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Pharmacological Reviews

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https://www.readbyqxmd.com/read/30209181/the-psychopharmacology-of-effort-related-decision-making-dopamine-adenosine-and-insights-into-the-neurochemistry-of-motivation
#1
REVIEW
John D Salamone, Mercè Correa, Sarah Ferrigno, Jen-Hau Yang, Renee A Rotolo, Rose E Presby
Effort-based decision making is studied using tasks that offer choices between high-effort options leading to more highly valued reinforcers versus low-effort/low-reward options. These tasks have been used to study the involvement of neural systems, including mesolimbic dopamine and related circuits, in effort-related aspects of motivation. Moreover, such tasks are useful as animal models of some of the motivational symptoms that are seen in people with depression, schizophrenia, Parkinson's disease, and other disorders...
October 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/30087160/anti-obesity-therapy-from-rainbow-pills-to-polyagonists
#2
REVIEW
T D Müller, C Clemmensen, B Finan, R D DiMarchi, M H Tschöp
With their ever-growing prevalence, obesity and diabetes represent major health threats of our society. Based on estimations by the World Health Organization, approximately 300 million people will be obese in 2035. In 2015 alone there were more than 1.6 million fatalities attributable to hyperglycemia and diabetes. In addition, treatment of these diseases places an enormous burden on our health care system. As a result, the development of pharmacotherapies to tackle this life-threatening pandemic is of utmost importance...
October 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29945900/adverse-neuropsychiatric-events-and-recreational-use-of-efavirenz-and-other-hiv-1-antiretroviral-drugs
#3
REVIEW
Dhwanil A Dalwadi, Luis Ozuna, Brian H Harvey, Michelle Viljoen, John A Schetz
Efavirenz is a highly effective HIV-1 antiretroviral; however, it is also frequently associated with neuropsychiatric adverse events (NPAE) that include abnormal dreams, sleep disturbances, nervousness, anxiety, depression, and dizziness. The incidence of NPAEs upon initiation of treatment with efavirenz-containing medications is high, exceeding 50% in most studies. Although the NPAEs tend to decrease after the first month in many patients, they persist for long periods of time in others. Efavirenz-based treatment is generally well-tolerated in children, although some experience persistent concentration problems, as well as sleep disturbances, psychotic reactions, and seizures...
July 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29945899/modulating-neural-circuits-with-transcranial-magnetic-stimulation-implications-for-addiction-treatment-development
#4
REVIEW
Colleen A Hanlon, Logan T Dowdle, J Scott Henderson
Although the last 50 years of clinical and preclinical research have demonstrated that addiction is a brain disease, we still have no neural circuit-based treatments for substance dependence or cue reactivity at large. Now, for the first time, it appears that a noninvasive brain stimulation technique known as transcranial magnetic stimulation (TMS), which is Food and Drug Administration approved to treat depression, may be the first tool available to fill this critical void in addiction treatment development...
July 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29945898/ketamine-and-ketamine-metabolite-pharmacology-insights-into-therapeutic-mechanisms
#5
REVIEW
Panos Zanos, Ruin Moaddel, Patrick J Morris, Lace M Riggs, Jaclyn N Highland, Polymnia Georgiou, Edna F R Pereira, Edson X Albuquerque, Craig J Thomas, Carlos A Zarate, Todd D Gould
Ketamine, a racemic mixture consisting of ( S )- and ( R )-ketamine, has been in clinical use since 1970. Although best characterized for its dissociative anesthetic properties, ketamine also exerts analgesic, anti-inflammatory, and antidepressant actions. We provide a comprehensive review of these therapeutic uses, emphasizing drug dose, route of administration, and the time course of these effects. Dissociative, psychotomimetic, cognitive, and peripheral side effects associated with short-term or prolonged exposure, as well as recreational ketamine use, are also discussed...
July 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29941461/trace-amines-and-their-receptors
#6
REVIEW
Raul R Gainetdinov, Marius C Hoener, Mark D Berry
Trace amines are endogenous compounds classically regarded as comprising β -phenylethyalmine, p -tyramine, tryptamine, p -octopamine, and some of their metabolites. They are also abundant in common foodstuffs and can be produced and degraded by the constitutive microbiota. The ability to use trace amines has arisen at least twice during evolution, with distinct receptor families present in invertebrates and vertebrates. The term "trace amine" was coined to reflect the low tissue levels in mammals; however, invertebrates have relatively high levels where they function like mammalian adrenergic systems, involved in "fight-or-flight" responses...
July 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29925522/platelet-signaling-and-disease-targeted-therapy-for-thrombosis-and-other-related-diseases
#7
REVIEW
Jennifer Yeung, Wenjie Li, Michael Holinstat
Platelets are essential for clotting in the blood and maintenance of normal hemostasis. Under pathologic conditions such as atherosclerosis, vascular injury often results in hyperactive platelet activation, resulting in occlusive thrombus formation, myocardial infarction, and stroke. Recent work in the field has elucidated a number of platelet functions unique from that of maintaining hemostasis, including regulation of tumor growth and metastasis, inflammation, infection, and immune response. Traditional therapeutic targets for inhibiting platelet activation have primarily been limited to cyclooxygenase-1, integrin α IIb β 3 , and the P2Y12 receptor...
