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Handbook of Experimental Pharmacology

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https://www.readbyqxmd.com/read/30242482/synthetic-opioids
#1
Patrick M Beardsley, Yan Zhang
Opioid abuse has been a global menace for centuries, but the proliferation of synthetic opioids and their use within this current decade have created epidemic-level harms in some countries. According to the United Nations Office on Drugs and Crime, almost 12 million years were estimated loss of "healthy" life resulting in premature death and disability attributable to global opioid abuse just in 2015. Law enforcement and regulatory authorities have been particularly challenged abating the spread of synthetic opioids because soon after controlling the currently recognized abused opioids, their structures are tweaked, and new entities replace them...
September 22, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30203328/brown-adipose-tissue-development-and-metabolism
#2
Su Myung Jung, Joan Sanchez-Gurmaches, David A Guertin
Brown adipose tissue is well known to be a thermoregulatory organ particularly important in small rodents and human infants, but it was only recently that its existence and significance to metabolic fitness in adult humans have been widely realized. The ability of active brown fat to expend high amounts of energy has raised interest in stimulating thermogenesis therapeutically to treat metabolic diseases related to obesity and type 2 diabetes. In parallel, there has been a surge of research aimed at understanding the biology of rodent and human brown fat development, its remarkable metabolic properties, and the phenomenon of white fat browning, in which white adipocytes can be converted into brown like adipocytes with similar thermogenic properties...
September 11, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30203327/clinical-implications-of-the-star-d-trial
#3
A John Rush, Shailesh Bobby Jain
This chapter provides a synopsis of the clinically relevant findings derived from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and selected ancillary studies appended to the primary trial. The chapter describes the participants, their recruitment and treatment, and the study design, primary outcomes, and clinically informative results. In particular, the chapter describes acute phase response and remission rates from each of the five treatment steps which entail antidepressant monotherapies and combinations, and psychotherapy alone or in combination with an antidepressant...
September 11, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30196446/1-2-diarylethylamine-and-ketamine-based-new-psychoactive-substances
#4
Jason Wallach, Simon D Brandt
While phencyclidine (PCP) and ketamine remain the most well-studied and widely known dissociative drugs, a number of other agents have appeared since the late 1950s and early 1960s, when the pharmacological potential of this class was first realized. For example, hundreds of compounds have been pursued as part of legitimate research efforts to explore these agents. Some of these found their way out of the research labs and onto illicit markets of the 1960s and following decades as PCP analogs. Other "illicit analogs" apparently never appeared in the scientific literature prior to their existence on clandestine markets, thus originating as novel innovations in the minds of clandestine chemists and their colleagues...
September 9, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30194544/other-antidepressants
#5
T E Schwasinger-Schmidt, M Macaluso
This chapter addresses the following FDA-approved medications for the treatment of major depressive disorder available for use in the United States including bupropion, mirtazapine, trazodone, vortioxetine, and vilazodone. These medications do not belong to one of the previously featured classes of antidepressants discussed in the preceding chapters. Each medication featured in this chapter has a unique structure and properties that target diverse receptors in the central nervous system. These diverse targets are distinct from other classes of medications used to treat major depressive disorder...
September 8, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30194543/therapeutic-drug-monitoring-of-antidepressants
#6
Najla Fiaturi, David J Greenblatt
For a number of antidepressants in current clinical use, concentrations in serum or plasma are a more reliable index of target drug concentrations than is dosage. For such drugs, therapeutic drug monitoring (TDM) may be a useful clinical guide for the purpose of maximizing the likelihood of favorable therapeutic outcome while minimizing the probability of clinical ineffectiveness or adverse side effects. TDM is of greatest benefit when a therapeutic range of serum concentrations has been well established. Even if such a range is not definitively determined, TDM can be of help in situations in which patients are refractory to therapy despite adequate or high dosages, when adverse events supervene even with low doses, or when noncompliance with the intended dosage plan is suspected...
September 8, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30194542/responding-to-new-psychoactive-substances-in-the-european-union-early-warning-risk-assessment-and-control-measures
#7
Michael Evans-Brown, Roumen Sedefov
New psychoactive substances (NPS) are drugs that are not controlled by the United Nations international drug control conventions of 1961 and 1971 but that may pose similar threats to public health. Many of them are traded as "legal" replacements to controlled drugs such as cannabis, heroin, benzodiazepines, cocaine, amphetamines, and 3,4-methylenedioxymethamphetamine (MDMA). Driven by globalization, there has been a large increase in the availability and, subsequently, harms caused by these substances over the last decade in Europe...
