1,618 results match your criteria Handbook of Experimental Pharmacology [Journal]


N/OFQ-NOP System in Peripheral and Central Immunomodulation.

Handb Exp Pharmacol 2019 Feb 16. Epub 2019 Feb 16.

Department of Cardiovascular Sciences, Anaesthesia Critical Care and Pain Management, University of Leicester, Leicester Royal Infirmary, Leicester, UK.

Classical opioids (μ: mu, MOP; δ: delta, DOP and κ: kappa, KOP) variably affect immune function; they are immune depressants and there is good clinical evidence in the periphery. In addition, there is evidence for a central role in the control of a number of neuropathologies, e.g. Read More

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http://link.springer.com/10.1007/164_2018_203
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http://dx.doi.org/10.1007/164_2018_203DOI Listing
February 2019
4 Reads

N/OFQ-NOP System and Airways.

Handb Exp Pharmacol 2019 Feb 7. Epub 2019 Feb 7.

Department of Experimental Medicine, Section of Pharmacology L. Donatelli, University of Campania "L. Vanvitelli", Naples, Italy.

Asthma is a heterogeneous chronic inflammatory disease of the airways. The most prevalent form is atopic asthma, which is initiated by the exposure to (inhaled) allergens. Intermittent attacks of breathlessness, airways hyperresponsiveness, wheezing, coughing, and resultant allergen-specific immune responses characterize the disease. Read More

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http://dx.doi.org/10.1007/164_2018_202DOI Listing
February 2019
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Pharmacological Assays for Investigating the NOP Receptor.

Handb Exp Pharmacol 2019 Feb 7. Epub 2019 Feb 7.

Section of Pharmacology, Department of Medical Sciences, National Institute of Neurosciences, University of Ferrara, Ferrara, Italy.

The nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) is a G protein-coupled receptor involved in the regulation of several physiological functions and pathological conditions. Thus, researchers from academia and industry are pursuing NOP to discover and study novel pharmacological entities. In a multidisciplinary effort of pharmacologists, medicinal chemists, and molecular and structural biologists the mechanisms of NOP activation and inhibition have been, at least partially, disentangled. Read More

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http://link.springer.com/10.1007/164_2018_200
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http://dx.doi.org/10.1007/164_2018_200DOI Listing
February 2019
3 Reads

Role of CGRP in Migraine.

Authors:
Lars Edvinsson

Handb Exp Pharmacol 2019 Feb 7. Epub 2019 Feb 7.

Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Lund, Sweden.

Migraine is a common neurological disorder that afflicts up to 15% of the adult population in most countries, with predominance in females. It is characterized by episodic, often disabling headache, photophobia and phonophobia, autonomic symptoms (nausea and vomiting), and in a subgroup an aura in the beginning of the attack. Although still debated, many researchers consider migraine to be a disorder in which CNS dysfunction plays a pivotal role while various parts of the trigeminal system are necessary for the expression of associated symptoms. Read More

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http://dx.doi.org/10.1007/164_2018_201DOI Listing
February 2019
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Therapeutic Approaches for NOP Receptor Antagonists in Neurobehavioral Disorders: Clinical Studies in Major Depressive Disorder and Alcohol Use Disorder with BTRX-246040 (LY2940094).

Handb Exp Pharmacol 2019 Jan 31. Epub 2019 Jan 31.

BlackThorn Therapeutics, San Francisco, CA, USA.

Conventional antidepressants increase the efflux of biogenic amine neurotransmitters (the monoamine hypothesis of depression) in the central nervous system (CNS) and are the principle drugs used to treat major depressive disorder (MDD). However, the lack of efficacy in some patients, the slow onset of action, and the side effect profiles of existing antidepressants necessitate the exploration of additional treatment options. The discovery of the nociceptin/orphanin FQ peptide NOP receptor (N/OFQ-NOP receptor) system and its characterization in preclinical biological and pharmacological stress-related conditions supports the potential antidepressant and anti-stress properties of a NOP receptor antagonist for the treatment of neurobehavioral disorders. Read More

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http://dx.doi.org/10.1007/164_2018_186DOI Listing
January 2019

NOP-Targeted Peptide Ligands.

Handb Exp Pharmacol 2019 Jan 29. Epub 2019 Jan 29.

Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.

The nociceptin/orphanin FQ (N/OFQ)-N/OFQ peptide (NOP) receptor system is widely distributed at both the peripheral and central level where it modulates important biological functions with increasing therapeutic implications. This chapter wants to provide a comprehensive and updated overview focused on the available structure-activity relationship studies on NOP receptor peptide ligands developed through different rational approaches. Punctual modifications and cyclizations of the N/OFQ sequence have been properly combined furnishing potent NOP selective ligands with different pharmacological activities (full and partial agonists, pure antagonists) and enhanced metabolic stability in vivo. Read More

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http://dx.doi.org/10.1007/164_2018_198DOI Listing
January 2019
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The History of N/OFQ and the NOP Receptor.

Handb Exp Pharmacol 2019 Jan 29. Epub 2019 Jan 29.

Department of Pharmacology and Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USA.

The discovery of nociceptin/orphanin FQ (N/OFQ) marks the genuine start of the reverse pharmacology era, when systematic hunting for ligands of orphan receptors began. The choice of this particular target was no coincidence as the orphan receptor ORL-1 displayed high similarity to known opioid receptors, and thus its elusive ligand held promise to find more than a ligand but a missing opioid peptide. N/OFQ indeed turned out to belong to the opioid peptide family, but with significant pharmacological and functional distinctions. Read More

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http://dx.doi.org/10.1007/164_2018_195DOI Listing
January 2019

Translational Pharmacology and Physiology of Brown Adipose Tissue in Human Disease and Treatment.

Handb Exp Pharmacol 2019 Jan 29. Epub 2019 Jan 29.

Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

Human brown adipose tissue (BAT) is experimentally modeled to better understand the biology of this important metabolic tissue, and also to enable the potential discovery and development of novel therapeutics for obesity and sequelae resulting from the persistent positive energy balance. This chapter focuses on translation into humans of findings and hypotheses generated in nonhuman models of BAT pharmacology. Given the demonstrated challenges of sustainably reducing caloric intake in modern humans, potential solutions to obesity likely lie in increasing energy expenditure. Read More

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http://dx.doi.org/10.1007/164_2018_184DOI Listing
January 2019
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Regulation of the Genes Encoding the ppN/OFQ and NOP Receptor.

Handb Exp Pharmacol 2019 Jan 29. Epub 2019 Jan 29.

Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Bologna, Italy.

Over the years, the ability of N/OFQ-NOP receptor system in modulating several physiological functions, including the release of neurotransmitters, anxiety-like behavior responses, modulation of the reward circuitry, inflammatory signaling, nociception, and motor function, has been examined in several brain regions and at spinal level. This chapter collects information related to the genes encoding the ppN/OFQ and NOP receptor, their regulation, and relative transcriptional control mechanisms. Furthermore, genetic manipulations, polymorphisms, and epigenetic alterations associated with different pathological conditions are discussed. Read More

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http://dx.doi.org/10.1007/164_2018_196DOI Listing
January 2019

NOP Receptor Ligands and Parkinson's Disease.

Handb Exp Pharmacol 2019 Jan 29. Epub 2019 Jan 29.

Department of Medical Sciences, Section of Pharmacology, and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.

Nociceptin/Orphanin FQ (N/OFQ) and its NOP receptor are highly expressed in motor areas of the rodent, nonhuman, and human primate brain, such as primary motor cortex, thalamus, globus pallidus, striatum, and substantia nigra. Endogenous N/OFQ negatively regulates motor behavior and dopamine transmission through NOP receptors expressed by dopaminergic neurons of the substantia nigra compacta. Consistent with the existence of an N/OFQ tone over dopaminergic transmission, blockade of NOP receptor antagonists increases striatal dopamine release. Read More

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http://dx.doi.org/10.1007/164_2018_199DOI Listing
January 2019
1 Read

CGRP in Animal Models of Migraine.

Handb Exp Pharmacol 2019 Jan 29. Epub 2019 Jan 29.

Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USA.

With the approval of calcitonin gene-related peptide (CGRP) and CGRP receptor monoclonal antibodies by the Federal Drug Administration, a new era in the treatment of migraine patients is beginning. However, there are still many unknowns in terms of CGRP mechanisms of action that need to be elucidated to allow new advances in migraine therapies. CGRP has been studied both clinically and preclinically since its discovery. Read More

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http://dx.doi.org/10.1007/164_2018_187DOI Listing
January 2019

Soluble Guanylate Cyclase Stimulators and Activators.

