International Union of Basic and Clinical Pharmacology. CVIII. Calcium-Sensing Receptor Nomenclature, Pharmacology, and Function.
Osborne H Abstract The calcium-sensing receptor (CaSR) is a class C G protein-coupled receptor that responds to multiple endogenous agonists and allosteric modulators, including divalent and trivalent cations, L-amino acids, γ-glutamyl peptides, polyamines, polycationic peptides, and protons. The CaSR plays a critical role in extracellular calcium (Ca2+ o) homeostasis, as demonstrated by the many naturally occurring mutations in the CaSR or its signaling partners that cause Ca2+ o homeostasis disorders. However, CaSR tissue expression in mammals is broad and includes tissues unrelated to Ca2+ o homeostasis, ...
Source: Pharmacological Reviews - May 31, 2020 Category: Drugs & Pharmacology Authors: Leach K, Hannan FM, Josephs TM, Keller AN, Møller TC, Ward DT, Kallay E, Mason RS, Thakker RV, Riccardi D, Conigrave AD, Bräuner-Osborne H Tags: Pharmacol Rev Source Type: research

Anti-nerve growth factor antibodies for the treatment of low back pain.
Abstract INTRODUCTION: The treatment of chronic low back pain (cLBP) often involves multimodal pharmacologic and non-pharmacologic strategies. There remain shortcomings with these tools with regards to both effect size and side effects. AREAS COVERED: In an effort to better address cLBP, anti-nerve growth factor (NGF) monoclonal antibodies (mAbs) are nearing marketing approval. This class of medications has been primarily evaluated for osteoarthritis, but are being examined at higher doses for use in cLBP. We review the efficacy of this class in treating LBP as well as their potential side effects based on ni...
Source: Pharmacological Reviews - May 21, 2020 Category: Drugs & Pharmacology Authors: Patel F, Hess DK, Maher DP Tags: Expert Rev Clin Pharmacol Source Type: research

Glucocorticoids in rheumatoid arthritis: the silent companion in the therapeutic strategy.
Abstract INTRODUCTION: Glucocorticoids (GCs) are key actors in RA management, despite the increasing number of available drugs. In fact, due to their efficacy and safety, the combination therapy between GCs and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is still recommended in the early phase of RA treatment, because improving the long-term results. AREAS COVERED: In this paper, we reviewed the role of GCs in RA management, focusing on mechanisms of action as well as the benefit/risk ratio of GCs and newer therapeutic formulations. Furthermore, we analysed GCs DMARDs proprieties ...
Source: Pharmacological Reviews - May 20, 2020 Category: Drugs & Pharmacology Authors: Berardicurti O, Ruscitti P, Pavlych V, Conforti A, Giacomelli R, Cipriani P Tags: Expert Rev Clin Pharmacol Source Type: research

Residual risk reduction opportunities in patients with chronic coronary syndrome. Role of Dual Pathway Inhibition.
e;ndez JL, Lozano FS, Suarez Fernández C Abstract INTRODUCTION: In this review, the role of the rivaroxaban-plus-aspirin approach (dual pathway inhibition - DPI) in patients with chronic coronary syndrome (CCS) and to perform practical recommendations about its use was updated. AREAS COVERED: The contents of this review were proposed in an expert meeting. To identify relevant articles, a systematic search of Medline/Embase was performed (to July 2019), using the key words "rivaroxaban", "vascular dose", "COMPASS" and "coronary artery disease" in the search strate...
Source: Pharmacological Reviews - May 20, 2020 Category: Drugs & Pharmacology Authors: González-Juanatey JR, Almendro-Delia M, Cosín-Sales J, Bellmunt-Montoya S, Gómez-Doblas JJ, Riambau V, García-Moll X, García-Alegría J, Hernández JL, Lozano FS, Suarez Fernández C Tags: Expert Rev Clin Pharmacol Source Type: research

