1,635 results match your criteria Handbook of Experimental Pharmacology [Journal]


Impact, Diagnosis, Phenomenology, and Biology.

Authors:
William Coryell

Handb Exp Pharmacol 2019 Apr 20. Epub 2019 Apr 20.

Department of Psychiatry, Carver College of Medicine, University of Iowa Health Care, Iowa City, IA, USA.

This section provides summaries of the epidemiology, phenomenology, nosology, and the suspected biological substrates of the depressive disorders. It particularly emphasizes the historical evolution of the pertinent diagnostic constructs and the prognostic import both of the various diagnostic groupings and of the individual symptoms and symptom clusters. Read More

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http://dx.doi.org/10.1007/164_2018_156DOI Listing

The Function(s) of Sleep.

Handb Exp Pharmacol 2019 Apr 20. Epub 2019 Apr 20.

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

Sleep is a highly conserved phenomenon in endotherms, and therefore it must serve at least one basic function across this wide range of species. What that function is remains one of the biggest mysteries in neurobiology. By using the word neurobiology, we do not mean to exclude possible non-neural functions of sleep, but it is difficult to imagine why the brain must be taken offline if the basic function of sleep did not involve the nervous system. Read More

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http://link.springer.com/10.1007/164_2018_140
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http://dx.doi.org/10.1007/164_2018_140DOI Listing
April 2019
3 Reads

Clinical Pharmacology and Pharmacometrics to Better Understand Physiological Changes During Pregnancy and Neonatal Life.

Handb Exp Pharmacol 2019 Apr 10. Epub 2019 Apr 10.

Pediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, Basel, Switzerland.

Pregnant women, fetuses, and newborns are particularly vulnerable patient populations. During pregnancy, the body is subject to physiological changes that influence the pharmacokinetics and pharmacodynamics of drugs. Inappropriate dosing in pregnant women can result in sub-therapeutic or toxic effects, putting not only the pregnant woman but also her fetus at risk. Read More

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http://dx.doi.org/10.1007/164_2019_210DOI Listing

NOP-Related Mechanisms in Substance Use Disorders.

Handb Exp Pharmacol 2019 Apr 10. Epub 2019 Apr 10.

Department of Neuroscience, The Scripps Research Institute, La Jolla, CA, USA.

Nociceptin/orphanin FQ (N/OFQ) is a 17 amino acid peptide that was deorphanized in 1995 and has been widely studied since. The role of the N/OFQ system in drug abuse has attracted researchers' attention since its initial discovery. The first two scientific papers describing the effect of intracranial injection of N/OFQ appeared 20 years ago and reported efficacy of the peptide in attenuating alcohol intake, whereas heroin self-administration was insensitive. Read More

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http://dx.doi.org/10.1007/164_2019_209DOI Listing
April 2019
1 Read

Cebranopadol: A Novel First-in-Class Potent Analgesic Acting via NOP and Opioid Receptors.

Handb Exp Pharmacol 2019 Mar 30. Epub 2019 Mar 30.

Grünenthal GmbH, Global Innovation, Aachen, Germany.

Cebranopadol is a novel first-in-class analgesic with highly potent agonistic activity at nociceptin/orphanin FQ peptide (NOP) and opioid receptors. It is highly potent and efficacious across a broad range of preclinical pain models. Its side effect profile is better compared to typical opioids. Read More

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http://dx.doi.org/10.1007/164_2019_206DOI Listing
March 2019
2 Reads

Effects of NOP-Related Ligands in Nonhuman Primates.

Handb Exp Pharmacol 2019 Mar 17. Epub 2019 Mar 17.

Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

The nociceptin/orphanin FQ peptide (NOP) receptor-related ligands have been demonstrated in preclinical studies for several therapeutic applications. This article highlights (1) how nonhuman primates (NHP) were used to facilitate the development and application of positron emission tomography tracers in humans; (2) effects of an endogenous NOP ligand, nociceptin/orphanin FQ, and its interaction with mu opioid peptide (MOP) receptor agonists; and (3) promising functional profiles of NOP-related agonists in NHP as analgesics and treatment for substance use disorders. NHP models offer the most phylogenetically appropriate evaluation of opioid and non-opioid receptor functions and drug effects. Read More

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http://link.springer.com/10.1007/164_2019_211
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http://dx.doi.org/10.1007/164_2019_211DOI Listing
March 2019
17 Reads

Narcotic-Sparing Approaches and the Shift Toward Paracetamol in Neonatal Intensive Care.

Handb Exp Pharmacol 2019 Mar 17. Epub 2019 Mar 17.

Intensive Care, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

Effective analgesia in neonates is relevant not only because of ethical aspects or empathy, but it is a crucial and integral part of medical and nursing care. However, there is also emerging evidence - although mainly in animal models - on the relation between the exposure to narcotics and impaired neurodevelopmental outcome, resulting in a CATCH-22 scenario. Consequently, a balanced approach is needed with the overarching intention to attain adequate pain management with minimal side effects. Read More

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http://dx.doi.org/10.1007/164_2019_207DOI Listing

Understanding CGRP and Cardiovascular Risk.

Handb Exp Pharmacol 2019 Mar 17. Epub 2019 Mar 17.

Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

Increasing knowledge about the role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology has led to the development of antibodies against this peptide or its receptor. However, CGRP is widely expressed throughout the body, participating not only in pathophysiological conditions but also in several physiological processes and homeostatic responses during pathophysiological events. Therefore, in this chapter, the risks of long-term blockade of the CGRP pathway will be discussed, with focus on the cardiovascular system, as this peptide has been described to have a protective role during ischemic events, and migraine patients present a higher risk of stroke and myocardial infarction. Read More

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http://dx.doi.org/10.1007/164_2019_204DOI Listing

Electrophysiological Actions of N/OFQ.