July 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29921647/mechanisms-and-drug-development-in-atrial-fibrillation
#8
REVIEW
David Calvo, David Filgueiras-Rama, José Jalife
Atrial fibrillation is a highly prevalent cardiac arrhythmia and the most important cause of embolic stroke. Although genetic studies have identified an increasing assembly of AF-related genes, the impact of these genetic discoveries is yet to be realized. In addition, despite more than a century of research and speculation, the molecular and cellular mechanisms underlying AF have not been established, and therapy for AF, particularly persistent AF, remains suboptimal. Current antiarrhythmic drugs are associated with a significant rate of adverse events, particularly proarrhythmia, which may explain why many highly symptomatic AF patients are not receiving any rhythm control therapy...
July 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29884653/international-union-of-basic-and-clinical-pharmacology-civ-the-neurobiology-of-treatment-resistant-depression-from-antidepressant-classifications-to-novel-pharmacological-targets
#9
F Caraci, F Calabrese, R Molteni, L Bartova, M Dold, G M Leggio, C Fabbri, J Mendlewicz, G Racagni, S Kasper, M A Riva, F Drago
Major depressive disorder is one of the most prevalent and life-threatening forms of mental illnesses and a major cause of morbidity worldwide. Currently available antidepressants are effective for most patients, although around 30% are considered treatment resistant (TRD), a condition that is associated with a significant impairment of cognitive function and poor quality of life. In this respect, the identification of the molecular mechanisms contributing to TRD represents an essential step for the design of novel and more efficacious drugs able to modify the clinical course of this disorder and increase remission rates in clinical practice...
July 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29871944/genetic-analysis-of-rare-human-variants-of-regulators-of-g-protein-signaling-proteins-and-their-role-in-human-physiology-and-disease
#10
REVIEW
Katherine E Squires, Carolina Montañez-Miranda, Rushika R Pandya, Matthew P Torres, John R Hepler
Regulators of G protein signaling (RGS) proteins modulate the physiologic actions of many neurotransmitters, hormones, and other signaling molecules. Human RGS proteins comprise a family of 20 canonical proteins that bind directly to G protein-coupled receptors/G protein complexes to limit the lifetime of their signaling events, which regulate all aspects of cell and organ physiology. Genetic variations account for diverse human traits and individual predispositions to disease. RGS proteins contribute to many complex polygenic human traits and pathologies such as hypertension, atherosclerosis, schizophrenia, depression, addiction, cancers, and many others...
July 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29669750/current-challenges-and-opportunities-in-treating-glioblastoma
#11
Andrea Shergalis, Armand Bankhead, Urarika Luesakul, Nongnuj Muangsin, Nouri Neamati
Glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, has a high mortality rate despite extensive efforts to develop new treatments. GBM exhibits both intra- and intertumor heterogeneity, lending to resistance and eventual tumor recurrence. Large-scale genomic and proteomic analysis of GBM tumors has uncovered potential drug targets. Effective and "druggable" targets must be validated to embark on a robust medicinal chemistry campaign culminating in the discovery of clinical candidates...
July 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29514871/interindividual-differences-in-caffeine-metabolism-and-factors-driving-caffeine-consumption
#12
REVIEW
Astrid Nehlig
Most individuals adjust their caffeine intake according to the objective and subjective effects induced by the methylxanthine. However, to reach the desired effects, the quantity of caffeine consumed varies largely among individuals. It has been known for decades that the metabolism, clearance, and pharmacokinetics of caffeine is affected by many factors such as age, sex and hormones, liver disease, obesity, smoking, and diet. Caffeine also interacts with many medications. All these factors will be reviewed in the present document and discussed in light of the most recent data concerning the genetic variability affecting caffeine levels and effects at the pharmacokinetic and pharmacodynamic levels that both critically drive the level of caffeine consumption...
April 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29507103/transcription-factor-nrf2-as-a-therapeutic-target-for-chronic-diseases-a-systems-medicine-approach
#13
REVIEW
Antonio Cuadrado, Gina Manda, Ahmed Hassan, María José Alcaraz, Coral Barbas, Andreas Daiber, Pietro Ghezzi, Rafael León, Manuela G López, Baldo Oliva, Marta Pajares, Ana I Rojo, Natalia Robledinos-Antón, Angela M Valverde, Emre Guney, Harald H H W Schmidt
Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome)...
