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Handbook of Experimental Pharmacology

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https://www.readbyqxmd.com/read/30591968/regulation-of-inositol-biosynthesis-balancing-health-and-pathophysiology
#1
Kendall C Case, Michael Salsaa, Wenxi Yu, Miriam L Greenberg
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...
December 28, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30570691/drug-development-in-psychiatry-the-long-and-winding-road-from-chance-discovery-to-rational-development
#2
Sheldon H Preskorn
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...
December 21, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30570690/role-of-phospholipase-d-derived-phosphatidic-acid-in-regulated-exocytosis-and-neurological-disease
#3
Emeline Tanguy, Qili Wang, Nicolas Vitale
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...
December 21, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30535941/nop-ligands-for-the-treatment-of-anxiety-and-mood-disorders
#4
Elaine C Gavioli, Victor A D Holanda, Chiara Ruzza
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...
December 8, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30478737/exploring-the-therapeutic-landscape-of-sphingomyelinases
#5
Prajna Shanbhogue, Yusuf A Hannun
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)...
November 27, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30478736/regulatory-small-and-long-noncoding-rnas-in-brite-brown-adipose-tissue
#6
Marcel Scheideler
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. Therefore, the comprehensive understanding of the regulatory network in thermogenic adipocytes is in demand...
November 27, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30478735/self-experiments-with-psychoactive-substances-a-historical-perspective
#7
Torsten Passie, Simon D Brandt
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...
November 27, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30478734/nmda-antagonists-for-treatment-resistant-depression
#8
Nuri B Farber
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. A brief infusion of a low dose of this agent produces rapid improvement in depressive symptoms that lasts for several days. The improvement occurs after the agent has produced its well characterized psychotomimetic and cognitive side effects...
November 27, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30443786/functional-interactions-between-sleep-and-circadian-rhythms-in-learning-and-learning-disabilities
#9
H Craig Heller, Norman F Ruby
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. This chapter presents evidence that sleep and circadian rhythms do not just have separate influences on learning and memory that happen to coincide because of the circadian timing of sleep, but rather sleep and circadian systems have a critical functional interaction in the processes of memory consolidation...
November 16, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30443785/clinical-and-experimental-human-sleep-wake-pharmacogenetics
#10
Hans-Peter Landolt, Sebastian C Holst, Amandine Valomon
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...
November 16, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30443784/sleep-and-wake-like-states-in-small-networks-in-vivo-and-in-vitro
#11
Laura E McKillop, Vladyslav V Vyazovskiy
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...
November 16, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30430261/the-nociceptin-orphanin-fq-system-and-the-regulation-of-memory
#12
Lionel Moulédous
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. This review describes the consequences of the pharmacological manipulation of the N/OFQ system by NOP receptor ligands on learning processes and on the consolidation of various types of long-term memory...
November 15, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30430260/nociceptin-orphanin-fq-and-urinary-bladder
#13
Patrizia Angelico, Marco Barchielli, Massimo Lazzeri, Remo Guerrini, Girolamo Calò
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. Moreover daily treatment with intravesical N/OFQ for 10 days significantly reduced urine leakage episodes...
November 15, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30430259/cgrp-discovery-and-timeline
#14
Kate Arkless, Fulye Argunhan, Susan D Brain
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. Despite all, there is still much to learn concerning the relevance of the vasodilator and other activities as well as further potential applications of CGRP agonists and blockers in disease...
November 15, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30406443/neuropharmacology-of-synthetic-cathinones
#15
Michael H Baumann, Hailey M Walters, Marco Niello, Harald H Sitte
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.g., bupropion, Wellbutrin® ), while others are problematic drugs of abuse (e.g., 4-methylmethcathinone, mephedrone). Similar to amphetamines, synthetic cathinones are psychomotor stimulants that exert their effects by impairing the normal function of plasma membrane transporters for dopamine (DAT), norepinephrine (NET), and 5-HT (SERT)...
November 8, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30406442/cancer-evolution-as-the-new-frontier-of-precision-medicine
#16
Giuseppe Curigliano
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...
November 8, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30368652/role-of-inflammation-in-depression-and-treatment-implications
#17
Jennifer C Felger
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. Numerous studies (including meta-analyses) have found elevated peripheral and central inflammatory cytokines and acute phase proteins in depression...
October 28, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30367253/designer-benzodiazepines-another-class-of-new-psychoactive-substances
#18
Bjoern Moosmann, Volker Auwärter
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. Although being of great value as medicines, dependence to these drugs is a concern worldwide, in part due to overprescription and easy availability. Therefore, the phenomenon of benzodiazepines sold via Internet shops without restrictions at low prices is alarming and poses a serious threat to public health...
October 27, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30341727/pharmacogenomics-and-biomarkers-of-depression
#19
Manish K Jha, Madhukar H Trivedi
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...
October 20, 2018: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/30341726/treatment-of-depression-in-women
#20
Christina Bourne, Laura Kenkel
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. Antidepressant pharmacokinetics and pharmacodynamics are clearly different in men and women, necessitating a thoughtful approach to their prescription and management...
October 20, 2018: Handbook of Experimental Pharmacology
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