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Pharmacological Reviews

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https://www.readbyqxmd.com/read/28202503/vitamin-d-and-depression-cellular-and-regulatory-mechanisms
#1
REVIEW
Michael J Berridge
Depression is caused by a change in neural activity resulting from an increase in glutamate that drives excitatory neurons and may be responsible for the decline in the activity and number of the GABAergic inhibitory neurons. This imbalance between the excitatory and inhibitory neurons may contribute to the onset of depression. At the cellular level there is an increase in the concentration of intracellular Ca(2+) within the inhibitory neurons that is driven by an increase in entry through the NMDA receptors (NMDARs) and through activation of the phosphoinositide signaling pathway that generates inositol trisphosphate (InsP3) that releases Ca(2+) from the internal stores...
April 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28034912/pharmacology-of-modulators-of-alternative-splicing
#2
REVIEW
David O Bates, Jonathan C Morris, Sebastian Oltean, Lucy F Donaldson
More than 95% of genes in the human genome are alternatively spliced to form multiple transcripts, often encoding proteins with differing or opposing function. The control of alternative splicing is now being elucidated, and with this comes the opportunity to develop modulators of alternative splicing that can control cellular function. A number of approaches have been taken to develop compounds that can experimentally, and sometimes clinically, affect splicing control, resulting in potential novel therapeutics...
January 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28011746/the-pharmacology-of-autonomic-failure-from-hypotension-to-hypertension
#3
REVIEW
Italo Biaggioni
Primary neurodegenerative autonomic disorders are characterized clinically by loss of autonomic regulation of blood pressure. The clinical picture is dominated by orthostatic hypotension, but supine hypertension is also a significant problem. Autonomic failure can result from impairment of central autonomic pathways (multiple system atrophy) or neurodegeneration of peripheral postganglionic autonomic fibers (pure autonomic failure, Parkinson's disease). Pharmacologic probes such as the ganglionic blocker trimethaphan can help us in the understanding of the underlying pathophysiology and diagnosis of these disorders...
January 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/27920219/the-proprotein-convertases-in-hypercholesterolemia-and-cardiovascular-diseases-emphasis-on-proprotein-convertase-subtilisin-kexin-9
#4
REVIEW
Nabil G Seidah, Marianne Abifadel, Stefan Prost, Catherine Boileau, Annik Prat
The secretory proprotein convertase (PC) family comprises nine members, as follows: PC1/3, PC2, furin, PC4, PC5/6, paired basic amino acid cleaving enzyme 4, PC7, subtilisin kexin isozyme 1/site 1 protease (SKI-1/S1P), and PC subtilisin/kexin type 9 (PCSK9). The first seven PCs cleave their substrates at single/paired basic residues and exhibit specific and often essential functions during development and/or in adulthood. The essential SKI-1/S1P cleaves membrane-bound transcription factors at nonbasic residues...
January 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/27677721/proteinases-their-extracellular-targets-and-inflammatory-signaling
#5
REVIEW
Rithwik Ramachandran, Christophe Altier, Katerina Oikonomopoulou, Morley D Hollenberg
Given that over 2% of the human genome codes for proteolytic enzymes and their inhibitors, it is not surprising that proteinases serve many physiologic-pathophysiological roles. In this context, we provide an overview of proteolytic mechanisms regulating inflammation, with a focus on cell signaling stimulated by the generation of inflammatory peptides; activation of the proteinase-activated receptor (PAR) family of G protein-coupled receptors (GPCR), with a mechanism in common with adhesion-triggered GPCRs (ADGRs); and by proteolytic ion channel regulation...
October 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27677720/adolescent-alcohol-exposure-persistently-impacts-adult-neurobiology-and-behavior
#6
Fulton T Crews, Ryan P Vetreno, Margaret A Broadwater, Donita L Robinson
Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative-motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries...
October 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27677719/botanicals-and-their-bioactive-phytochemicals-for-women-s-health
#7
REVIEW
Birgit M Dietz, Atieh Hajirahimkhan, Tareisha L Dunlap, Judy L Bolton
Botanical dietary supplements are increasingly popular for women's health, particularly for older women. The specific botanicals women take vary as a function of age. Younger women will use botanicals for urinary tract infections, especially Vaccinium macrocarpon (cranberry), where there is evidence for efficacy. Botanical dietary supplements for premenstrual syndrome (PMS) are less commonly used, and rigorous clinical trials have not been done. Some examples include Vitex agnus-castus (chasteberry), Angelica sinensis (dong quai), Viburnum opulus/prunifolium (cramp bark and black haw), and Zingiber officinale (ginger)...
