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Article ; Online: Biographical Feature: Stephen G. Jenkins, Ph.D., D(ABMM), F(AAM).

McAdam, Alexander J

2019 Volume 57, Issue 5

MeSH term(s)	Awards and Prizes ; Biomedical Research ; Diagnostic Tests, Routine ; History, 20th Century ; History, 21st Century ; Humans ; Leadership ; Microbiology/history
Language	English
Publishing date	2019-04-26
Publishing country	United States
Document type	Biography ; Historical Article ; Journal Article
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/JCM.00299-19
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Article: Barriers to the wider adoption of medicinal

Alexander, Stephen Ph

British journal of pain

2020 Volume 14, Issue 2, Page(s) 122–132

Abstract: ... The use ... ...

Abstract	The use of
Language	English
Publishing date	2020-05-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2670872-3
ISSN	2049-4645 ; 2049-4637
ISSN (online)	2049-4645
ISSN	2049-4637
DOI	10.1177/2049463720922884
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Article: Endocannabinoid hydrolases differentially distribute in platelets and red blood cells and are differentially released by thrombin.

Anajirih, Nuha / O'Sullivan, Saoirse E / Alexander, Stephen Ph

Prostaglandins & other lipid mediators

2022 Volume 164, Page(s) 106692

Abstract: Background: Plasma levels of the major endocannabinoids 2-arachidonoylgycerol (2AG) and anandamide (N-arachidonoylethanolamine, AEA) have been identified to vary independently with particular pathological conditions. The levels of these endocannabinoids ...

Abstract	Background: Plasma levels of the major endocannabinoids 2-arachidonoylgycerol (2AG) and anandamide (N-arachidonoylethanolamine, AEA) have been identified to vary independently with particular pathological conditions. The levels of these endocannabinoids are tightly regulated by two hydrolytic enzymes, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), respectively. Objectives: In this study, we have quantified these enzyme activities in the major blood fractions. Patients/methods: In blood fractions from human volunteers, radiometric assays were used to quantify monoacylglycerol lipase and fatty acid amide hydrolase. Tagging with fluorophosphonate-rhodamine allowed quantification of platelet serine hydrolase activities. Results: Fatty acid amide hydrolase activity was highest in platelets, while MAGL activity was most abundant in erythrocytes. Sampling the blood of donors on two further occasions 15 days apart showed no significant change in platelet FAAH or erythrocyte MAGL activities. Activities were not different when comparing female donors with males. Storage of these blood fractions at - 80 °C was associated with a rapid loss in enzyme activities, which could largely by avoided by storage in liquid nitrogen. Incubation of platelets and erythrocytes in the presence of thrombin lead to release of measurable FAAH, but not MAGL, activity. Tagging of serine hydrolase activities with fluorophosphonate-rhodamine allowed confirmation of MAGL activity in platelet preparations, as well as multiple other enzymes. Conclusions: These investigations suggest a potential role for FAAH in regulation of coagulation, while the role of MAGL in blood requires further investigation.
MeSH term(s)	Female ; Humans ; Male ; Endocannabinoids ; Enzyme Inhibitors ; Erythrocytes ; Monoacylglycerol Lipases ; Serine ; Thrombin/metabolism
Chemical Substances	anandamide (UR5G69TJKH) ; Endocannabinoids ; Enzyme Inhibitors ; Monoacylglycerol Lipases (EC 3.1.1.23) ; Serine (452VLY9402) ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2022-11-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1426962-4
ISSN	2212-196X ; 1098-8823 ; 0090-6980
ISSN (online)	2212-196X
ISSN	1098-8823 ; 0090-6980
DOI	10.1016/j.prostaglandins.2022.106692
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Article: MEA-NAP compares microscale functional connectivity, topology, and network dynamics in organoid or monolayer neuronal cultures.

bioRxiv : the preprint server for biology

2024

Abstract: Microelectrode array (MEA) recordings are commonly used to compare firing and burst rates in neuronal cultures. MEA recordings can also reveal microscale functional connectivity, topology, and network dynamics-patterns seen in brain networks across ... ...

Abstract	Microelectrode array (MEA) recordings are commonly used to compare firing and burst rates in neuronal cultures. MEA recordings can also reveal microscale functional connectivity, topology, and network dynamics-patterns seen in brain networks across spatial scales. Network topology is frequently characterized in neuroimaging with graph theoretical metrics. However, few computational tools exist for analyzing microscale functional brain networks from MEA recordings. Here, we present a MATLAB MEA network analysis pipeline (MEA-NAP) for raw voltage time-series acquired from single- or multi-well MEAs. Applications to 3D human cerebral organoids or 2D human-derived or murine cultures reveal differences in network development, including topology, node cartography, and dimensionality. MEA-NAP incorporates multi-unit template-based spike detection, probabilistic thresholding for determining significant functional connections, and normalization techniques for comparing networks. MEA-NAP can identify network-level effects of pharmacologic perturbation and/or disease-causing mutations and, thus, can provide a translational platform for revealing mechanistic insights and screening new therapeutic approaches.
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.05.578738
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Article ; Online: Endocannabinoid system imbalance in the postmortem prefrontal cortex of subjects with schizophrenia.