Handb Exp Pharmacol 2019 Jan 29. Epub 2019 Jan 29.

Bayer AG, Pharmaceuticals R&D, Pharma Research Center, Wuppertal, Germany.

When Furchgott, Murad, and Ignarro were honored with the Nobel prize for the identification of nitric oxide (NO) in 1998, the therapeutic implications of this discovery could not be fully anticipated. This was due to the fact that available therapeutics like NO donors did not allow a constant and long-lasting cyclic guanylyl monophosphate (cGMP) stimulation and had a narrow therapeutic window. Now, 20 years later, the stimulator of soluble guanylate cyclase (sGC), riociguat, is on the market and is the only drug approved for the treatment of two forms of pulmonary hypertension (PAH/CTEPH), and a variety of other sGC stimulators and sGC activators are in preclinical and clinical development for additional indications. Read More

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http://dx.doi.org/10.1007/164_2018_197DOI Listing
January 2019
1 Read

Pharmacosynthetic Deconstruction of Sleep-Wake Circuits in the Brain.

Handb Exp Pharmacol 2019 Jan 29. Epub 2019 Jan 29.

Laboratory of Neurophysiology, Université Libre de Bruxelles Neuroscience Institute, ULB-UNI, Brussels, Belgium.

Over the past decade, basic sleep research investigating the circuitry controlling sleep and wakefulness has been boosted by pharmacosynthetic approaches, including chemogenetic techniques using designed receptors exclusively activated by designer drugs (DREADD). DREADD offers a series of tools that selectively control neuronal activity as a way to probe causal relationship between neuronal sub-populations and the regulation of the sleep-wake cycle. Following the path opened by optogenetics, DREADD tools applied to discrete neuronal sub-populations in numerous brain areas quickly made their contribution to the discovery and the expansion of our understanding of critical brain structures involved in a wide variety of behaviors and in the control of vigilance state architecture. Read More

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http://dx.doi.org/10.1007/164_2018_183DOI Listing
January 2019

Calcitonin Gene-Related Peptide Antagonists and Therapeutic Antibodies.

Handb Exp Pharmacol 2019 Jan 29. Epub 2019 Jan 29.

School of Biological Sciences, University of Essex, Colchester, UK.

The calcitonin gene-related peptide (CGRP) receptor is composed of the calcitonin receptor-like receptor (CLR, a class B GPCR) and a single-pass membrane protein known as receptor activity modifying protein type 1 (RAMP1). The levels of the CGRP peptide increase during a migraine attack and infusion of CGRP can provoke a migraine attack. Consequently, there is much interest in inhibiting the actions of CGRP as a way to control migraine. Read More

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http://dx.doi.org/10.1007/164_2018_173DOI Listing
January 2019

Regulation of Inositol Biosynthesis: Balancing Health and Pathophysiology.

Handb Exp Pharmacol 2018 Dec 28. Epub 2018 Dec 28.

Department of Biological Sciences, Wayne State University, Detroit, MI, USA.

Inositol is the precursor for all inositol compounds and is essential for viability of eukaryotic cells. Numerous cellular processes and signaling functions are dependent on inositol compounds, and perturbation of their synthesis leads to a wide range of human diseases. Although considerable research has been directed at understanding the function of inositol compounds, especially phosphoinositides and inositol phosphates, a focus on regulatory and homeostatic mechanisms controlling inositol biosynthesis has been largely neglected. Read More

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http://link.springer.com/10.1007/164_2018_181
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http://dx.doi.org/10.1007/164_2018_181DOI Listing
December 2018
4 Reads

Drug Development in Psychiatry: The Long and Winding Road from Chance Discovery to Rational Development.

Handb Exp Pharmacol 2018 Dec 21. Epub 2018 Dec 21.

University of Kansas School of Medicine-Wichita, Wichita, KS, USA.