October 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27664133/targeting-immune-checkpoints-in-hematologic-malignancies
#8
REVIEW
Gheath Alatrash, Naval Daver, Elizabeth A Mittendorf
The use of antibodies that target immune checkpoint molecules on the surface of T-lymphocytes and/or tumor cells has revolutionized our approach to cancer therapy. Cytotoxic-T-lymphocyte antigen (CTLA-4) and programmed cell death protein 1 (PD-1) are the two most commonly targeted immune checkpoint molecules. Although the role of antibodies that target CTLA-4 and PD-1 has been established in solid tumor malignancies and Food and Drug Administration approved for melanoma and non-small cell lung cancer, there remains a desperate need to incorporate immune checkpoint inhibition in hematologic malignancies...
October 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27037223/mechanisms-of-vascular-smooth-muscle-contraction-and-the-basis-for-pharmacologic-treatment-of-smooth-muscle-disorders
#9
REVIEW
F V Brozovich, C J Nicholson, C V Degen, Yuan Z Gao, M Aggarwal, K G Morgan
The smooth muscle cell directly drives the contraction of the vascular wall and hence regulates the size of the blood vessel lumen. We review here the current understanding of the molecular mechanisms by which agonists, therapeutics, and diseases regulate contractility of the vascular smooth muscle cell and we place this within the context of whole body function. We also discuss the implications for personalized medicine and highlight specific potential target molecules that may provide opportunities for the future development of new therapeutics to regulate vascular function...
April 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/26983688/new-era-of-lipid-lowering-drugs
#10
REVIEW
Philip J Barter, Kerry-Anne Rye
There are several established lipid-modifying agents, including statins, fibrates, niacin, and ezetimibe, that have been shown in randomized clinical outcome trials to reduce the risk of having an atherosclerotic cardiovascular event. However, in many people, the risk of having an event remains unacceptably high despite treatment with these established agents. This has stimulated the search for new therapies designed to reduce residual cardiovascular risk. New approaches that target atherogenic lipoproteins include: 1) inhibition of proprotein convertase subtilisin/kexin type 9 to increase removal of atherogenic lipoproteins from plasma; 2) inhibition of the synthesis of apolipoprotein (apo) B, the main protein component of atherogenic lipoproteins; 3) inhibition of microsomal triglyceride transfer protein to block the formation of atherogenic lipoproteins; 4) inhibition of adenosine triphosphate citrate lyase to inhibit the synthesis of cholesterol; 5) inhibition of the synthesis of lipoprotein(a), a factor known to cause atherosclerosis; 6) inhibition of apoC-III to reduce triglyceride-rich lipoproteins and to enhance high-density lipoprotein (HDL) functionality; and 7) inhibition of cholesteryl ester transfer protein, which not only reduces the concentration of atherogenic lipoproteins but also increases the level and function of the potentially antiatherogenic HDL fraction...
April 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/26956246/nociceptin-orphanin-fq-receptor-structure-signaling-ligands-functions-and-interactions-with-opioid-systems
#11
REVIEW
Lawrence Toll, Michael R Bruchas, Girolamo Calo', Brian M Cox, Nurulain T Zaveri
The NOP receptor (nociceptin/orphanin FQ opioid peptide receptor) is the most recently discovered member of the opioid receptor family and, together with its endogenous ligand, N/OFQ, make up the fourth members of the opioid receptor and opioid peptide family. Because of its more recent discovery, an understanding of the cellular and behavioral actions induced by NOP receptor activation are less well developed than for the other members of the opioid receptor family. All of these factors are important because NOP receptor activation has a clear modulatory role on mu opioid receptor-mediated actions and thereby affects opioid analgesia, tolerance development, and reward...
