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Handbook of Experimental Pharmacology

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https://read.qxmd.com/read/31004226/impact-diagnosis-phenomenology-and-biology
#1
William Coryell
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.
April 20, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/31004225/the-function-s-of-sleep
#2
Marcos G Frank, H Craig Heller
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. In this chapter we discuss several current hypotheses about sleep function...
April 20, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30968215/clinical-pharmacology-and-pharmacometrics-to-better-understand-physiological-changes-during-pregnancy-and-neonatal-life
#3
Tamara van Donge, Katrina Evers, Gilbert Koch, John van den Anker, Marc Pfister
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. During neonatal life, maturation processes also affect pharmacokinetics and pharmacodynamics of drugs. Inappropriate dosing in newborns leads not only to short-term complications but can also have a negative impact on the long-term development of infants and children...
April 10, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30968214/nop-related-mechanisms-in-substance-use-disorders
#4
Roberto Ciccocioppo, Anna Maria Borruto, Ana Domi, Koji Teshima, Nazzareno Cannella, Friedbert Weiss
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. Since then more than 100 scientific articles investigating the role of the N/OFQ and N/OFQ receptor (NOP) system in drug abuse have been published...
April 10, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30927089/cebranopadol-a-novel-first-in-class-potent-analgesic-acting-via-nop-and-opioid-receptors
#5
Thomas M Tzschentke, Klaus Linz, Thomas Koch, Thomas Christoph
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. Mechanistic studies have shown that cebranopadol's activity at NOP receptors contributes to its anti-hyperalgesic effects while ameliorating some of its opioid-type side effects, including respiratory depression and abuse potential...
March 30, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30879202/effects-of-nop-related-ligands-in-nonhuman-primates
#6
Norikazu Kiguchi, Mei-Chuan Ko
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...
March 17, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30879201/narcotic-sparing-approaches-and-the-shift-toward-paracetamol-in-neonatal-intensive-care
#7
Karel Allegaert, Dick Tibboel, John van den Anker
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. Despite the available evidence-based guidance on narcotics in ventilated neonates, observations on drug utilization still suggest an overall increase in exposure with extensive variability between units...
March 17, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30879200/understanding-cgrp-and-cardiovascular-risk
#8
Eloísa Rubio-Beltrán, Antoinette Maassen van den Brink
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...
March 17, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30838458/electrophysiological-actions-of-n-ofq
#9
Bryony L Winters, Macdonald J Christie, Christopher W Vaughan
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. These similarities and differences between N/OFQ and opioids are due to the relative location of NOP versus opioid receptors on specific neuronal elements within these CNS regions...
March 6, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30838457/selective-serotonin-reuptake-inhibitors
#10
Dee Lochmann, Tara Richardson
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. SSRIs share many similarities, but differ in terms of pharmacokinetics and effects on CYP450 enzymes, which is detailed in this chapter...
March 6, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30838456/serotonin-and-norepinephrine-reuptake-inhibitors
#11
Richard C Shelton
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. The chapter provides a brief review of the chemistry, pharmacology, metabolism, safety and adverse effects, clinical use, and therapeutic indications of each antidepressant...
March 6, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30771012/n-ofq-nop-system-in-peripheral-and-central-immunomodulation
#12
Salim Kadhim, Mark F Bird, David G Lambert
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., neuropathic pain. Nociceptin/Orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ peptide receptor, NOP; peripheral and central activation can modulate immune function. In the periphery, NOP activation generally depresses immune function, but unlike classical opioids this is in part driven by NOP located on circulating immune cells...
February 16, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30725285/n-ofq-nop-system-and-airways
#13
Bruno D'Agostino, Manuela Sgambato, Renata Esposito, Giuseppe Spaziano
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. Nociceptin/OFQ-NOP receptor system is able to combine anti-hyperresponsiveness and immunomodulatory actions. In particular, N/OFQ is able to inhibit airways microvascular leakage and bronchoconstriction through a presynaptic and non-opioid mechanism of action that blocks tachykinin release...
February 7, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30725284/pharmacological-assays-for-investigating-the-nop-receptor
#14
Davide Malfacini, Girolamo Calo'
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. Here, we review the in vitro methodologies employed, which have contributed to our understanding of this target...
February 7, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30725283/role-of-cgrp-in-migraine
#15
Lars Edvinsson
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...
February 7, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30701317/therapeutic-approaches-for-nop-receptor-antagonists-in-neurobehavioral-disorders-clinical-studies-in-major-depressive-disorder-and-alcohol-use-disorder-with-btrx-246040-ly2940094
#16
Jeffrey M Witkin, Tanya L Wallace, William J Martin
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...
January 31, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30810864/correction-to-transcriptional-regulators-as-targets-for-alcohol-pharmacotherapies
#17
Antonia M Savarese, Amy W Lasek
Figure 1 was published incorrectly in this chapter. The original chapter was corrected. The correct Figure 1 is.
January 29, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30810863/correction-to-innate-immune-signaling-and-alcohol-use-disorders
#18
Leon G Coleman, Fulton T Crews
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. The original chapter was corrected.
January 29, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30810862/correction-to-advancing-pharmacotherapy-development-from-preclinical-animal-studies
#19
Mark Egli
In the 7th line from the bottom of the Abstract the word nociception appears incorrect. It should read nocioceptin. In section 3.4 on the third line of 2nd paragraph the word nociception appears incorrect. It should read nocioceptin. The original chapter was corrected.
January 29, 2019: Handbook of Experimental Pharmacology
https://read.qxmd.com/read/30689091/nop-targeted-peptide-ligands
#20
Delia Preti, Girolamo Calo', Remo Guerrini
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...
January 29, 2019: Handbook of Experimental Pharmacology
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