Based extensively on tables and figures, this chapter reviews drug development in psychiatry with an emphasis on antidepressants from 1950s to the present and then looks forward to the future. It begins with the chance discovery drugs and then moves to through their rational refinement using structure activity relationships to narrow the pharmacological actions of the drugs to those mediating their antidepressant effects and eliminating the effects on targets that mediate adverse effects. This approach yielded newer antidepressants which compared to older antidepressants are safer and better tolerated but nevertheless do still not treat the approximately 40% of patients with major depression (MD) which is unresponsive to biogenic amine mechanisms of action. Read More

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http://dx.doi.org/10.1007/164_2018_169DOI Listing
December 2018
4 Reads

Role of Phospholipase D-Derived Phosphatidic Acid in Regulated Exocytosis and Neurological Disease.

Handb Exp Pharmacol 2018 Dec 21. Epub 2018 Dec 21.

Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 and Université de Strasbourg, Strasbourg, France.

Lipids play a vital role in numerous cellular functions starting from a structural role as major constituents of membranes to acting as signaling intracellular or extracellular entities. Accordingly, it has been known for decades that lipids, especially those coming from diet, are important to maintain normal physiological functions and good health. On the other side, the exact molecular nature of these beneficial or deleterious lipids, as well as their precise mode of action, is only starting to be unraveled. Read More

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http://dx.doi.org/10.1007/164_2018_180DOI Listing
December 2018

NOP Ligands for the Treatment of Anxiety and Mood Disorders.

Handb Exp Pharmacol 2018 Dec 8. Epub 2018 Dec 8.

Department of Medical Sciences, Section of Pharmacology, and National Institute of Neuroscience, University of Ferrara, Ferrara, Italy.

Many studies point toward the nociceptin/orphanin FQ (N/OFQ) and the N/OFQ peptide receptor (NOP) as targets for the development of innovative drugs for treating anxiety- and mood-related disorders. Evidence supports the view that the activation of NOP receptors with agonists elicits anxiolytic-like effects, while its blockade with NOP antagonists promotes antidepressant-like actions in rodents. Genetic studies showed that NOP receptor knockout mice display an antidepressant-like phenotype, and NOP antagonists are inactive in these animals. Read More

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http://dx.doi.org/10.1007/164_2018_188DOI Listing
December 2018

Exploring the Therapeutic Landscape of Sphingomyelinases.

Handb Exp Pharmacol 2018 Nov 27. Epub 2018 Nov 27.

Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA.

Sphingosine, ceramide, sphingosine-1-phosphate, and other related sphingolipids have emerged as important bioactive molecules involved in a variety of key cellular processes such as cell growth, differentiation, apoptosis, exosome release, and inter- and intracellular cell communication, making the pathways of sphingolipid metabolism a key domain in maintaining cell homeostasis (Hannun and Obeid, Trends Biochem Sci 20:73-77, 1995; Hannun and Obeid, Nat Rev Mol Cell Biol 9:139-150, 2008; Kosaka et al., J Biol Chem 288:10849-10859, 2013). Various studies have determined that these pathways play a central role in regulating intracellular production of ceramide and the other bioactive sphingolipids and hence are an important component of signaling in various diseases such as cancer, diabetes, and neurodegenerative and cardiovascular diseases (Chaube et al. Read More

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http://dx.doi.org/10.1007/164_2018_179DOI Listing
November 2018
3 Reads

Regulatory Small and Long Noncoding RNAs in Brite/Brown Adipose Tissue.

Handb Exp Pharmacol 2018 Nov 27. Epub 2018 Nov 27.

Institute for Diabetes and Cancer (IDC), Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.

Brite/brown adipose tissue (BAT) is a thermogenic tissue able to dissipate energy via non-shivering thermogenesis. It is naturally activated by cold and has been demonstrated to increase thermogenic capacity, elevate energy expenditure, and to ultimately contribute to fat mass reduction. Thus, it emerges as novel therapeutic concept for pharmacological intervention in obesity and other metabolic disorders. Read More

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http://link.springer.com/10.1007/164_2018_123
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http://dx.doi.org/10.1007/164_2018_123DOI Listing
November 2018
9 Reads

Self-Experiments with Psychoactive Substances: A Historical Perspective.

Handb Exp Pharmacol 2018 Nov 27. Epub 2018 Nov 27.

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.

