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    207 results match your criteria BMC Pharmacology [Journal]

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    Novel olanzapine analogues presenting a reduced H1 receptor affinity and retained 5HT2A/D2 binding affinity ratio.
    BMC Pharmacol 2012 Jun 22;12. Epub 2012 Jun 22.
    Center for Translational Neurosciences, Illawarra Health and Medical Research Institute, School of Health Sciences, The University of Wollongong, Wollongong, NSW, Australia.
    Background: Olanzapine is an atypical antipsychotic drug with high clinical efficacy, but which can cause severe weight gain and metabolic disorders in treated patients. Blockade of the histamine 1 (H1) receptors is believed to play a crucial role in olanzapine induced weight gain, whereas the therapeutic effects of this drug are mainly attributed to its favourable serotoninergic 2A and dopamine 2 (5HT2A/D2) receptor binding affinity ratios.

    Results: We have synthesized novel olanzapine analogues 8a and 8b together with the already known derivative 8c and we have examined their respective in vitro affinities for the 5HT2A, D2, and H1 receptors. Read More

    Lipid phosphate phosphatase inhibitors locally amplify lysophosphatidic acid LPA1 receptor signalling in rat brain cryosections without affecting global LPA degradation.
    BMC Pharmacol 2012 Jun 11;12. Epub 2012 Jun 11.
    School of Pharmacy, University of Eastern Finland, P,O, Box 1627, 70211, Kuopio, Finland.
    Background: Lysophosphatidic acid (LPA) is a signalling phospholipid with multiple biological functions, mainly mediated through specific G protein-coupled receptors. Aberrant LPA signalling is being increasingly implicated in the pathology of common human diseases, such as arteriosclerosis and cancer. The lifetime of the signalling pool of LPA is controlled by the equilibrium between synthesizing and degradative enzymatic activity. Read More

    The orthosteric agonist 2-chloro-5-hydroxyphenylglycine activates mGluR5 and mGluR1 with similar efficacy and potency.
    BMC Pharmacol 2012 May 29;12. Epub 2012 May 29.
    Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
    Background: The efficacy, potency, and selectivity of the compound 2-Chloro-5-hydroxyphenylglycine (CHPG), a nominally selective agonist for metabotropic glutamate receptor 5 (mGluR5), were examined with select mGluRs by examining their ability to induce modulation of the native voltage dependent ion channels in isolated sympathetic neurons from the rat superior cervical ganglion (SCG). SCG neurons offer a null mGluR-background in which specific mGluR subtypes can be made to express via intranuclear cDNA injection.

    Results: Consistent with previous reports, CHPG strongly activated mGluR5b expressed in SCG neurons with an apparent EC50 around 60 μM. Read More

    Long-acting κ opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in mice and lipophilicity.
    BMC Pharmacol 2012 May 29;12. Epub 2012 May 29.
    McLean Hospital, Belmont, MA & Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
    Background: Nor-BNI, GNTI and JDTic induce κ opioid antagonism that is delayed by hours and can persist for months. Other effects are transient. It has been proposed that these drugs may be slowly absorbed or distributed, and may dissolve in cell membranes, thus slowing elimination and prolonging their effects. Read More

    5-hydroxytryptamine (5-HT) reduces total peripheral resistance during chronic infusion: direct arterial mesenteric relaxation is not involved.
    BMC Pharmacol 2012 May 6;12. Epub 2012 May 6.
    Department of Pharmacology and Toxicology, Michigan State University, East, Lansing, MI 48824-1317, USA.
    Serotonin (5-hydroxytryptamine; 5-HT) delivered over 1 week results in a sustained fall in blood pressure in the sham and deoxycorticosterone acetate (DOCA)-salt rat. We hypothesized 5-HT lowers blood pressure through direct receptor-mediated vascular relaxation. In vivo, 5-HT reduced mean arterial pressure (MAP), increased heart rate, stroke volume, cardiac index, and reduced total peripheral resistance during a 1 week infusion of 5-HT (25 µg/kg/min) in the normotensive Sprague Dawley rat. Read More

    Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors.
    BMC Pharmacol 2012 May 3;12. Epub 2012 May 3.
    Department of Molecular & Cellular Physiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0576, USA.
    Background: Linaclotide has been proposed as a treatment for the same gastrointestinal indications for which lubiprostone has been approved, chronic idiopathic constipation and irritable bowel syndrome with constipation. Stressors damage the epithelial cell barrier and cellular homeostasis leading to loss of these functions. Effects of active linaclotide on repair of barrier and cell function in pig jejunum after ischemia and in T84 cells after treatment with proinflammatory cytokines, interferon-γ and tumor necrosis factor-α were examined. Read More