Muguruza, Carolina / Morentin, Benito / Meana, J Javier / Alexander, Stephen Ph / Callado, Luis F

Journal of psychopharmacology (Oxford, England)

2019 Volume 33, Issue 9, Page(s) 1132–1140

Abstract: Background: The endocannabinoid system - comprising cannabinoid receptors, endocannabinoid ligands and their synthesis and inactivation enzymes - has been widely implicated in the pathophysiology of schizophrenia. However, little is known regarding the ... ...

Abstract	Background: The endocannabinoid system - comprising cannabinoid receptors, endocannabinoid ligands and their synthesis and inactivation enzymes - has been widely implicated in the pathophysiology of schizophrenia. However, little is known regarding the status of the different elements of the endocannabinoid system in the brain of schizophrenic patients. We have previously reported altered endocannabinoid levels in the postmortem brain of subjects with schizophrenia compared with matched controls. Aims: Our aim was to further examine the status of the main elements of the endocannabinoid system in the postmortem prefrontal cortex of the same cohort of subjects. Methods: Gene expression and function of the cannabinoid receptor type-1 (CB1) and the endocannabinoid degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) have been assessed. Results: A significant decrease in Conclusions: The present findings reveal an imbalance in the expression and function of different elements of the endocannabinoid system in schizophrenia. This outcome highlights the relevance of the endocannabinoid system in the pathophysiology of schizophrenia and emphasises its elements as potential targets in the search for new therapeutic strategies.
MeSH term(s)	Adult ; Amidohydrolases/metabolism ; Arachidonic Acids/metabolism ; Carbamates/metabolism ; Endocannabinoids/metabolism ; Female ; Glycerides/metabolism ; Humans ; Male ; Middle Aged ; Monoacylglycerol Lipases/metabolism ; Prefrontal Cortex/metabolism ; Receptor, Cannabinoid, CB1/metabolism ; Schizophrenia/metabolism
Chemical Substances	Arachidonic Acids ; Carbamates ; Endocannabinoids ; Glycerides ; Receptor, Cannabinoid, CB1 ; glyceryl 2-arachidonate (8D239QDW64) ; Monoacylglycerol Lipases (EC 3.1.1.23) ; Amidohydrolases (EC 3.5.-) ; fatty-acid amide hydrolase (EC 3.5.1.-)
Language	English
Publishing date	2019-06-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639313-5
ISSN	1461-7285 ; 0269-8811
ISSN (online)	1461-7285
ISSN	0269-8811
DOI	10.1177/0269881119857205
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Article ; Online: THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Nuclear hormone receptors.

Alexander, Stephen Ph / Cidlowski, John A / Kelly, Eamonn / Mathie, Alistair / Peters, John A / Veale, Emma L / Armstrong, Jane F / Faccenda, Elena / Harding, Simon D / Pawson, Adam J / Southan, Christopher / Davies, Jamie A / Coons, Laurel / Fuller, Peter J / Korach, Kenneth S / Young, Morag J

British journal of pharmacology

2021 Volume 178 Suppl 1, Page(s) S246–S263

Abstract: The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective ... ...

Abstract	The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15540. Nuclear hormone receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, catalytic receptors, enzymes 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. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
MeSH term(s)	Databases, Pharmaceutical ; Humans ; Ligands ; Membrane Transport Proteins ; Pharmacology ; Receptors, Cytoplasmic and Nuclear ; Receptors, G-Protein-Coupled
Chemical Substances	Ligands ; Membrane Transport Proteins ; Receptors, Cytoplasmic and Nuclear ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2021-09-16
Publishing country	England
Document type	Journal Article
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.15540
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Article ; Online: Oleamide activates peroxisome proliferator-activated receptor gamma (PPARγ) in vitro

Dionisi Mauro / Alexander Stephen PH / Bennett Andrew J

Lipids in Health and Disease, Vol 11, Iss 1, p

2012 Volume 51

Abstract: Abstract Background Oleamide (ODA) is a fatty acid primary amide first identified in the cerebrospinal fluid of sleep-deprived cats, which exerts effects on vascular and neuronal tissues, with a variety of molecular targets including cannabinoid ... ...