The purpose of this chapter is to highlight the rich tradition of self-experiments (SEs) with psychoactive substances carried out by scientists and therapists for more than a century. Scientifically inspired controlled SEs dominated until the end of the twentieth century, when ethical requirements minimized controlled SEs and "wild" SEs expanded particularly with the emergence of new psychoactive substances. The review focuses on laughing gas (nitrous oxide), cannabis, cocaine, hallucinogens, entactogens, and dissociative hallucinogens. Read More

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http://dx.doi.org/10.1007/164_2018_177DOI Listing
November 2018
1 Read

NMDA Antagonists for Treatment-Resistant Depression.

Authors:
Nuri B Farber

Handb Exp Pharmacol 2018 Nov 27. Epub 2018 Nov 27.

Residency Training, Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.

Fifteen to thirty percent of patients with major depressive disorder do not respond to antidepressants that target the monoaminergic systems. NMDA antagonists are currently being actively investigated as a treatment for these patients. Ketamine is the most widely studied of the compounds. Read More

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http://dx.doi.org/10.1007/164_2018_165DOI Listing
November 2018

Functional Interactions Between Sleep and Circadian Rhythms in Learning and Learning Disabilities.

Handb Exp Pharmacol 2018 Nov 16. Epub 2018 Nov 16.

Biology Department, Stanford University, Stanford, CA, USA.

The propensity for sleep is timed by the circadian system. Many studies have shown that learning and memory performance is affected by circadian phase. And, of course it is well established that critical processes of memory consolidation occur during and depend on sleep. Read More

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http://dx.doi.org/10.1007/164_2018_176DOI Listing
November 2018
9 Reads

Clinical and Experimental Human Sleep-Wake Pharmacogenetics.

Handb Exp Pharmacol 2018 Nov 16. Epub 2018 Nov 16.

Wisconsin Institute for Sleep and Consciousness, University of Wisconsin Madison, Madison, WI, USA.

Sleep and wakefulness are highly complex processes that are elegantly orchestrated by fine-tuned neurochemical changes among neuronal and non-neuronal ensembles, nuclei, and networks of the brain. Important neurotransmitters and neuromodulators regulating the circadian and homeostatic facets of sleep-wake physiology include melatonin, γ-aminobutyric acid, hypocretin, histamine, norepinephrine, serotonin, dopamine, and adenosine. Dysregulation of these neurochemical systems may cause sleep-wake disorders, which are commonly classified into insomnia disorder, parasomnias, circadian rhythm sleep-wake disorders, central disorders of hypersomnolence, sleep-related movement disorders, and sleep-related breathing disorders. Read More

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http://dx.doi.org/10.1007/164_2018_175DOI Listing
November 2018
23 Reads

Sleep- and Wake-Like States in Small Networks In Vivo and In Vitro.

Handb Exp Pharmacol 2018 Nov 16. Epub 2018 Nov 16.

Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.

Wakefulness and sleep are highly complex and heterogeneous processes, involving multiple neurotransmitter systems and a sophisticated interplay between global and local networks of neurons and non-neuronal cells. Macroscopic approaches applied at the level of the whole organism, view sleep as a global behaviour and allow for investigation into aspects such as the effects of insufficient or disrupted sleep on cognitive function, metabolism, thermoregulation and sensory processing. While significant progress has been achieved using such large-scale approaches, the inherent complexity of sleep-wake regulation has necessitated the development of methods which tackle specific aspects of sleep in isolation. Read More

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http://dx.doi.org/10.1007/164_2018_174DOI Listing
November 2018
1 Read

The Nociceptin/Orphanin FQ System and the Regulation of Memory.

Handb Exp Pharmacol 2018 Nov 15. Epub 2018 Nov 15.

Research Center on Animal Cognition (CRCA), Center for Integrative Biology (CBI), Toulouse University, CNRS, UPS, Toulouse, France.

Nociceptin/orphanin FQ (N/OFQ) is an endogenous neuropeptide of 17 amino acids, related to opioid peptides but with its own receptor, distinct from conventional opioid receptors, the ORL1 or NOP receptor. The NOP receptor is a G protein-coupled receptor which activates Gi/o proteins and thus induces an inhibition of neuronal activity. The peptide and its receptor are widely expressed in the central nervous system with a high density of receptors in regions involved in learning and memory. Read More

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http://link.springer.com/10.1007/164_2018_185
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http://dx.doi.org/10.1007/164_2018_185DOI Listing
November 2018
14 Reads

Nociceptin/Orphanin FQ and Urinary Bladder.

