http://precedings.nature.com/tags/Pharmacology Recently posted documents tagged with 'Pharmacology' Nature Publishing Group en Nature Precedings http://precedings.nature.com/images/header_logo.gif http://precedings.nature.com http://dx.doi.org/10.1038/npre.2009.3230.1 The International Union of Basic and Clinical Pharmacology database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 non-sensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of about a third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. Individual gene pages provide a comprehensive description of the genes and their functions, with information on protein structure, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). The phenotypes resulting from altered gene expression (e.g. in genetically altered animals) and genetic mutations are described. Links are provided to bioinformatics resources such as NCBI RefSeq, OMIM, PubChem, human, rat and mouse genome databases. Recent developments include the addition of ligand-centered pages summarising information about unique ligand molecules in IUPHAR-DB. IUPHAR-DB represents a novel approach to biocuration because most data are provided through manual curation of published literature by a network of over 60 expert subcommittees coordinated by NC-IUPHAR. Data are referenced to the primary literature and linked to PubMed. The data are checked to ensure accuracy and consistency by the curators, added to the production server using custom-built submission tools and peer-reviewed by NC-IUPHAR, before being transferred to the public database. Data are reviewed and updated regularly (at least biennially). Other website features include comprehensive database search tools, online and downloadable gene lists and links to recent publications of interest to the field, such as reports on receptor-ligand pairings. The database is freely available at http://www.iuphar-db.org. Curators can be reached at curators [at] iuphar-db.org. We thank British Pharmacological Society, UNESCO (through the ICSU Grants Programme), Incyte, GlaxoSmithKline, Novartis, Servier and Wyeth for their support. http://dx.doi.org/10.1038/npre.2009.3230.1 Thu, 07 May 2009 18:58:20 UTC IUPHAR-DB: An Expert-Curated, Peer-Reviewed Database of Receptors and Ion Channels doi:10.1038/npre.2009.3230.1 2009-05-07 Joanna L. Sharman Nature Precedings 2009-05-07T18:58:20Z Poster Pharmacology Bioinformatics http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/2319/version/1 Cocaine inhibits high-affinity neurotransmitter uptake at the presynaptic nerve terminals to increase synaptic levels of dopamine, norepinephrine and serotonin1. This increase of synaptic dopamine may cause neurotoxicity2,3. At least two different mechanisms have been proposed for the development of dopamine-related neurotoxicity: 1) dopamine produces a free radical that may induce cell toxicity2,3 and 2) dopamine reduces glutamate transport at its presynaptic sites to increase synaptic levels of this amino acid4 and augments glutamate transmission by activating dopamine D1 receptors in different areas of the brain5-7. Increase in glutamatergic transmission mediated by the activation on N-methyl dextro-aspartate (NMDA) receptors has been shown to cause excitotoxicity and neuro-degeneration8. Others and we have reported protection against different psychotropic drug-induced neurotoxicity that may be achieved by prior or simultaneous administration of various pharmacological agents. For example, repeated treatment of rats with haloperidol induced neuronal damage that is ameliorated by prior administration of either GM1 ganglioside9 or the endogenous amino acid, taurine10. Similarly, chronic gestational cocaine exposure causes neurotoxicity that could be prevented by co-administration of clozapine11. To our knowledge, there is no information if chronic cocaine would enhance release of endogenous protective agents that may oppose the over activation of glutamatergic system. Here we show that repeated cocaine treatment increased synaptic levels of the neuroprotective amino acid taurine that opposes the excessive excitatory actions of the glutamatergic system in the rat brain. Thus, mammalian brain has an auto-protective mechanism to counter excitotoxicity and taurine or its synthetic derivative may be useful in the management and treatment of cocaine addiction and its neurotoxic effect. http://precedings.nature.com/documents/2319/version/1 Wed, 24 Sep 2008 10:21:20 UTC Chronic cocaine enhances release of neuroprotective amino acid taurine: a microdialysis study hdl:10101/npre.2008.2319.1 2008-09-24 Mervan Agovic Nature Precedings 2008-09-24T10:21:20Z Manuscript Neuroscience Pharmacology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/2164/version/1 We report the use of axonal transport to achieve intraneural drug delivery. We constructed a novel tripartite complex of an axonal transport facilitator conjugated to a linker molecule bearing up to a hundred reversibly attached drug molecules. The complex efficiently enters nerve terminals after intramuscular or intradermal administration and travels within axonal processes to neuron cell bodies. The tripartite agent provided 100-fold amplification of saturable neural uptake events, delivering multiple drug molecules per complex. In vivo, analgesic drug delivery to systemic and to non-targeted neural tissues was greatly reduced compared to existing routes of administration, thus exemplifying the possibility of specific nerve root targeting and effectively increasing the potency of the candidate drug gabapentin 300-fold relative to oral administration. http://precedings.nature.com/documents/2164/version/1 Thu, 07 Aug 2008 12:00:47 UTC Successful use of axonal transport for drug delivery by synthetic molecular vehicles hdl:10101/npre.2008.2164.1 2008-08-07 Aaron G. Filler Nature Precedings 2008-08-07T12:00:47Z Manuscript Biotechnology Chemistry Molecular Cell Biology Neuroscience Pharmacology http://creativecommons.org/licenses/by/3.0/ http://precedings.nature.com/documents/1439/version/1 The sensory contact model allows forming different psycho-pathological states (anxious depression, catalepsy, social withdrawal, pathological aggression, cognition disturbances, anhedonia, addictive states etc.) produced by repeated agonistic interactions in male mice and investigating the therapeutic and preventive properties of any drug as well as its efficiency under simulated clinical conditions. This approach can be useful for a better understanding of the drugs’ action in different stages of disease development in individuals. It is suggested that this behavioral approach and pharmacological designs may be applied for the screening of novel psychotropic drugs. http://precedings.nature.com/documents/1439/version/1 Wed, 19 Dec 2007 14:51:26 UTC Application of the Sensory Contact Model for Pharmacological Studies under Simulated Clinical Conditions hdl:10101/npre.2007.1439.1 2007-12-19 Natalia N. Kudryavtseva Nature Precedings 2007-12-19T14:51:26Z Manuscript Neuroscience Pharmacology http://creativecommons.org/licenses/by/3.0/ http://dx.doi.org/10.1038/npre.2007.1239.1 This talk presents a method that predicts adverse side effects for molecules based on the chemical structure only. Also, targets for the compounds are predicted. Therefore it becomes possible to link a certain side effect to the interaction with a certain target through molecular space. Examples are given in the talk. http://dx.doi.org/10.1038/npre.2007.1239.1 Tue, 23 Oct 2007 15:06:12 UTC Side effect profile prediction – Tackling Big Pharma’s worst nightmare at an early stage doi:10.1038/npre.2007.1239.1 2007-10-23 Josef Scheiber Nature Precedings 2007-10-23T15:06:12Z Presentation Chemistry Pharmacology Bioinformatics http://creativecommons.org/licenses/by/2.5/