Abstract	Abstract Background Oleamide (ODA) is a fatty acid primary amide first identified in the cerebrospinal fluid of sleep-deprived cats, which exerts effects on vascular and neuronal tissues, with a variety of molecular targets including cannabinoid receptors and gap junctions. It has recently been reported to exert a hypolipidemic effect in hamsters. Here, we have investigated the nuclear receptor family of peroxisome proliferator-activated receptors (PPARs) as potential targets for ODA action. Results Activation of PPARα, PPARβ and PPARγ was assessed using recombinant expression in Chinese hamster ovary cells with a luciferase reporter gene assay. Direct binding of ODA to the ligand binding domain of each of the three PPARs was monitored in a cell-free fluorescent ligand competition assay. A well-established assay of PPARγ activity, the differentiation of 3T3-L1 murine fibroblasts into adipocytes, was assessed using an Oil Red O uptake-based assay. ODA, at 10 and 50 μM, was able to transactivate PPARα, PPARβ and PPARγ receptors. ODA bound to the ligand binding domain of all three PPARs, although complete displacement of fluorescent ligand was only evident for PPARγ, at which an IC 50 value of 38 μM was estimated. In 3T3-L1 cells, ODA, at 10 and 20 μM, induced adipogenesis. Conclusions We have, therefore, identified a novel site of action of ODA through PPAR nuclear receptors and shown how ODA should be considered as a weak PPARγ ligand in vitro .
Keywords	Oleamide ; Peroxisome proliferator ; PPAR ; Endocannabinoids ; Physiology ; QP1-981 ; Science ; Q ; DOAJ:Physiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
Subject code	570
Language	English
Publishing date	2012-05-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Down-Regulation of Hippocampal Genes Regulating Dopaminergic, GABAergic, and Glutamatergic Function Following Combined Neonatal Phencyclidine and Post-Weaning Social Isolation of Rats as a Neurodevelopmental Model for Schizophrenia.

Gaskin, Philip Lr / Toledo-Rodriguez, Maria / Alexander, Stephen Ph / Fone, Kevin Cf

The international journal of neuropsychopharmacology

2016 Volume 19, Issue 11

Abstract: Background: Dysfunction of dopaminergic, GABAergic, and glutamatergic function underlies many core symptoms of schizophrenia. Combined neonatal injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP), and post-weaning ... ...

Abstract	Background: Dysfunction of dopaminergic, GABAergic, and glutamatergic function underlies many core symptoms of schizophrenia. Combined neonatal injection of the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP), and post-weaning social isolation of rats produces a behavioral syndrome with translational relevance to several core symptoms of schizophrenia. This study uses DNA microarray to characterize alterations in hippocampal neurotransmitter-related gene expression and examines the ability of the sodium channel blocker, lamotrigine, to reverse behavioral changes in this model. Methods: Fifty-four male Lister-hooded rat pups either received phencyclidine (PCP, 10mg/kg, s.c.) on post-natal days (PND) 7, 9, and 11 before being weaned on PND 23 into separate cages (isolation; PCP-SI; n = 31) or received vehicle injection and group-housing (2-4 per cage; V-GH; n = 23) from weaning. The effect of lamotrigine on locomotor activity, novel object recognition, and prepulse inhibition of acoustic startle was examined (PND 60-75) and drug-free hippocampal gene expression on PND 70. Results: Acute lamotrigine (10-15mg/kg i.p.) reversed the hyperactivity and novel object recognition impairment induced by PCP-SI but had no effect on the prepulse inhibition deficit. Microarray revealed small but significant down-regulation of hippocampal genes involved in glutamate metabolism, dopamine neurotransmission, and GABA receptor signaling and in specific schizophrenia-linked genes, including parvalbumin (PVALB) and GAD67, in PCP-SI rats, which resemble changes reported in schizophrenia. Conclusions: Findings indicate that alterations in dopamine neurotransmission, glutamate metabolism, and GABA signaling may contribute to some of the behavioral deficits observed following PCP-SI, and that lamotrigine may have some utility as an adjunctive therapy to improve certain cognitive deficits symptoms in schizophrenia.
MeSH term(s)	Animals ; Animals, Newborn ; Behavior, Animal/drug effects ; Disease Models, Animal ; Dopaminergic Neurons/drug effects ; Dopaminergic Neurons/metabolism ; GABAergic Neurons/drug effects ; GABAergic Neurons/metabolism ; Gene Expression Profiling/methods ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Glutamic Acid/metabolism ; Hippocampus/drug effects ; Hippocampus/metabolism ; Hippocampus/physiopathology ; Lamotrigine ; Locomotion ; Male ; Oligonucleotide Array Sequence Analysis ; Phencyclidine ; Phenotype ; Prepulse Inhibition ; Rats, Inbred Strains ; Recognition, Psychology ; Reflex, Startle ; Schizophrenia/chemically induced ; Schizophrenia/drug therapy ; Schizophrenia/genetics ; Schizophrenia/metabolism ; Schizophrenic Psychology ; Social Isolation ; Sodium Channel Blockers/pharmacology ; Synaptic Transmission ; Time Factors ; Triazines/pharmacology ; Weaning
Chemical Substances	Sodium Channel Blockers ; Triazines ; Glutamic Acid (3KX376GY7L) ; Phencyclidine (J1DOI7UV76) ; Lamotrigine (U3H27498KS)
Language	English
Publishing date	2016-12-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1440129-0
ISSN	1469-5111 ; 1461-1457
ISSN (online)	1469-5111
ISSN	1461-1457
DOI	10.1093/ijnp/pyw062
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Article ; Online: Randomised, cOntrolled Multicentre trial of 26 weeks subcutaneous liraglutide (a glucagon-like peptide-1 receptor Agonist), with or without contiNuous positive airway pressure (CPAP), in patients with type 2 diabetes mellitus (T2DM) and obstructive sleep apnoEa (OSA) (ROMANCE): study protocol assessing the effects of weight loss on the apnea-hypnoea index (AHI).