Handb Exp Pharmacol 2018 Nov 15. Epub 2018 Nov 15.

Section of Pharmacology, Department of Medical Sciences, and National Institute of Neurosciences, University of Ferrara, Ferrara, Italy.

Following identification as the endogenous ligand for the NOP receptor, nociceptin/orphanin FQ (N/OFQ) has been shown to control several biological functions including the micturition reflex. N/OFQ elicits a robust inhibitory effect on rat micturition by reducing the excitability of the afferent fibers. After intravesical administration N/OFQ increases urodynamic bladder capacity and volume threshold in overactive bladder patients but not in normal subjects. Read More

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http://link.springer.com/10.1007/164_2018_182
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http://dx.doi.org/10.1007/164_2018_182DOI Listing
November 2018
11 Reads

CGRP Discovery and Timeline.

Handb Exp Pharmacol 2018 Nov 15. Epub 2018 Nov 15.

Section of Vascular Biology & Inflammation, School of Cardiovascular Medicine & Sciences, BHF Centre for Cardiovascular Sciences, King's College London, London, UK.

Calcitonin gene-related peptide (CGRP) was discovered over about 35 years ago through molecular biological techniques. Its activity as a vasodilator and the proposal that it was involved in pain processing were then soon established. Today, we are in the interesting situation of having the approval for the clinical use of antagonists and antibodies that have proved to block CGRP activities and benefit migraine. Read More

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http://link.springer.com/10.1007/164_2018_129
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http://dx.doi.org/10.1007/164_2018_129DOI Listing
November 2018
8 Reads

Neuropharmacology of Synthetic Cathinones.

Handb Exp Pharmacol 2018 Nov 8. Epub 2018 Nov 8.

Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.

Synthetic cathinones are derivatives of the naturally occurring compound cathinone, the main psychoactive ingredient in the khat plant Catha edulis. Cathinone is the β-keto analog of amphetamine, and all synthetic cathinones display a β-keto moiety in their structure. Several synthetic cathinones are widely prescribed medications (e. Read More

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http://link.springer.com/10.1007/164_2018_178
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http://dx.doi.org/10.1007/164_2018_178DOI Listing
November 2018
16 Reads

Cancer Evolution as the New Frontier of Precision Medicine.

Handb Exp Pharmacol 2018 ;249:289-297

Division of Experimental Cancer Medicine, Istituto Europeo di Oncologia, Milano, Italy.

New experimental breast cancer therapies directed against novel targets are currently in clinical These experimental agents are likely to be effective for a niche of breast cancers with specific "driver mutations". The ability to perform comprehensive molecular profiling of individual tumors has rapidly expanded over the last few years, and new DNA sequencing technologies require relatively limited quantities of fresh or archived paraffin-embedded or snap-frozen tumor tissue and provide rapid turnaround of sequencing results within a few weeks or less. All these technologies provide an unprecedented opportunity to identify patients with rare "driver" molecular alternations that are candidates for proof-of-concept clinical trials with matched targeted therapy, in the context of basket trials. Read More

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http://dx.doi.org/10.1007/164_2018_147DOI Listing
January 2018

Role of Inflammation in Depression and Treatment Implications.

Handb Exp Pharmacol 2018 Oct 28. Epub 2018 Oct 28.

Emory University School of Medicine, Atlanta, GA, USA.

Approximately one third of depressed patients fail to respond to currently available antidepressant therapies. Therefore, new conceptual frameworks are needed to identify pathophysiologic pathways and neurobiological targets for the development of novel treatment strategies. In this regard, recent evidence suggests that inflammation may contribute to symptoms relevant to a number of psychiatric disorders and particularly depression. Read More

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http://link.springer.com/10.1007/164_2018_166
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http://dx.doi.org/10.1007/164_2018_166DOI Listing
October 2018
10 Reads

Designer Benzodiazepines: Another Class of New Psychoactive Substances.

Handb Exp Pharmacol 2018 Oct 27. Epub 2018 Oct 27.

