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Handbook of Experimental Pharmacology

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
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
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
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
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
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
Christian R Baumann
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. Other central disorders of hypersomnolence include hypersomnias due to medical or psychiatric disorders or because of medication or substance use...
October 20, 2018: Handbook of Experimental Pharmacology
Mark Christian
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. A number of stable brown preadipocyte cell lines have been generated by the expression transforming factors such as SV40 T antigen...
October 20, 2018: Handbook of Experimental Pharmacology
Giuseppe Curigliano
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. The failure to respond to DNA damage is a characteristic associated with genomic instability. Understanding of genomic instability in cancer is still very limited, but the further understanding of the molecular mechanisms through which the DNA damage response (DDR) operates, in combination with the elucidation of the genetic interactions between DDR pathways and other cell pathways, will provide therapeutic opportunities for the personalized medicine of cancer...
October 20, 2018: Handbook of Experimental Pharmacology
Nicholas T Trapp, Willa Xiong, Charles R Conway
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. The field of neuromodulation focuses on the use of electrical/electromagnetic energy, both invasively and noninvasively, to interface with and ultimately alter activity within the human brain for therapeutic purposes...
October 8, 2018: Handbook of Experimental Pharmacology
J Craig Nelson
Depression is a common disorder in late life that is associated with poor quality of life, increased disability, and increased all-cause mortality. Rates of completed suicide are the highest in older depressed men compared with any other age group. In this age group, depression is often concurrent with medical illness and it can aggravate the course of medical illness. Cognitive impairment is frequently present and may be the result of the depression itself or may be the consequence of a neurodegenerative disorder such as Alzheimer's disease...
October 8, 2018: Handbook of Experimental Pharmacology
Theadia L Carey
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. About 17 million Americans have an alcohol use disorder, and another approximately 7 million individuals have other drug use disorders (not including alcohol) in the United States...
September 23, 2018: Handbook of Experimental Pharmacology
Patrick M Beardsley, Yan Zhang
Opioid abuse has been a global menace for centuries, but the proliferation of synthetic opioids and their use within this current decade have created epidemic-level harms in some countries. According to the United Nations Office on Drugs and Crime, almost 12 million years were estimated loss of "healthy" life resulting in premature death and disability attributable to global opioid abuse just in 2015. Law enforcement and regulatory authorities have been particularly challenged abating the spread of synthetic opioids because soon after controlling the currently recognized abused opioids, their structures are tweaked, and new entities replace them...
September 22, 2018: Handbook of Experimental Pharmacology
Su Myung Jung, Joan Sanchez-Gurmaches, David A Guertin
Brown adipose tissue is well known to be a thermoregulatory organ particularly important in small rodents and human infants, but it was only recently that its existence and significance to metabolic fitness in adult humans have been widely realized. The ability of active brown fat to expend high amounts of energy has raised interest in stimulating thermogenesis therapeutically to treat metabolic diseases related to obesity and type 2 diabetes. In parallel, there has been a surge of research aimed at understanding the biology of rodent and human brown fat development, its remarkable metabolic properties, and the phenomenon of white fat browning, in which white adipocytes can be converted into brown like adipocytes with similar thermogenic properties...
September 11, 2018: Handbook of Experimental Pharmacology
A John Rush, Shailesh Bobby Jain
This chapter provides a synopsis of the clinically relevant findings derived from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and selected ancillary studies appended to the primary trial. The chapter describes the participants, their recruitment and treatment, and the study design, primary outcomes, and clinically informative results. In particular, the chapter describes acute phase response and remission rates from each of the five treatment steps which entail antidepressant monotherapies and combinations, and psychotherapy alone or in combination with an antidepressant...
September 11, 2018: Handbook of Experimental Pharmacology
Jason Wallach, Simon D Brandt
While phencyclidine (PCP) and ketamine remain the most well-studied and widely known dissociative drugs, a number of other agents have appeared since the late 1950s and early 1960s, when the pharmacological potential of this class was first realized. For example, hundreds of compounds have been pursued as part of legitimate research efforts to explore these agents. Some of these found their way out of the research labs and onto illicit markets of the 1960s and following decades as PCP analogs. Other "illicit analogs" apparently never appeared in the scientific literature prior to their existence on clandestine markets, thus originating as novel innovations in the minds of clandestine chemists and their colleagues...
September 9, 2018: Handbook of Experimental Pharmacology
T E Schwasinger-Schmidt, M Macaluso
This chapter addresses the following FDA-approved medications for the treatment of major depressive disorder available for use in the United States including bupropion, mirtazapine, trazodone, vortioxetine, and vilazodone. These medications do not belong to one of the previously featured classes of antidepressants discussed in the preceding chapters. Each medication featured in this chapter has a unique structure and properties that target diverse receptors in the central nervous system. These diverse targets are distinct from other classes of medications used to treat major depressive disorder...
September 8, 2018: Handbook of Experimental Pharmacology
Najla Fiaturi, David J Greenblatt
For a number of antidepressants in current clinical use, concentrations in serum or plasma are a more reliable index of target drug concentrations than is dosage. For such drugs, therapeutic drug monitoring (TDM) may be a useful clinical guide for the purpose of maximizing the likelihood of favorable therapeutic outcome while minimizing the probability of clinical ineffectiveness or adverse side effects. TDM is of greatest benefit when a therapeutic range of serum concentrations has been well established. Even if such a range is not definitively determined, TDM can be of help in situations in which patients are refractory to therapy despite adequate or high dosages, when adverse events supervene even with low doses, or when noncompliance with the intended dosage plan is suspected...
September 8, 2018: Handbook of Experimental Pharmacology
Michael Evans-Brown, Roumen Sedefov
New psychoactive substances (NPS) are drugs that are not controlled by the United Nations international drug control conventions of 1961 and 1971 but that may pose similar threats to public health. Many of them are traded as "legal" replacements to controlled drugs such as cannabis, heroin, benzodiazepines, cocaine, amphetamines, and 3,4-methylenedioxymethamphetamine (MDMA). Driven by globalization, there has been a large increase in the availability and, subsequently, harms caused by these substances over the last decade in Europe...
September 8, 2018: Handbook of Experimental Pharmacology
Graeme S Cottrell
Calcitonin gene-related peptide (CGRP) is a promiscuous peptide, similar to many other members of the calcitonin family of peptides. The potential of CGRP to act on many different receptors with differing affinities and efficacies makes deciphering the signalling from the CGRP receptor a challenging task for researchers.Although it is not a typical G protein-coupled receptor (GPCR), in that it is composed not just of a GPCR, the CGRP receptor activates many of the same signalling pathways common for other GPCRs...
August 28, 2018: Handbook of Experimental Pharmacology
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