Sprung, Victoria S / Kemp, Graham J / Wilding, John Ph / Adams, Valerie / Murphy, Kieran / Burgess, Malcolm / Emegbo, Stephen / Thomas, Matthew / Needham, Alexander J / Weimken, Andrew / Schwab, Richard J / Manuel, Ari / Craig, Sonya E / Cuthbertson, Daniel J

BMJ open

2020 Volume 10, Issue 7, Page(s) e038856

Abstract: Introduction: Obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) often occur concurrently, and untreated OSA may potentially amplify the high risk of cardiovascular disease in T2DM. Compliance with continuous positive airway pressure ( ... ...

Abstract	Introduction: Obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) often occur concurrently, and untreated OSA may potentially amplify the high risk of cardiovascular disease in T2DM. Compliance with continuous positive airway pressure (CPAP), the conventional treatment for OSA, can be poor and considering weight loss is the most effective treatment for OSA. This trial examines whether the glucagon-like peptide-1 receptor agonist liraglutide, a glucose-lowering therapy associated with significant weight loss used in T2DM, can improve the severity and symptoms of OSA. Methods and analysis: This is an outpatient, single-centred, open-labelled, prospective, phase IV randomised controlled trial in a two-by-two factorial design. One hundred and thirty-two patients with newly diagnosed OSA (apnoea-hypopnoea index (AHI) ≥15 events/hour), and existing obesity and T2DM (glycated haemoglobin (HbA Ethical approval: The study has been approved by the North West Liverpool Central Research Ethics Committee (14/NW/1019) and it is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Trial registration numbers: ISRCTN16250774. EUDRACT No. 2014-000988-41. UTN U1111-1139-0677.
MeSH term(s)	Continuous Positive Airway Pressure ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Glucagon-Like Peptide-1 Receptor ; Humans ; Liraglutide/therapeutic use ; Multicenter Studies as Topic ; Prospective Studies ; Quality of Life ; Randomized Controlled Trials as Topic ; Sleep Apnea, Obstructive/complications ; Sleep Apnea, Obstructive/therapy ; Treatment Outcome ; Weight Loss
Chemical Substances	Glucagon-Like Peptide-1 Receptor ; Liraglutide (839I73S42A)
Language	English
Publishing date	2020-07-22
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2020-038856
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Article ; Online: THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Transporters.

Alexander, Stephen Ph / Kelly, Eamonn / Mathie, Alistair / Peters, John A / Veale, Emma L / Armstrong, Jane F / Faccenda, Elena / Harding, Simon D / Pawson, Adam J / Southan, Christopher / Davies, Jamie A / Amarosi, Laura / Anderson, Catriona M H / Beart, Philip Mark / Broer, Stefan / Dawson, Paul A / Hagenbuch, Bruno / Hammond, James R / Inui, Ken-Ichi /

Kanai, Yoshikatsu / Kemp, Stephan / Stewart, Gavin / Thwaites, David T / Verri, Tiziano

British journal of pharmacology

2021 Volume 178 Suppl 1, Page(s) S412–S513

Abstract	The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15543. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic 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. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
MeSH term(s)	Databases, Pharmaceutical ; Humans ; Ion Channels ; Ligands ; Pharmacology ; Receptors, Cytoplasmic and Nuclear ; Receptors, G-Protein-Coupled
Chemical Substances	Ion Channels ; Ligands ; Receptors, Cytoplasmic and Nuclear ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2021-09-16
Publishing country	England
Document type	Journal Article
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.15543
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