Institute of Forensic Medicine, Forensic Toxicology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Benzodiazepines have been introduced as medical drugs in the 1960s. They replaced the more toxic barbiturates, which were commonly used for treatment of anxiety or sleep disorders at the time. However, benzodiazepines show a high potential of misuse and dependence. Read More

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http://link.springer.com/10.1007/164_2018_154
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http://dx.doi.org/10.1007/164_2018_154DOI Listing
October 2018
36 Reads

Pharmacogenomics and Biomarkers of Depression.

Handb Exp Pharmacol 2018 Oct 20. Epub 2018 Oct 20.

University of Texas Southwestern, Dallas, TX, USA.

The standard of care for antidepressant treatment in major depressive disorder (MDD) is a trial-and-error approach. Patients often have to undergo multiple medication trials for weeks to months before finding an effective treatment. Clinical factors such as severity of baseline symptoms and the presence of specific individual (anhedonia or insomnia) or cluster (atypical, melancholic, or anxious) of symptoms are commonly used without any evidence of their utility in selecting among currently available antidepressants. Read More

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http://dx.doi.org/10.1007/164_2018_171DOI Listing
October 2018
1 Read

Treatment of Depression in Women.

Handb Exp Pharmacol 2018 Oct 20. Epub 2018 Oct 20.

Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, CA, USA.

Women are more likely than men to experience depression throughout the life span. Sex differences in neurochemistry and brain structure, as well as societal factors may contribute to women's increased likelihood of depression. Pharmacological research targeting depression has historically excluded women, leading to a knowledge gap regarding effective antidepressant treatment in women. Read More

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http://dx.doi.org/10.1007/164_2018_163DOI Listing
October 2018
1 Read

Clinical Sleep-Wake Disorders I: Focus on Hypersomnias and Movement Disorders During Sleep.

Handb Exp Pharmacol 2018 Oct 20. Epub 2018 Oct 20.

Department of Neurology, University Hospital Zurich, University of Zurich, Zürich, Switzerland.

Central disorders of hypersomnolence are characterized by daily periods of irrepressible need to sleep or daytime lapses into sleep, as defined in the current version of the International Criteria of Sleep Disorders. Thus, the unifying symptom is excessive daytime sleepiness which is not caused by any other sleep-wake disorder. Relevant disorders including narcolepsy type 1 and 2, idiopathic hypersomnia, Kleine-Levin syndrome, and insufficient sleep syndrome will be discussed. Read More

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http://link.springer.com/10.1007/164_2018_126
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http://dx.doi.org/10.1007/164_2018_126DOI Listing
October 2018
12 Reads

In Vitro Models for Study of Brown Adipocyte Biology.

Authors:
Mark Christian

Handb Exp Pharmacol 2018 Oct 20. Epub 2018 Oct 20.

Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK.

Brown adipocytes are the key cell type in brown adipose tissue (BAT) that express the genes required for heat production through the process of thermogenesis. Brown adipocyte cell culture models are important for researching the molecular pathways that control cell autonomous processes. In vitro tools for the study of brown adipocytes include BAT explant cultures and BAT primary cultures that are first proliferated and then differentiated. Read More

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http://dx.doi.org/10.1007/164_2018_122DOI Listing
October 2018

Targeting DNA Repair.

Handb Exp Pharmacol 2018 ;249:161-180

Early Drug Development for Innovative Therapy Division, European Institute of Oncology, Via Ripamonti, 435 20141, Milan, Italy.

Genomic instability is a characteristic of most human cancers and plays critical roles in both cancer development and progression. There are various forms of genomic instability arising from many different pathways, such as DNA damage from endogenous and exogenous sources, centrosome amplification, telomere damage, and epigenetic modifications. DNA-repair pathways can enable tumor cells to survive DNA damage. Read More

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http://link.springer.com/10.1007/164_2017_31
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http://dx.doi.org/10.1007/164_2017_31DOI Listing
January 2018
9 Reads

Neurostimulation Therapies.

Handb Exp Pharmacol 2018 Oct 8. Epub 2018 Oct 8.

Washington University School of Medicine, St. Louis, MO, USA.