    Potency, selectivity and prolonged binding of saxagliptin to DPP4: maintenance of DPP4 inhibition by saxagliptin in vitro and ex vivo when compared to a rapidly-dissociating DPP4 inhibitor.
    BMC Pharmacol 2012 Apr 4;12. Epub 2012 Apr 4.
    Departments of Metabolic Diseases - Diabetes, Pennington NJ 08534, USA.
    Background: Dipeptidylpeptidase 4 (DPP4) inhibitors have clinical benefit in patients with type 2 diabetes mellitus by increasing levels of glucose-lowering incretin hormones, such as glucagon-like peptide -1 (GLP-1), a peptide with a short half life that is secreted for approximately 1 hour following a meal. Since drugs with prolonged binding to their target have been shown to maximize pharmacodynamic effects while minimizing drug levels, we developed a time-dependent inhibitor that has a half-life for dissociation from DPP4 close to the duration of the first phase of GLP-1 release.

    Results: Saxagliptin and its active metabolite (5-hydroxysaxagliptin) are potent inhibitors of human DPP4 with prolonged dissociation from its active site (Ki = 1. Read More

    Computational models for in-vitro anti-tubercular activity of molecules based on high-throughput chemical biology screening datasets.
    BMC Pharmacol 2012 Mar 31;12. Epub 2012 Mar 31.
    GN Ramachandran Knowledge Center for Genome Informatics, Institute of Genomics and Integrative Biology (CSIR), New Delhi 110007, India.
    Background: The emergence of Multi-drug resistant tuberculosis in pandemic proportions throughout the world and the paucity of novel therapeutics for tuberculosis have re-iterated the need to accelerate the discovery of novel molecules with anti-tubercular activity. Though high-throughput screens for anti-tubercular activity are available, they are expensive, tedious and time-consuming to be performed on large scales. Thus, there remains an unmet need to prioritize the molecules that are taken up for biological screens to save on cost and time. Read More

    The effect of formulation vehicles on the in vitro percutaneous permeation of ibuprofen.
    BMC Pharmacol 2011 Dec 14;11:12. Epub 2011 Dec 14.
    Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Buenteweg 17, 30559 Hannover, Germany.
    Background: The transdermal application of substances represents an elegant approach to overcome side effects related to injections or oral treatment. Due to benefits like a constant plasma level, no pain during application and a simple therapeutic regime, the optimization of formulations for transdermal drug delivery has gained interest in the last decades. Ibuprofen is a non-steroidal anti-inflammatory compound which is nowadays often used transdermally. Read More

    Polyamidoamine (PAMAM) dendrimer conjugate specifically activates the A3 adenosine receptor to improve post-ischemic/reperfusion function in isolated mouse hearts.
    BMC Pharmacol 2011 Oct 31;11:11. Epub 2011 Oct 31.
    Department of Pharmacology/Toxicology and the Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
    Background: When stimulated by small molecular agonists, the A3 adenosine receptor (AR) mediates cardioprotective effects without inducing detrimental hemodynamic side effects. We have examined pharmacologically the protective properties of a multivalent dendrimeric conjugate of a nucleoside as a selective multivalent agonist for the mouse A3AR.

    Results: A PAMAM dendrimer fully substituted by click chemistry on its peripheral groups with 64 moieties of a nucleoside agonist was shown to be potent and selective in binding to the mouse A3AR and effective in cardioprotection in an isolated mouse heart model of ischemia/reperfusion (I/R) injury. Read More

    Protection of protease-activated receptor 2 mediated vasodilatation against angiotensin II-induced vascular dysfunction in mice.
    BMC Pharmacol 2011 Sep 28;11:10. Epub 2011 Sep 28.
    Memorial University, St, John's, Newfoundland and Labrador, Canada.
    Background: Under conditions of cardiovascular dysfunction, protease-activated receptor 2 (PAR2) agonists maintain vasodilatation activity, which has been attributed to increased cyclooxygenase-2, nitric oxide synthase and calcium-activated potassium channel (SK3.1) activities. Protease-activated receptor 2 agonist mediated vasodilatation is unknown under conditions of dysfunction caused by angiotensin II. Read More