April 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29500312/etiology-and-pharmacology-of-neuropathic-pain
#14
REVIEW
Sascha R A Alles, Peter A Smith
Injury to or disease of the nervous system can invoke chronic and sometimes intractable neuropathic pain. Many parallel, interdependent, and time-dependent processes, including neuroimmune interactions at the peripheral, supraspinal, and spinal levels, contribute to the etiology of this "disease of pain." Recent work emphasizes the roles of colony-stimulating factor 1, ATP, and brain-derived neurotrophic factor. Excitatory processes are enhanced, and inhibitory processes are attenuated in the spinal dorsal horn and throughout the somatosensory system...
April 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29496890/neuroimmune-axes-of-the-blood-brain-barriers-and-blood-brain-interfaces-bases-for-physiological-regulation-disease-states-and-pharmacological-interventions
#15
REVIEW
Michelle A Erickson, William A Banks
Central nervous system (CNS) barriers predominantly mediate the immune-privileged status of the brain, and are also important regulators of neuroimmune communication. It is increasingly appreciated that communication between the brain and immune system contributes to physiologic processes, adaptive responses, and disease states. In this review, we discuss the highly specialized features of brain barriers that regulate neuroimmune communication in health and disease. In section I , we discuss the concept of immune privilege, provide working definitions of brain barriers, and outline the historical work that contributed to the understanding of CNS barrier functions...
April 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29487084/biomarkers-for-in-vivo-assessment-of-transporter-function
#16
REVIEW
Fabian Müller, Ashish Sharma, Jörg König, Martin F Fromm
Drug-drug interactions are a major concern not only during clinical practice, but also in drug development. Due to limitations of in vitro-in vivo predictions of transporter-mediated drug-drug interactions, multiple clinical Phase I drug-drug interaction studies may become necessary for a new molecular entity to assess potential drug interaction liabilities. This is a resource-intensive process and exposes study participants, who frequently are healthy volunteers without benefit from study treatment, to the potential risks of a new drug in development...
April 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29487083/drugs-for-insomnia-beyond-benzodiazepines-pharmacology-clinical-applications-and-discovery
#17
REVIEW
Tobias Atkin, Stefano Comai, Gabriella Gobbi
Although the GABAergic benzodiazepines (BZDs) and Z-drugs (zolpidem, zopiclone, and zaleplon) are FDA-approved for insomnia disorders with a strong evidence base, they have many side effects, including cognitive impairment, tolerance, rebound insomnia upon discontinuation, car accidents/falls, abuse, and dependence liability. Consequently, the clinical use of off-label drugs and novel drugs that do not target the GABAergic system is increasing. The purpose of this review is to analyze the neurobiological and clinical evidence of pharmacological treatments of insomnia, excluding the BZDs and Z-drugs...
April 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29279348/international-union-of-basic-and-clinical-pharmacology-ciii-chemerin-receptors-cmklr1-chemerin-1-and-gpr1-chemerin-2-nomenclature-pharmacology-and-function
#18
REVIEW
Amanda J Kennedy, Anthony P Davenport
Chemerin, a chemoattractant protein and adipokine, has been identified as the endogenous ligand for a G protein-coupled receptor encoded by the gene CMKLR1 (also known as ChemR23), and as a consequence the receptor protein was renamed the chemerin receptor in 2013. Since then, chemerin has been identified as the endogenous ligand for a second G protein-coupled receptor, encoded by the gene GPR1 Therefore, the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification recommends that the official name of the receptor protein for chemokine-like receptor 1 (CMKLR1) is chemerin receptor 1, and G protein-coupled receptor 1 is chemerin receptor 2 to follow the convention of naming the receptor protein after the endogenous ligand...
January 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29263209/ion-channels-in-genetic-epilepsy-from-genes-and-mechanisms-to-disease-targeted-therapies
#19
REVIEW
Julia Oyrer, Snezana Maljevic, Ingrid E Scheffer, Samuel F Berkovic, Steven Petrou, Christopher A Reid
Epilepsy is a common and serious neurologic disease with a strong genetic component. Genetic studies have identified an increasing collection of disease-causing genes. The impact of these genetic discoveries is wide reaching-from precise diagnosis and classification of syndromes to the discovery and validation of new drug targets and the development of disease-targeted therapeutic strategies. About 25% of genes identified in epilepsy encode ion channels. Much of our understanding of disease mechanisms comes from work focused on this class of protein...
January 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29247129/wnt-signaling-in-cardiac-and-vascular-disease
#20
REVIEW
Sébastien Foulquier, Evangelos P Daskalopoulos, Gentian Lluri, Kevin C M Hermans, Arjun Deb, W Matthijs Blankesteijn
WNT signaling is an elaborate and complex collection of signal transduction pathways mediated by multiple signaling molecules. WNT signaling is critically important for developmental processes, including cell proliferation, differentiation and tissue patterning. Little WNT signaling activity is present in the cardiovascular system of healthy adults, but reactivation of the pathway is observed in many pathologies of heart and blood vessels. The high prevalence of these pathologies and their significant contribution to human disease burden has raised interest in WNT signaling as a potential target for therapeutic intervention...
January 2018: Pharmacological Reviews
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