September 8, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30151722/cgrp-receptor-signalling-pathways
#8
Graeme S Cottrell
Calcitonin gene-related peptide (CGRP) is a promiscuous peptide, similar to many other members of the calcitonin family of peptides. The potential of CGRP to act on many different receptors with differing affinities and efficacies makes deciphering the signalling from the CGRP receptor a challenging task for researchers.Although it is not a typical G protein-coupled receptor (GPCR), in that it is composed not just of a GPCR, the CGRP receptor activates many of the same signalling pathways common for other GPCRs...
August 28, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30141101/fatty-acid-metabolites-as-novel-regulators-of-non-shivering-thermogenesis
#9
Stefanie F Maurer, Sebastian Dieckmann, Karin Kleigrewe, Cécilia Colson, Ez-Zoubir Amri, Martin Klingenspor
Fatty acids are essential contributors to adipocyte-based non-shivering thermogenesis by acting as activators of uncoupling protein 1 and serving as fuel for mitochondrial heat production. Novel evidence suggests a contribution to this thermogenic mechanism by their conversion to bioactive compounds. Mammalian cells produce a plethora of oxylipins and endocannabinoids, some of which have been identified to affect the abundance or thermogenic activity of brown and brite adipocytes. These effectors are produced locally or at distant sites and signal toward thermogenic adipocytes via a direct interaction with these cells or indirectly via secondary mechanisms...
August 24, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30141100/aging-of-brown-and-beige-brite-adipose-tissue
#10
Antonia Graja, Sabrina Gohlke, Tim J Schulz
Brown adipose tissue aging and the concomitant loss of thermogenic capacity have been linked to an inability to maintain normal energy homeostasis in late life. Similarly, the ability of white fat to convert into brite/beige adipose tissue declines. This may ultimately exacerbate the progression of age-related metabolic pathologies, such as insulin resistance and obesity. The depletion of all types of brown adipocytes during aging is well-established and has been described in rodent models as well as humans...
August 24, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30141099/current-role-of-herbal-and-natural-preparations
#11
David Mischoulon, Mark Hyman Rapaport
Depression remains difficult to manage, despite the many registered treatments available. For many depressed individuals, particularly those who have not responded to and/or had adverse effects from standard therapies, herbal and natural medications represent a potentially valuable alternative. This chapter will review several natural remedies used in the treatment of depression. Specific remedies covered include St. John's wort (SJW), S-adenosyl-L-methionine (SAMe), omega-3 fatty acids, rhodiola, and others...
August 24, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30141098/activation-of-human-brown-adipose-tissue-bat-focus-on-nutrition-and-eating
#12
Kirsi A Virtanen
Brown adipose tissue activation occurs most effectively by cold exposure. In the modern world, we do not spend long periods in cold environment, and eating and meals may be other activators of brown fat function. Short-term regulation of brown fat functional activity by eating involves most importantly insulin. Insulin is capable to increase glucose uptake in human brown adipose tissue fivefold to fasting conditions. Oxidative metabolism in brown fat is doubled both by cold and by a meal. Human brown adipose tissue is an insulin-sensitive tissue type, and insulin resistance impairs the function, as is found in obesity...
August 24, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30141097/the-use-of-antidepressants-in-bipolar-depression
#13
John L Beyer
Depression remains a significant debilitating and frequent phase of illness for patients with bipolar disorder. There are few FDA-approved medications for its treatment, only one of which includes a traditional antidepressant (olanzapine-fluoxetine combination), despite studies that demonstrate traditional antidepressants are one of the most commonly prescribed class of medications for bipolar patients in a depressive episode. While traditional antidepressants remain the primary option for treatment of unipolar depression, their use in bipolar depression has been controversial due to a limited efficacy evidence and the concern for potential harm...
August 24, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30135990/epidemiology-of-nps-based-confirmed-overdose-cases-the-strida-project
#14
Anders Helander, Matilda Bäckberg
The Swedish STRIDA project on new psychoactive substances (NPS) monitored the occurrence and health hazards of novel recreational drugs in Sweden through evaluation of analytically confirmed adverse events presenting in emergency departments and intensive care units. During a ~6-year period from 2010 to early 2016, about 2,600 cases of suspected NPS intoxications were included in the project. About 75% of patients were men and the total age range was 8-71 (median 24) years and 57% were 25 years or younger...