April 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/26956245/endothelin
#12
REVIEW
Anthony P Davenport, Kelly A Hyndman, Neeraj Dhaun, Christopher Southan, Donald E Kohan, Jennifer S Pollock, David M Pollock, David J Webb, Janet J Maguire
The endothelins comprise three structurally similar 21-amino acid peptides. Endothelin-1 and -2 activate two G-protein coupled receptors, ETA and ETB, with equal affinity, whereas endothelin-3 has a lower affinity for the ETA subtype. Genes encoding the peptides are present only among vertebrates. The ligand-receptor signaling pathway is a vertebrate innovation and may reflect the evolution of endothelin-1 as the most potent vasoconstrictor in the human cardiovascular system with remarkably long lasting action...
April 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/26931125/correction-to-psychedelics
#13
(no author information available yet)
No abstract text is available yet for this article.
April 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/26841800/psychedelics
#14
REVIEW
David E Nichols
Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action...
April 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/26772794/sex-differences-in-animal-models-focus-on-addiction
#15
REVIEW
Jill B Becker, George F Koob
The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating...
April 2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27630114/glucagon-like-peptide-1-and-its-class-b-g-protein-coupled-receptors-a-long-march-to-therapeutic-successes
#16
REVIEW
Chris de Graaf, Dan Donnelly, Denise Wootten, Jesper Lau, Patrick M Sexton, Laurence J Miller, Jung-Mo Ahn, Jiayu Liao, Madeleine M Fletcher, Dehua Yang, Alastair J H Brown, Caihong Zhou, Jiejie Deng, Ming-Wei Wang
The glucagon-like peptide (GLP)-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secreted from three major tissues in humans, enteroendocrine L cells in the distal intestine, α cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity...
2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27591044/kinase-dependent-regulation-of-monoamine-neurotransmitter-transporters
#17
REVIEW
Daniel P Bermingham, Randy D Blakely
Modulation of neurotransmission by the monoamines dopamine (DA), norepinephrine (NE), and serotonin (5-HT) is critical for normal nervous system function. Precise temporal and spatial control of this signaling in mediated in large part by the actions of monoamine transporters (DAT, NET, and SERT, respectively). These transporters act to recapture their respective neurotransmitters after release, and disruption of clearance and reuptake has significant effects on physiology and behavior and has been linked to a number of neuropsychiatric disorders...
2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27363442/manipulating-angiogenesis-by-targeting-endothelial-metabolism-hitting-the-engine-rather-than-the-drivers-a-new-perspective
#18
REVIEW
Lucas Treps, Lena-Christin Conradi, Ulrike Harjes, Peter Carmeliet
Excessive angiogenesis (i.e., the formation of new blood vessels) contributes to different pathologies, among them cancer and ocular disorders. Conversely, dysfunction of endothelial cells (ECs) contributes to cardiovascular complications, as is the case in diabetes. Inhibition of pathologic angiogenesis in blinding eye disease and cancer by targeting growth factors such as vascular endothelial growth factor has become an accepted therapeutic strategy. However, recent studies also unveiled the emerging importance of EC metabolism in controlling angiogenesis...
2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27363441/the-nucleus-accumbens-mechanisms-of-addiction-across-drug-classes-reflect-the-importance-of-glutamate-homeostasis
#19
REVIEW
M D Scofield, J A Heinsbroek, C D Gipson, Y M Kupchik, S Spencer, A C W Smith, D Roberts-Wolfe, P W Kalivas
The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical and limbic structures to mediate goal-directed behaviors. Chronic exposure to several classes of drugs of abuse disrupts plasticity in this region, allowing drug-associated cues to engender a pathologic motivation for drug seeking. A number of alterations in glutamatergic transmission occur within the nucleus accumbens after withdrawal from chronic drug exposure. These drug-induced neuroadaptations serve as the molecular basis for relapse vulnerability...
2016: Pharmacological Reviews
https://www.readbyqxmd.com/read/27363440/kinases-as-novel-therapeutic-targets-in-asthma-and-chronic-obstructive-pulmonary-disease
#20
REVIEW
Peter J Barnes
Multiple kinases play a critical role in orchestrating the chronic inflammation and structural changes in the respiratory tract of patients with asthma and chronic obstructive pulmonary disease (COPD). Kinases activate signaling pathways that lead to contraction of airway smooth muscle and release of inflammatory mediators (such as cytokines, chemokines, growth factors) as well as cell migration, activation, and proliferation. For this reason there has been great interest in the development of kinase inhibitors as anti-inflammatory therapies, particular where corticosteroids are less effective, as in severe asthma and COPD...
2016: Pharmacological Reviews
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