment of Neurological and Psychiatric disorders is being challenged by emerging pathophysiology concepts that view disease states as abnormal interactions within complex networks of molecular and cellular components. So-called network pharmacology focuses on modifying the behavior of entire systems rather than individual components, a therapeutic strategy that would ideally employ single pharmacological agents capable of interacting with multiple targets ("magic shotguns")...

BACKGROUND: Pramipexole exists as two isomers. The S(-) enantiomer is a potent D3/D2 receptor agonist and is extensively used in the management of PD. In contrast, the R(+) enantiomer is virtually devoid of any of the DA agonist effects. Very limited studies are available to characterize the pharmacological spectrum of the R(+) enantiomer of pramipexole. RESULTS: Using differentiated SH-SY5Y neuroblastoma cells as an experimental model, here we show that S(-) and R(+) pramipexole are endowed with equipotent efficacy in preventing cell death induced by H2O2 and inhibiting mitochondrial reactive oxygen species generation...

No abstract text is available yet for this article.

BACKGROUND: Cannabinoid 1 (CB1) receptor antagonists exhibit pharmacological properties favorable for the treatment of obesity and other related metabolic disorders. CE-178253 (1-[7-(2-Chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a]-[1,3,5]triazin-4-yl]-3-ethylaminoazetidine-3-carboxylic acid hydrochloride) is a recently discovered selective centrally-acting CB1 receptor antagonist. Despite a large body of knowledge on cannabinoid receptor antagonists little data exist on the quantitative pharmacology of this therapeutic class of drugs...

BACKGROUND: Different isoforms of Cytochrome P450 (CYP) metabolized different types of substrates (or drugs molecule) and make them soluble during biotransformation. Therefore, fate of any drug molecule depends on how they are treated or metabolized by CYP isoform. There is a need to develop models for predicting substrate specificity of major isoforms of P450, in order to understand whether a given drug will be metabolized or not. This paper describes an in-silico method for predicting the metabolizing capability of major isoforms (e...

BACKGROUND: We use silkworms to evaluate therapeutic effects of drug candidates. Our previous reports have revealed that there are common mechanisms of pharmacokinetics of chemicals in silkworms and mammals. In this report, we attempt to establish a method by using silkworms to identify chemicals from plant extracts which are absorbed from intestine and also stably exist in body fluids. RESULTS: Three compounds were detected in the silkworm hemolymph by HPLC analysis after midgut injection of acetone extracts of seihi, an herbal medicine obtained from orange peel...

BACKGROUND: It is long known within the mathematical literature that the coefficient of determination R(2) is an inadequate measure for the goodness of fit in nonlinear models. Nevertheless, it is still frequently used within pharmacological and biochemical literature for the analysis and interpretation of nonlinear fitting to data. RESULTS: The intensive simulation approach undermines previous observations and emphasizes the extremely low performance of R(2) as a basis for model validity and performance when applied to pharmacological/biochemical nonlinear data...

BACKGROUND: Pterodon pubescens Benth seeds are commercially available in the Brazilian medicinal plant street market. The crude alcoholic extracts of this plant are used in folk medicine as anti-inflammatory, analgesic, and anti-rheumatic preparations. The aim of this study was to evaluate the contribution of geranylgeraniol (C1) and 6alpha, 7beta-dihydroxyvouacapan-17beta-oate methyl ester (C2) isolated from Pterodon pubescens Benth. to the antinociceptive activity of the crude extract...

BACKGROUND: Wnt signaling affects fundamental development pathways by regulating cell proliferation and differentiation. Aberrant activation of Wnt/beta-catenin signaling promotes the development of several cancers and is an attractive target for chemopreventive and chemotherapeutic agents. RESULTS: In order to identify the novel antagonists for the Wnt/beta-catenin pathway, we employed a cell-based Wnt reporter system (TOPflash) to screen a library of 960 known drugs...

No abstract text is available yet for this article.