August 23, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30105474/phencyclidine-based-new-psychoactive-substances
#15
Jason Wallach, Simon D Brandt
The serendipitous discovery of phencyclidine (PCP) in 1956 sets the stage for significant research efforts that resulted in a plethora of analogs and derivatives designed to explore the biological effects of this class. PCP soon became the prototypical dissociative agent that eventually sneaked through the doors of clinical laboratories and became an established street drug. Estimations suggest that around 14 PCP analogs were identified as "street drugs" in the period between the 1960s and 1990s. Fast forward to the 2000s, and largely facilitated by advancements in electronic forms of communication made possible through the Internet, a variety of new PCP analogs began to attract the attention of communities interested in the collaborative exploration of these substances...
August 14, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30105473/the-chemistry-and-pharmacology-of-synthetic-cannabinoid-receptor-agonist-new-psychoactive-substances-evolution
#16
Samuel D Banister, Mark Connor
Synthetic cannabinoid receptor agonists (SCRAs) are the largest and most structurally diverse class of new psychoactive substances (NPS). Although the earliest SCRA NPS were simply repurposed from historical academic manuscripts or pharmaceutical patents describing cannabinoid ligands, recent examples bear hallmarks of rational design. SCRA NPS manufacturers have applied traditional medicinal chemistry strategies (such as molecular hybridization, bioisosteric replacement, and scaffold hopping) to existing cannabinoid templates in order to generate new molecules that circumvent structure-based legislation...
August 14, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30105472/tricyclic-antidepressants-and-monoamine-oxidase-inhibitors-are-they-too-old-for-a-new-look
#17
Ravikumar Chockalingam, Britt M Gott, Charles R Conway
Through unintentional discovery, monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) were the first antidepressant classes to be used clinically and have been widely available for over half a century. From the 1950s to the 1980s, these two classes of antidepressants were the sole antidepressant tools available to psychiatrists. With the advent of the selective serotonin reuptake inhibitors (SSRIs) in the 1980s and 1990s, the prescribing of the MAOIs and TCAs has fallen significantly worldwide...
August 14, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30105471/fatal-poisonings-associated-with-new-psychoactive-substances
#18
Robert Kronstrand, Davide Guerrieri, Svante Vikingsson, Ariane Wohlfarth, Henrik Gréen
This chapter describes how new psychoactive substances (NPS) have been involved in fatal intoxications from 2010 and onwards. It summarizes the circumstances, antemortem symptoms, and adverse effects that have led to death after ingestion of one or more NPS and tabulates concentrations, and postmortem findings from these intoxications.Consumption of NPS exerts health problems and unknown risks for the users. Data on toxicity of many NPS are scarce or nonexistent and long-term toxicity and risks are still largely unknown...
August 14, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30099625/techniques-and-applications-of-magnetic-resonance-imaging-for-studying-brown-adipose-tissue-morphometry-and-function
#19
Dimitrios C Karampinos, Dominik Weidlich, Mingming Wu, Houchun H Hu, Daniela Franz
The present review reports on the current knowledge and recent findings in magnetic resonance imaging (MRI) and spectroscopy (MRS) of brown adipose tissue (BAT). The work summarizes the features and mechanisms that allow MRI to differentiate BAT from white adipose tissue (WAT) by making use of their distinct morphological appearance and the functional characteristics of BAT. MR is a versatile imaging modality with multiple contrast mechanisms as potential candidates in the study of BAT, targeting properties of 1 H, 13 C, or 129 Xe nuclei...
August 12, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30099624/translational-aspects-of-brown-fat-activation-by-food-derived-stimulants
#20
Takeshi Yoneshiro, Mami Matsushita, Masayuki Saito
Since the rediscovery of brown adipose tissue (BAT) in humans, its energy-dissipating ability has been well-recognized. The negative correlations of BAT activity with adiposity and insulin sensitivity provided an obvious rationale for discerning reliable and practical strategies for stimulating BAT. Though cold exposure or use of pharmacological adrenomimetics can activate BAT, they may have adverse effects. Therefore, determining alternative stimulants of BAT with lower risks such as commonly used food ingredients is highly desirable...
August 12, 2018: Handbook of Experimental Pharmacology
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