    Towards the development of novel Trypanosoma brucei RNA editing ligase 1 inhibitors.
    BMC Pharmacol 2011 Aug 30;11. Epub 2011 Aug 30.
    Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, California 92093-0365, USA.
    Background: Trypanosoma brucei (T. brucei) is an infectious agent for which drug development has been largely neglected. We here use a recently developed computer program called AutoGrow to add interacting molecular fragments to S5, a known inhibitor of the validated T. Read More

    Dexamethasone restrains ongoing expression of interleukin-23p19 in peripheral blood-derived human macrophages.
    BMC Pharmacol 2011 Jul 26;11. Epub 2011 Jul 26.
    Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Via A, Saffi 2, 61029 Urbino, PU, Italy.
    Background: Since its recent discovery, interleukin-23 has been shown to be involved in the pathogenesis of autoimmune diseases favoring the development of a T cell subset referred to as T helper 17. Glucocorticoids are widely employed in inflammatory and autoimmune diseases as they inhibit pro-inflammatory signaling and prevent production of inflammation mediators. Very limited information is available about the efficacy of synthetic glucocorticoids in containing the expression of interleukin-23 under cell activation. Read More

    Enhanced sensitivity to cisplatin and gemcitabine in Brca1-deficient murine mammary epithelial cells.
    BMC Pharmacol 2011 Jul 19;11. Epub 2011 Jul 19.
    Department of Medicine, Division of Oncology, Stanford University School of Medicine, Center for Clinical Sciences Research, Stanford, CA 94305, USA.
    Background: Breast cancers due to germline mutations or altered expression of the BRCA1 gene associate with an aggressive clinical course and frequently exhibit a "triple-negative" phenotype, i.e. lack of expression of the estrogen and progesterone hormone receptors and lack of overexpression of the HER2/NEU oncogene, thereby rendering them relatively insensitive to hormonal manipulation and targeted HER2 therapy, respectively. Read More

    Differential effects of TRPV1 receptor ligands against nicotine-induced depression-like behaviors.
    BMC Pharmacol 2011 Jul 18;11. Epub 2011 Jul 18.
    Department of Legal Medicine, Kyoto University, Kyoto 606-8501, Japan.
    Background: The contributions of brain cannabinoid (CB) receptors, typically CB1 (CB type 1) receptors, to the behavioral effects of nicotine (NC) have been reported to involve brain transient receptor potential vanilloid 1 (TRPV1) receptors, and the activation of candidate endogenous TRPV1 ligands is expected to be therapeutically effective. In the present study, the effects of TRPV1 ligands with or without affinity for CB1 receptors were examined on NC-induced depression-like behavioral alterations in a mouse model in order to elucidate the "antidepressant-like" contributions of TRPV1 receptors against the NC-induced "depression" observed in various types of tobacco abuse.

    Results: Repeated subcutaneous NC treatments (NC group: 0. Read More

    A web server for predicting inhibitors against bacterial target GlmU protein.
    BMC Pharmacol 2011 Jul 6;11. Epub 2011 Jul 6.
    Institute of Microbial Technology, Chandigarh, India.
    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. Read More

    Synthesis of 86 species of 1,5-diaryl-3-oxo-1,4-pentadienes analogs of curcumin can yield a good lead in vivo.
    BMC Pharmacol 2011 May 28;11. Epub 2011 May 28.
    Dept. Clinical Oncology, Institute of Development, Aging, and Cancer, Tohoku University, Seiryo-cho 4-1, Aoba-ku, Sendai, Japan.
    Background: Curcumin is known to possess many anti-tumor properties such as inhibition of tumor growth and induction of apotosis. However, limited bioavailability of curcumin prevents its clinical application. A synthesized curcumin analog, 1,5-diaryl-3-oxo-1,4-pentadiene such as GO-Y030, has the improved anti-tumor potential in vitro as well as in mouse model of colorectal carcinogenesis. Read More

    Altered 5-HT2C receptor agonist-induced responses and 5-HT2C receptor RNA editing in the amygdala of serotonin transporter knockout mice.
    BMC Pharmacol 2011 Apr 7;11. Epub 2011 Apr 7.
    Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
    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. Read More

    Effects of rasagiline, its metabolite aminoindan and selegiline on glutamate receptor mediated signalling in the rat hippocampus slice in vitro.
    BMC Pharmacol 2011 Feb 21;11. Epub 2011 Feb 21.
    Justus Liebig University Giessen, c/o NeuroCode AG, Sportparkstr, 9, D 35578 Wetzlar, Germany.
    Background: Rasagiline, a new drug developed to treat Parkinson's disease, is known to inhibit monoamine oxidase B. However, its metabolite R-(-)-aminoindan does not show this kind of activity. The present series of in vitro experiments using the rat hippocampal slice preparation deals with effects of both compounds on the pyramidal cell response after electric stimulation of the Schaffer Collaterals in comparison to selegiline, another MAO B inhibitor. Read More