Handb Exp Pharmacol 2019 Mar 6. Epub 2019 Mar 6.

Pain Management Research Institute, Kolling Institute of Medical Research, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney and Royal North Shore Hospital, St Leonards, NSW, Australia.

Whilst the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) has similar intracellular coupling mechanisms to opioid receptors, it has distinct modulatory effects on physiological functions such as pain. These actions range from agonistic to antagonistic interactions with classical opioids within the spinal cord and brain, respectively. Understanding the electrophysiological actions of N/OFQ has been crucial in ascertaining the mechanisms by which these agonistic and antagonistic interactions occur. Read More

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http://dx.doi.org/10.1007/164_2019_205DOI Listing
March 2019
1 Read

Selective Serotonin Reuptake Inhibitors.

Handb Exp Pharmacol 2019 Mar 6. Epub 2019 Mar 6.

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

The first antidepressants were created by chance but brought the idea that central serotonin agonism produced an antidepressant effect. SSRIs were the first class of psychotropic medications to be rationally designed, meaning that researchers intended to utilize a specific mechanism of action while avoiding adverse effects. In this way, SSRIs were created to be safer and more tolerable than previous antidepressants. Read More

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http://dx.doi.org/10.1007/164_2018_172DOI Listing
March 2019
1 Read

Serotonin and Norepinephrine Reuptake Inhibitors.

Handb Exp Pharmacol 2019 Mar 6. Epub 2019 Mar 6.

University of Alabama at Birmingham, Birmingham, AL, USA.

This chapter covers antidepressants that fall into the class of serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors. That is, they bind to the 5-HT and NE transporters with varying levels of potency and binding affinity ratios. Unlike the selective serotonin (5-HT) reuptake inhibitors (SSRIs), most of these antidepressants have an ascending rather than a flat dose-response curve. Read More

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http://dx.doi.org/10.1007/164_2018_164DOI Listing
March 2019
9 Reads

Correction to: Transcriptional Regulators as Targets for Alcohol Pharmacotherapies.

Handb Exp Pharmacol 2018 ;248:623-624

Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.

Figure 1 was published incorrectly in this chapter. The original chapter was corrected. Read More

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http://dx.doi.org/10.1007/164_2018_194DOI Listing
January 2018

Correction to: Innate Immune Signaling and Alcohol Use Disorders.

Handb Exp Pharmacol 2018 ;248:621

Bowles Center for Alcohol Studies, Department of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.

In the second paragraph of section 1.3 on line 27, the text appears incorrect as glutamatergic and neurons. It should read as glutamatergic and GABAergic neurons. Read More

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http://dx.doi.org/10.1007/164_2018_193DOI Listing
January 2018

Correction to: Advancing Pharmacotherapy Development from Preclinical Animal Studies.

Authors:
Mark Egli

Handb Exp Pharmacol 2018 ;248:625

Division of Neuroscience and Behavior, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.

In the 7th line from the bottom of the Abstract the word nociception appears incorrect. Read More

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http://dx.doi.org/10.1007/164_2018_191DOI Listing
January 2018
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Correction to: Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations and Drinking Behavior.

Handb Exp Pharmacol 2018 ;248:619

Departments of Neuroscience and Psychiatry and Behavioral Sciences, Charleston Alcohol Research Center, Addiction Sciences Division, Medical University of South Carolina, Charleston, SC, USA.

In section 8.1 on the 10 line in first paragraph the reference citation Mateos-Aparicio et al. 2014 is incorrect. Read More

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http://dx.doi.org/10.1007/164_2018_192DOI Listing
January 2018

Correction to: GABA Receptor Subtype Mechanisms and the Abuse-Related Effects of Ethanol: Genetic and Pharmacological Evidence.

Handb Exp Pharmacol 2018 ;248:615

Graduate Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA.

The chemical name appearing in the first column of Table 1 on the 3 row from bottom of the table is wrong. Read More

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http://dx.doi.org/10.1007/164_2018_190DOI Listing
January 2018
2 Reads

Correction to: Presynaptic Ethanol Actions: Potential Roles in Ethanol Seeking.

Authors:
David M Lovinger

Handb Exp Pharmacol 2018 ;248:617

Laboratory for Integrative Neuroscience, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.

The Acknowledgements unfortunately went missing to be included in the chapter. Read More

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http://link.springer.com/10.1007/164_2018_189
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http://dx.doi.org/10.1007/164_2018_189DOI Listing
January 2018
7 Reads

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
5 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
1 Read

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
2 Reads

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
2 Reads

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 ;251:381-424

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
2 Reads

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
1 Read

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
1 Read

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
1 Read

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
6 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
5 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
1 Read

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
1 Read

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
10 Reads

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

Handb Exp Pharmacol 2019 ;251:215-237

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
January 2019
10 Reads

Self-Experiments with Psychoactive Substances: A Historical Perspective.

Handb Exp Pharmacol 2018;252:69-110

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
January 2018
4 Reads

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
1 Read

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
15 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
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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
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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
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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
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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
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Neuropharmacology of Synthetic Cathinones.

Handb Exp Pharmacol 2018;252:113-142

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
January 2018
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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
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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
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Designer Benzodiazepines: Another Class of New Psychoactive Substances.

Handb Exp Pharmacol 2018;252:383-410

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
January 2018
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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
3 Reads