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Pharmacological Reviews

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https://read.qxmd.com/read/30587536/dose-response-time-data-analysis-an-underexploited-trinity
#1
REVIEW
Johan Gabrielsson, Robert Andersson, Mats Jirstrand, Stephan Hjorth
The most common approach to in vivo pharmacokinetic and pharmacodynamic analyses involves sequential analysis of the plasma concentration - and response - time data, such that the plasma kinetic model provides an independent function, driving the dynamics. However, in situations when plasma sampling may jeopardize the effect measurements or is scarce, nonexistent, or unlinked to the effect (e.g., in intensive care units, pediatric or frail elderly populations, or drug discovery), focusing on the response-time course alone may be an adequate alternative for pharmacodynamic analyses...
January 2019: Pharmacological Reviews
https://read.qxmd.com/read/30573636/cell-volume-activated-and-volume-correlated-anion-channels-in-mammalian-cells-their-biophysical-molecular-and-pharmacological-properties
#2
REVIEW
Yasunobu Okada, Toshiaki Okada, Kaori Sato-Numata, Md Rafiqul Islam, Yuhko Ando-Akatsuka, Tomohiro Numata, Machiko Kubo, Takahiro Shimizu, Ranohon S Kurbannazarova, Yoshinori Marunaka, Ravshan Z Sabirov
There are a number of mammalian anion channel types associated with cell volume changes. These channel types are classified into two groups: volume-activated anion channels (VAACs) and volume-correlated anion channels (VCACs). VAACs can be directly activated by cell swelling and include the volume-sensitive outwardly rectifying anion channel (VSOR), which is also called the volume-regulated anion channel; the maxi-anion channel (MAC or Maxi-Cl); and the voltage-gated anion channel, chloride channel (ClC)-2...
January 2019: Pharmacological Reviews
https://read.qxmd.com/read/30559245/a-pharmacological-perspective-on-the-study-of-taste
#3
REVIEW
R Kyle Palmer
The study of taste has been guided throughout much of its history by the conceptual framework of psychophysics, where the focus was on quantification of the subjective experience of the taste sensations. By the mid-20th century, data from physiologic studies had accumulated sufficiently to assemble a model for the function of receptors that must mediate the initial stimulus of tastant molecules in contact with the tongue. But the study of taste as a receptor-mediated event did not gain momentum until decades later when the actual receptor proteins and attendant signaling mechanisms were identified and localized to the highly specialized taste-responsive cells of the tongue...
January 2019: Pharmacological Reviews
https://read.qxmd.com/read/30545954/personal-mutanomes-meet-modern-oncology-drug-discovery-and-precision-health
#4
REVIEW
Feixiong Cheng, Han Liang, Atul J Butte, Charis Eng, Ruth Nussinov
Recent remarkable advances in genome sequencing have enabled detailed maps of identified and interpreted genomic variation, dubbed "mutanomes." The availability of thousands of exome/genome sequencing data has prompted the emergence of new challenges in the identification of novel druggable targets and therapeutic strategies. Typically, mutanomes are viewed as one- or two-dimensional. The three-dimensional protein structural view of personal mutanomes sheds light on the functional consequences of clinically actionable mutations revealed in tumor diagnosis and followed up in personalized treatments, in a mutanome-informed manner...
January 2019: Pharmacological Reviews
https://read.qxmd.com/read/30282701/correction-to-ketamine-and-ketamine-metabolite-pharmacology-insights-into-therapeutic-mechanisms
#5
(no author information available yet)
No abstract text is available yet for this article.
October 2018: Pharmacological Reviews
https://read.qxmd.com/read/30275042/international-union-of-basic-and-clinical-pharmacology-cvi-gaba-a-receptor-subtype-and-function-selective-ligands-key-issues-in-translation-to-humans
#6
Werner Sieghart, Miroslav M Savić
GABAA receptors are the major inhibitory transmitter receptors in the brain. They are ligand-gated chloride channels and the site of action of benzodiazepines, barbiturates, neuroactive steroids, anesthetics, and convulsants. GABAA receptors are composed of five subunits that can belong to different subunit classes. The existence of 19 homologous subunits and their distinct regional, cellular, and subcellular distribution gives rise to a large number of GABAA receptor subtypes with distinct pharmacology, which modulate different functions of the brain...
October 2018: Pharmacological Reviews
https://read.qxmd.com/read/30232095/international-union-of-basic-and-clinical-pharmacology-cv-somatostatin-receptors-structure-function-ligands-and-new-nomenclature
#7
Thomas Günther, Giovanni Tulipano, Pascal Dournaud, Corinne Bousquet, Zsolt Csaba, Hans-Jürgen Kreienkamp, Amelie Lupp, Márta Korbonits, Justo P Castaño, Hans-Jürgen Wester, Michael Culler, Shlomo Melmed, Stefan Schulz
Somatostatin, also known as somatotropin-release inhibitory factor, is a cyclopeptide that exerts potent inhibitory actions on hormone secretion and neuronal excitability. Its physiologic functions are mediated by five G protein-coupled receptors (GPCRs) called somatostatin receptor (SST)1-5. These five receptors share common structural features and signaling mechanisms but differ in their cellular and subcellular localization and mode of regulation. SST2 and SST5 receptors have evolved as primary targets for pharmacological treatment of pituitary adenomas and neuroendocrine tumors...
October 2018: Pharmacological Reviews
https://read.qxmd.com/read/30209181/the-psychopharmacology-of-effort-related-decision-making-dopamine-adenosine-and-insights-into-the-neurochemistry-of-motivation
#8
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://read.qxmd.com/read/30087160/anti-obesity-therapy-from-rainbow-pills-to-polyagonists
#9
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://read.qxmd.com/read/29945900/adverse-neuropsychiatric-events-and-recreational-use-of-efavirenz-and-other-hiv-1-antiretroviral-drugs
#10
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://read.qxmd.com/read/29945899/modulating-neural-circuits-with-transcranial-magnetic-stimulation-implications-for-addiction-treatment-development
#11
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://read.qxmd.com/read/29945898/ketamine-and-ketamine-metabolite-pharmacology-insights-into-therapeutic-mechanisms
#12
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://read.qxmd.com/read/29941461/trace-amines-and-their-receptors
#13
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://read.qxmd.com/read/29925522/platelet-signaling-and-disease-targeted-therapy-for-thrombosis-and-other-related-diseases
#14
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://read.qxmd.com/read/29921647/mechanisms-and-drug-development-in-atrial-fibrillation
#15
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://read.qxmd.com/read/29884653/international-union-of-basic-and-clinical-pharmacology-civ-the-neurobiology-of-treatment-resistant-depression-from-antidepressant-classifications-to-novel-pharmacological-targets
#16
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://read.qxmd.com/read/29871944/genetic-analysis-of-rare-human-variants-of-regulators-of-g-protein-signaling-proteins-and-their-role-in-human-physiology-and-disease
#17
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://read.qxmd.com/read/29669750/current-challenges-and-opportunities-in-treating-glioblastoma
#18
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://read.qxmd.com/read/29514871/interindividual-differences-in-caffeine-metabolism-and-factors-driving-caffeine-consumption
#19
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://read.qxmd.com/read/29507103/transcription-factor-nrf2-as-a-therapeutic-target-for-chronic-diseases-a-systems-medicine-approach
#20
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
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