    The boron-oxygen core of borinate esters is responsible for the store-operated calcium entry potentiation ability.
    BMC Pharmacol 2011 Jan 26;11. Epub 2011 Jan 26.
    INSERM UMR-S 940, Institut Universitaire d'Hématologie - Université Denis Diderot Paris 7, Hôpital Saint Louis, Paris, France.
    Background: Store-Operated Calcium Entry (SOCE) is the major Ca2+ ion entry pathway in lymphocytes and is responsible of a severe combined immunodeficiency (SCID) when deficient. It has recently been observed or highlighted in other cell types such as myoblasts and neurons, suggesting a wider physiological role of this pathway. Whereas Orai1 protein is considered to be the channel allowing the SOCE in T cells, it is hypothesized that other proteins like TRPC could associate with Orai1 to form SOCE with different pharmacology and kinetics in other cell types. Read More

    Pharmacokinetic and pharmacodynamic comparison of two "pegylated" interferon alpha-2 formulations in healthy male volunteers: a randomized, crossover, double-blind study.
    BMC Pharmacol 2010 Nov 23;10:15. Epub 2010 Nov 23.
    Clinical Trials Division, Center for Biological Research, Havana, Cuba.
    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. Read More

    Histopathology and biochemistry analysis of the interaction between sunitinib and paracetamol in mice.
    BMC Pharmacol 2010 Oct 15;10:14. Epub 2010 Oct 15.
    Department of Human Biology, School of Medicine, International Medical University, Jalan 19/155B, Bukit Jalil, 57000 Kuala Lumpur, Malaysia.
    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). Read More

    Protective efficacy of natansnin, a dibenzoyl glycoside from Salvinia natans against CCl4 induced oxidative stress and cellular degeneration in rat liver.
    BMC Pharmacol 2010 Oct 12;10:13. Epub 2010 Oct 12.
    Department of Genetics, Osmania University, Hyderabad, India.
    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. Read More

    Hematopoietic stem cells exhibit a specific ABC transporter gene expression profile clearly distinct from other stem cells.
    BMC Pharmacol 2010 Sep 13;10:12. Epub 2010 Sep 13.
    Department of Laboratory Medicine, Laboratory of Hematology, Radboud University Nijmegen Medical Centre/Nijmegen Centre for Molecular Life Sciences, Geert Grooteplein 8, 6525GA Nijmegen, The Netherlands.
    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. Read More

    Beneficial effect of agmatine on brain apoptosis, astrogliosis, and edema after rat transient cerebral ischemia.
    BMC Pharmacol 2010 Sep 6;10:11. Epub 2010 Sep 6.
    Department of Biotechnology, Southern Taiwan University, Tainan 710, Taiwan.
    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. Read More

    Salvianolic acid B functioned as a competitive inhibitor of matrix metalloproteinase-9 and efficiently prevented cardiac remodeling.
    BMC Pharmacol 2010 Aug 25;10:10. Epub 2010 Aug 25.
    Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
    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). Read More

    Quantitative in vitro and in vivo pharmacological profile of CE-178253, a potent and selective cannabinoid type 1 (CB1) receptor antagonist.
    BMC Pharmacol 2010 Aug 16;10. Epub 2010 Aug 16.
    Department of Cardiovascular, Metabolic and Endocrine Diseases, Pfizer Global Research and Development, Groton, CT 06340, USA.
    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. Read More

    Prediction of cytochrome P450 isoform responsible for metabolizing a drug molecule.
    BMC Pharmacol 2010 Jul 16;10. Epub 2010 Jul 16.
    Bioinformatics Centre, Institute of Microbial Technology, Chandigarh, India.
    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. Read More

    Use of silkworms for identification of drug candidates having appropriate pharmacokinetics from plant sources.
    BMC Pharmacol 2010 Jun 11;10. Epub 2010 Jun 11.
    Department of Microbiology, Faculty of Pharmaceutical Sciences, Graduate of the University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan.
    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. Read More

    An evaluation of R2 as an inadequate measure for nonlinear models in pharmacological and biochemical research: a Monte Carlo approach.
    BMC Pharmacol 2010 Jun 7;10. Epub 2010 Jun 7.
    Department of Andrology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
    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. Read More

