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The neurotoxic properties of the amphetamines such as methamphetamine (METH) were originally described about the time of the National Institute on Drug Abuse's organization, in the early 1970s. It required more than 20 years to confirm these neurotoxic properties in humans. Much like Parkinson's disease, multiple high-dose administration of METH somewhat selectively damages the nigrostriatal dopamine (DA) projection of the brain. This effect appears to be related to the intracellular accumulation of cytosolic DA and its ability to oxidize into reactive oxygen species. Both the dopamine plasmalemmal transporter and the vesicular monoamine transporter-2 seem to play critical roles in this neurotoxicity. METH and related analogs such as methylenedioxymethamphetamine (MDMA) can also damage selective CNS serotonin neurons. The mechanism of the serotonergic neurotoxicity is not as well characterized, but also appears to be related to the formation of reactive oxygen species and monoamine transporters. Studies examining the pharmacological and neurotoxicological properties of the amphetamines have helped to elucidate some critical features of monoamine regulations as well as helped to improve our understanding of the processes associated with degenerative disorders such as Parkinson's disease.  相似文献   

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Although the hormone relaxin was discovered 80 years ago, only in the past 5 years have the receptors for relaxin and three other receptors that respond to related peptides been identified with all four receptors being G-protein-coupled receptors. In this review it is suggested that the receptors for relaxin (LGR7) and those for the related peptides insulin-like peptide 3 (LGR8), relaxin-3 (GPCR135), and insulin-like peptide 5 (LGPCR142) be named the relaxin family peptide receptors 1 through 4 (RXFP1-4). RXFP1 and RXFP2 are leucine-rich repeat-containing G-protein-coupled receptors with complex binding characteristics involving both the large ectodomain and the transmembrane loops. RXFP1 activates adenylate cyclase, protein kinase A, protein kinase C, phosphatidylinositol 3-kinase, and extracellular signaling regulated kinase (Erk1/2) and also interacts with nitric oxide signaling. RXFP2 activates adenylate cyclase in recombinant systems, but physiological responses are sensitive to pertussis toxin. RXFP3 and RXFP4 resemble more conventional peptide liganded receptors and both inhibit adenylate cyclase, and in addition RXFP3 activates Erk1/2 signaling. Physiological studies and examination of the phenotypes of transgenic mice have established that relaxin has roles as a reproductive hormone involved in uterine relaxation (some species), reproductive tissue growth, and collagen remodeling but also in the cardiovascular and renal systems and in the brain. The connective tissue remodeling properties of relaxin acting at RXFP1 receptors have potential for the development of agents effective for the treatment of cardiac and renal fibrosis, asthma, and scleroderma and for orthodontic remodelling. Agents acting at RXFP2 receptors may be useful for the treatment of cryptorchidism and infertility, whereas antagonists may be used as contraceptives. The brain distribution of RXFP3 receptors suggests that actions at these receptors have the potential for the development of antianxiety and antiobesity drugs.  相似文献   

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The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full.This compilation of the major pharmacological targets is divided into seven areas of focus: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets.It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.  相似文献   

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Although anesthesia was available to patients when the doors of The Jews Hospital opened in 1855, "professional anesthetists" were not appointed to the staff until 1902. This article traces the history of the anesthesiology staff and department, and documents their accomplishments over the past century.  相似文献   

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This article aims to provide a research update on nitroxide radical compounds for application of anti-oxidative stress therapy. Nitroxide compounds such as 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO) can catalytically react with reactive oxygen species (ROS) and are anticipated as new anti-oxidant therapies for several diseases. However, low-molecular-weight nitroxide compounds pose several problems such as nonspecific dispersion in normal tissues, preferential renal clearance and rapid reduction of the nitroxide radical to the corresponding hydroxylamine. Nitroxide radical compounds are also known to show dose-related antihypertensive action accompanied by reflex tachycardia, increased skin temperature, and seizures. The author has recently designed novel nanoparticles, which possess nitroxide radicals in the core for novel bioimaging and nanotherapy. Nitroxide radical-containing nanoparticles (RNP) shows high safety, long blood circulation, magnetic resonance imaging and ESR imaging sensitive character and efficient therapeutic effects to several diseases such as cerebral and renal ischemia reperfusions, ulcerative colitis and Alzheimer's disease models. RNPs are, thus, promising as new nanotherapeutic materials.  相似文献   

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The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full.Enzymes are one of the seven major pharmacological targets into which the Guide is divided, with the others being G protein-coupled receptors, ligand-gated ion channels, ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets.It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors and Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and the Guide to Receptors and Channels, providing a permanent, citable, point-in-time record that will survive database updates.  相似文献   

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The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full.Transporters are one of the seven major pharmacological targets into which the Guide is divided, with the others being G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets.It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors and Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and the Guide to Receptors and Channels, providing a permanent, citable, point-in-time record that will survive database updates.  相似文献   

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Medical treatment level is related with rise and fall of nation. Medical education is one of the most important education. Pharmacology, as the main subject of medical science, is the bridge of medical and pharmaceutical sciences, as well as the bridge of preclinical and clinical medicine. With the elucidation of pathogenesis of some serious disease, new drug exploitation, research of mechanism of action and reasonable application become more and more important. As a pharmacological teacher, whether we can impart these essence to our students and whether these medical students will use very well in the future what they have learned, are l~oth challenge to battle we are facing with. Through years of teaching work, I have some comprehends about pharmacology teaching. In my opinion, we should try our best to make students grasp basic knowledge firstly because it is the basic requirements to be a qualified physician.  相似文献   

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