Immunogenicity - unwanted immune responses to biological drugs - can we predict them?
Abstract INTRODUCTION: . Biological agents (BAs) target molecules involved in disease mechanisms and have modified the natural history of several immune-mediated disorders. All BAs are immunogenic, resulting in the formation of antidrug antibodies (ADAs), which can neutralize drug activity leading to loss of response and potential relapse, or serious adverse events such as infusion hypersensitivity reactions. The production of ADAs is the result of a specific adaptive immune response in which T and B cells are involved. AREAS COVERED: . Factors conditioning the immunogenicity of BAs, including drug-, treatmen...
Source: Pharmacological Reviews - May 20, 2020 Category: Drugs & Pharmacology Authors: Andrea M, Francesca N, Emanuele V, Susanna B, Enrico M, Alessandra V Tags: Expert Rev Clin Pharmacol Source Type: research

The pharmacology of antibiotic therapy in Hidradenitis Suppurativa.
In this study, we have reviewed the available antibiotic therapies for HS, analyzing the pharmacologic aspects of these kind of treatments.Areas covered: The role of bacteria, infections and superinfections in HS is still debated and controversial. Antibiotics are recognized as first-line treatments for hidradenitis suppurativa, but the data on their efficacy are limited. Antibiotics should not be replaced by new biological therapies and it is not necessary to make an efficacy classification: it is important for dermatologists to recognize the right patient and the right moment to prescribe an antibiotic therapy, together ...
Source: Pharmacological Reviews - May 4, 2020 Category: Drugs & Pharmacology Authors: Marasca C, Tranchini P, Marino V, Annunziata MC, Napolitano M, Fattore D, Fabbrocini G Tags: Expert Rev Clin Pharmacol Source Type: research

Strategies for recombinant production of antimicrobial peptides with pharmacological potential.
Abstract Introduction: The need to develop new drugs for the control of pathogenic microorganisms has redoubled efforts to prospect for antimicrobial peptides (AMPs) from natural sources and to characterize its structure and function. These molecules present a broad spectrum of action against different microorganisms and frequently present promiscuous action, with anticancer and immunomodulatory activities. Furthermore, AMPs can be used as biopharmaceuticals in the treatment of hospital-acquired infections and other serious diseases with relevant social and economic impacts.Areas covered: The low yield and the the...
Source: Pharmacological Reviews - May 1, 2020 Category: Drugs & Pharmacology Authors: Sampaio de Oliveira KB, Leite ML, Rodrigues GR, Duque HM, Costa RA, Cunha VA, de Loiola Costa LS, da Cunha NB, Franco OL, Dias SC Tags: Expert Rev Clin Pharmacol Source Type: research

Translating the statistical benefits of SGLT-2 inhibitors on Cardio-renal outcomes into clinical practice.
This study aims to analyze the positive outcomes observed in cardiovascular outcomes trials conducted with sodium glucose co-transporter inhibitors and determine their statistical and clinical significance.Methods: A literature search conducted using the Cochrane library resulted in five citations - randomized controlled trials (RCTs), identified for analysis. Positive cardio-renal outcomes from the 5 RCTs were analyzed in accordance with a pre-defined strategy which included the hierarchical flow chart, presence of a persuasive p-value (p
Source: Pharmacological Reviews - April 22, 2020 Category: Drugs & Pharmacology Authors: Ghosal S, Sinha B Tags: Expert Rev Clin Pharmacol Source Type: research

Prognostic factors of good response to DMARDs in psoriatic arthritis: a narrative review.
Abstract Introduction: The management of Psoriatic arthritis (PsA) has evolved in the last decade with a significant increase in treatment options making the choice for clinicians difficult. Thus, the different factors of good prognosis for each treatment are presented in this review.Areas covered: Current available treatment and assessment tools for the response of treatment are presented. A systematic review of the literature, on Pubmed, Medline and Cochrane databases and abstracts from the last three EULAR and ACR annual conferences was performed. Factors associated with a good response to csDMARDs, tsDMARDs an...
Source: Pharmacological Reviews - April 20, 2020 Category: Drugs & Pharmacology Authors: Mekhail C, Chouk M, Prati C, Wendling D, Verhoeven F Tags: Expert Rev Clin Pharmacol Source Type: research