    Amphetamine dependence and co-morbid alcohol abuse: associations to brain cortical thickness.
    BMC Pharmacol 2010 May 20;10. Epub 2010 May 20.
    Department of Psychiatry, University of Oslo, Norway.
    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. Read More

    BIAdb: a curated database of benzylisoquinoline alkaloids.
    BMC Pharmacol 2010 Mar 5;10. Epub 2010 Mar 5.
    Bioinformatics Centre, Institute of Microbial Technology (CSIR), Chandigarh, India.
    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. Read More

    Targeting ligand-gated ion channels in neurology and psychiatry: is pharmacological promiscuity an obstacle or an opportunity?
    BMC Pharmacol 2010 Mar 2;10. Epub 2010 Mar 2.
    Neurology Department, Sleep Division, Massachusetts General Hospital, Boston, MA, USA.
    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"). For this approach to be successful, however, a framework for understanding pharmacological "promiscuity"--the ability of individual agents to modulate multiple molecular targets--is needed. Read More

    Mitochondria-targeted antioxidant effects of S(-) and R(+) pramipexole.
    BMC Pharmacol 2010 Feb 5;10. Epub 2010 Feb 5.
    Department of Biomedical Sciences and Biotechnologies and National Institute of Neuroscience, University of Brescia, Brescia, Italy.
    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. Read More

    Antinociceptive effect of geranylgeraniol and 6alpha,7beta-dihydroxyvouacapan-17beta-oate methyl ester isolated from Pterodon pubescens Benth.
    BMC Pharmacol 2010 Jan 7;10. Epub 2010 Jan 7.
    CPQBA- State University of Campinas, PO Box 6171, 13083-970 Campinas, SP, Brazil.
    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. Read More

    Divergence of allosteric effects of rapacuronium on binding and function of muscarinic receptors.
    BMC Pharmacol 2009 Dec 28;9:15. Epub 2009 Dec 28.
    Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
    Background: Many neuromuscular blockers act as negative allosteric modulators of muscarinic acetylcholine receptors by decreasing affinity and potency of acetylcholine. The neuromuscular blocker rapacuronium has been shown to have facilitatory effects at muscarinic receptors leading to bronchospasm. We examined the influence of rapacuronium on acetylcholine (ACh) binding to and activation of individual subtypes of muscarinic receptors expressed in Chinese hamster ovary cells to determine its receptor selectivity. Read More

    Differential regulation of muscarinic M1 receptors by orthosteric and allosteric ligands.
    BMC Pharmacol 2009 Dec 2;9:14. Epub 2009 Dec 2.
    ACADIA Pharmaceuticals Inc, 3911 Sorrento Valley Blvd, San Diego, CA 92121, USA.
    Background: Activation of muscarinic M1 receptors is mediated via interaction of orthosteric agonists with the acetylcholine binding site or via interaction of allosteric agonists with different site(s) on the receptor. The focus of the present study was to determine if M1 receptors activated by allosteric agonists undergo the same regulatory fate as M1 receptors activated by orthosteric agonists.

    Results: The orthosteric agonists carbachol, oxotremorine-M and pilocarpine were compared to the allosteric agonists AC-42, AC-260584, N-desmethylclozapine and xanomeline. Read More

    Spiperone enhances intracellular calcium level and inhibits the Wnt signaling pathway.
    BMC Pharmacol 2009 Nov 30;9:13. Epub 2009 Nov 30.
    Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA.
    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. Read More

    An efficient drug delivery vehicle for botulism countermeasure.
    BMC Pharmacol 2009 Oct 27;9:12. Epub 2009 Oct 27.
    Division of Experimental Therapeutic, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
    Background: Botulinum neurotoxin (BoNT) is the most potent poison known to mankind. Currently no antidote is available to rescue poisoned synapses. An effective medical countermeasure strategy would require developing a drug that could rescue poisoned neuromuscular synapses and include its efficient delivery specifically to poisoned presynaptic nerve terminals. Read More

    Evaluation of molecular descriptors for antitumor drugs with respect to noncovalent binding to DNA and antiproliferative activity.
    BMC Pharmacol 2009 Sep 16;9:11. Epub 2009 Sep 16.
    Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, Baldiri Reixac, 10, E-08028 Barcelona, Spain.
    Background: Small molecules that bind reversibly to DNA are among the antitumor drugs currently used in chemotherapy. In the pursuit of a more rational approach to cancer chemotherapy based upon these molecules, it is necessary to exploit the interdependency between DNA-binding affinity, sequence selectivity and cytotoxicity. For drugs binding noncovalently to DNA, it is worth exploring whether molecular descriptors, such as their molecular weight or the number of potential hydrogen acceptors/donors, can account for their DNA-binding affinity and cytotoxicity. Read More