Depression is one of the most disabling conditions in the world. In many cases patients continue to suffer with depressive disorders despite a series of adequate trials of medication and psychotherapy. Neuromodulation treatments offer a qualitatively different modality of treatment that can frequently prove efficacious in these treatment-refractory patients. Read More

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http://link.springer.com/10.1007/164_2018_157
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http://dx.doi.org/10.1007/164_2018_157DOI Listing
October 2018
3 Reads

Use of Antidepressants in Patients with Co-occurring Depression and Substance Use Disorders.

Authors:
Theadia L Carey

Handb Exp Pharmacol 2018 Sep 23. Epub 2018 Sep 23.

Psychiatry Residency Training Director, Authority Health GME (General Medical Education), Community Faculty, Michigan State University, Detroit, MI, USA.

This chapter reviews antidepressant treatment considerations and recommendations for patients with co-occurring depression and substance use disorders. Depression and substance use disorders are highly comorbid conditions. Substance use disorders are chronic disorders that result in a cluster of symptoms indicating that an individual continues to use a substance despite significant problems resulting from their use. Read More

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http://dx.doi.org/10.1007/164_2018_162DOI Listing
September 2018
1 Read

Synthetic Opioids.

Handb Exp Pharmacol 2018 Sep 22. Epub 2018 Sep 22.

Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.

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. Read More

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http://dx.doi.org/10.1007/164_2018_149DOI Listing
September 2018
1 Read

Brown Adipose Tissue Development and Metabolism.

Handb Exp Pharmacol 2018 Sep 11. Epub 2018 Sep 11.

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.

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. Read More

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http://dx.doi.org/10.1007/164_2018_168DOI Listing
September 2018
3 Reads

Clinical Implications of the STAR*D Trial.

Handb Exp Pharmacol 2018 Sep 11. Epub 2018 Sep 11.

Deparment of Psychiatry, Texas Tech University-Health Sciences Center, Lubbock, TX, USA.

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. Read More

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http://dx.doi.org/10.1007/164_2018_153DOI Listing
September 2018

1,2-Diarylethylamine- and Ketamine-Based New Psychoactive Substances.

Handb Exp Pharmacol 2018 Sep 9. Epub 2018 Sep 9.

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.

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. Read More

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http://link.springer.com/10.1007/164_2018_148
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http://dx.doi.org/10.1007/164_2018_148DOI Listing
September 2018
25 Reads

Other Antidepressants.

Handb Exp Pharmacol 2018 Sep 8. Epub 2018 Sep 8.

Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine-Wichita, Wichita, KS, USA.

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. Read More

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http://dx.doi.org/10.1007/164_2018_167DOI Listing
September 2018
4 Reads

Therapeutic Drug Monitoring of Antidepressants.

Handb Exp Pharmacol 2018 Sep 8. Epub 2018 Sep 8.

Program in Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA.

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. Read More

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http://link.springer.com/10.1007/164_2018_161
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http://dx.doi.org/10.1007/164_2018_161DOI Listing
September 2018
14 Reads

Responding to New Psychoactive Substances in the European Union: Early Warning, Risk Assessment, and Control Measures.

Handb Exp Pharmacol 2018 Sep 8. Epub 2018 Sep 8.

European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal.

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. Read More

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http://dx.doi.org/10.1007/164_2018_160DOI Listing
September 2018
4 Reads

CGRP Receptor Signalling Pathways.

Handb Exp Pharmacol 2018 Aug 28. Epub 2018 Aug 28.

University of Reading, Reading, UK.

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. Read More

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http://dx.doi.org/10.1007/164_2018_130DOI Listing
August 2018
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Fatty Acid Metabolites as Novel Regulators of Non-shivering Thermogenesis.

Handb Exp Pharmacol 2018 Aug 24. Epub 2018 Aug 24.

Molecular Nutritional Medicine, Else Kröner-Fresenius Center for Nutritional Medicine, Technical University of Munich, Freising, Germany.

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. Read More

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http://link.springer.com/10.1007/164_2018_150
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http://dx.doi.org/10.1007/164_2018_150DOI Listing
August 2018
28 Reads

Aging of Brown and Beige/Brite Adipose Tissue.

Handb Exp Pharmacol 2018 Aug 24. Epub 2018 Aug 24.

Department of Adipocyte Development and Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.

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. Read More

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http://link.springer.com/10.1007/164_2018_151
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http://dx.doi.org/10.1007/164_2018_151DOI Listing
August 2018
15 Reads