    Psychotropic drugs up-regulate the expression of cholesterol transport proteins including ApoE in cultured human CNS- and liver cells.
    BMC Pharmacol 2009 Aug 29;9:10. Epub 2009 Aug 29.
    Department of Clinical Medicine, University of Bergen, Dr Einar Martens' Research Group for Biological Psychiatry and Bergen Mental Health Research Center, Norway.
    Background: Disturbances in lipid homeostasis and myelination have been proposed in the pathophysiology of schizophrenia and bipolar disorder. We have previously shown that several antipsychotic and antidepressant drugs increase lipid biosynthesis through activation of the Sterol Regulatory Element-Binding Protein (SREBP) transcription factors, which control the expression of numerous genes involved in fatty acid and cholesterol biosynthesis. The aim of the present proof-of-principle study was to investigate whether such drugs also affect lipid transport and export pathways in cultured human CNS and liver cells. Read More

    A covalent peptide inhibitor of RGS4 identified in a focused one-bead, one compound library screen.
    BMC Pharmacol 2009 May 22;9. Epub 2009 May 22.
    Department of Pharmacology, University of Michigan,1301 MSRB III SPC 5632, 1150 W, Medical Center Dr, Ann Arbor, MI 48109, USA.
    Background: Regulators of G protein signaling (RGSs) accelerate GTP hydrolysis by Galpha subunits and profoundly inhibit signaling by G protein-coupled receptors (GPCRs). The distinct expression patterns and pathophysiologic regulation of RGS proteins suggest that inhibitors may have therapeutic potential. We recently described a focused one-bead, one-compound (OBOC) library screen to identify peptide inhibitors of RGS4. Read More

    Rapamycin weekly maintenance dosing and the potential efficacy of combination sorafenib plus rapamycin but not atorvastatin or doxycycline in tuberous sclerosis preclinical models.
    BMC Pharmacol 2009 Apr 15;9. Epub 2009 Apr 15.
    Translational Medicine Division, Department of Medicine, Brigham & Women's Hospital, Karp Building, Boston, MA, USA.
    Background: Tuberous sclerosis complex (TSC) is an autosomal dominant tumor suppressor syndrome, characterized by hamartomatous growths in the brain, skin, kidneys, lungs, and heart, which lead to significant morbidity. TSC is caused by mutations in the TSC1 or TSC2 genes, whose products, hamartin and tuberin, form a tumor suppressor complex that regulates the PI3K/Akt/mTOR pathway. Early clinical trials show that TSC-related kidney tumors (angiomyolipomas) regress when treated with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin (also known as sirolimus). Read More

    N-acetylcysteine amide decreases oxidative stress but not cell death induced by doxorubicin in H9c2 cardiomyocytes.
    BMC Pharmacol 2009 Apr 15;9. Epub 2009 Apr 15.
    Department of Chemistry, Missouri University of Science and Technology, 400 W. 11st Street, 142 Schrenk Hall, Rolla, MO 65409, USA.
    Background: While doxorubicin (DOX) is widely used in cancer chemotherapy, long-term severe cardiotoxicity limits its use. This is the first report of the chemoprotective efficacy of a relatively new thiol antioxidant, N-acetylcysteine amide (NACA), on DOX-induced cell death in cardiomyocytes. We hypothesized that NACA would protect H9c2 cardiomyocytes from DOX-induced toxicity by reducing oxidative stress. Read More

    Haloperidol changes mRNA expression of a QKI splice variant in human astrocytoma cells.
    BMC Pharmacol 2009 Mar 31;9. Epub 2009 Mar 31.
    Department of Development and Genetics, Uppsala University, Sweden.
    Background: The quaking homolog, KH domain RNA binding (mouse) (QKI) is a candidate gene for schizophrenia. Disturbed QKI mRNA expression is observed in the prefrontal cortex of patients, and some of these changes correlate to treatment with antipsychotic drugs.To test if low doses of antipsychotic drugs can modify QKI mRNA expression, human astrocytoma (U343) and oligodendroglioma (HOG) cell lines were treated with five different antipsychotic drugs including Haloperidol, Aripiprazole, Clozapine, Olanzapine and Risperidone. Read More

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