Pharmacologic management of Mycobacterium ulcerans infection.
Abstract Introduction: Pharmacological treatment of Buruli ulcer (Mycobacterium ulcerans infection; BU) is highly effective, as shown in two randomized trials in Africa.Areas covered: We review BU drug treatment - in vitro, in vivo and clinical trials (PubMed: '(Buruli OR (Mycobacterium AND ulcerans)) AND (treatment OR therapy).' We also highlight the pathogenesis of M. ulcerans infection that is dominated by mycolactone, a secreted exotoxin, that causes skin and soft tissue necrosis, and impaired immune response and tissue repair. Healing is slow, due to the delayed wash-out of mycolactone. An array of repurpo...
Source: Pharmacological Reviews - April 20, 2020 Category: Drugs & Pharmacology Authors: Van Der Werf TS, Barogui YT, Converse PJ, Phillips RO, Stienstra Y Tags: Expert Rev Clin Pharmacol Source Type: research

Can the microbiota predict response to systemic cancer therapy, surgical outcomes, and survival? The answer is in the gut.
Abstract Introduction: The gut microbiota seems to play a key role in tumorigenesis, across various hallmarks of cancer. Recent evidence suggests its potential use as a biomarker predicting drug response and adding prognostic information, generally in the context of immuno-oncology.Areas covered: In this review we focus on the modulating effects of gut-microbiota dysbiosis on various anticancer molecules used in practice, including cytotoxic and immune-modulating agents, primarily immune-checkpoint inhibitors (ICI). Pubmed/Medline-based literature search was conducted to find potential original studies that discus...
Source: Pharmacological Reviews - April 18, 2020 Category: Drugs & Pharmacology Authors: El Bairi K, Jabi R, Trapani D, Boutallaka H, Ouled Amar Bencheikh B, Bouziane M, Amrani M, Afqir S, Maleb A Tags: Expert Rev Clin Pharmacol Source Type: research

Ginsenoside-Rb1 for Ischemic Stroke: A Systematic Review and Meta-analysis of Preclinical Evidence and Possible Mechanisms.
Abstract Background: Ischemic stroke is the most common type of stroke, while pharmacological therapy options are limited. Ginsenosides are the major bioactive compounds in Ginseng and have been found to have various pharmacological effects in the nervous system. In the present study, we sought to evaluate the effects of Ginsenoside-Rb1 (G-Rb1), an important ingredient of ginsenosides, and the probable neuroprotective mechanisms in experimental ischemic strokes. Methods: Studies of G-Rb1 on ischemic stroke animal models were identified from 7 databases. No clinical trials were included in the analysis. The pr...
Source: Pharmacological Reviews - April 17, 2020 Category: Drugs & Pharmacology Authors: Shi YH, Li Y, Wang Y, Xu Z, Fu H, Zheng GQ Tags: Front Pharmacol Source Type: research

The effect of tramadol on blood glucose concentrations: a systematic review.
Abstract Introduction: tramadol is a synthetic opioid whose consumption is growing worldwide. In addition to the common side effects of this medication, blood glucose impairment is another important adverse effect. Nevertheless, studies comprehensively summarizing the impact of tramadol use on glucose homeostasis are very sparse. Thus, the present study was performed to collect and summarize the latest information about this issue in a systematic way.Areas covered: An exhaustive literature search was carried out using relevant keywords. Web of Sciences, PubMed, Scopus, and Google scholar were interrogated until 30...
Source: Pharmacological Reviews - April 15, 2020 Category: Drugs & Pharmacology Authors: Nakhaee S, Brent J, Hoyte C, Farrokhfall K, Shirazi M, Askari M, Mehrpour O Tags: Expert Rev Clin Pharmacol Source Type: research

Pathophysiology, diagnosis and pharmacological treatment of gastro-esophageal reflux disease.
Abstract Introduction: Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic, relapsing disorder, whose knowledge has increased in last years thanks to the advent of new sophisticated techniques, such as 24-hour impedance-pH monitoring and high-resolution manometry, for the study of esophageal functions.Areas covered: This review provides an overview of our advancements in understanding the complex pathophysiology, improving the diagnosis and defining the modern pharmacological therapeutic approach to GERD.Expert opinion: The growing clinical application of impedance-pH testing has allowed us to k...
Source: Pharmacological Reviews - April 7, 2020 Category: Drugs & Pharmacology Authors: Savarino V, Marabotto E, Zentilin P, Furnari M, Bodini G, De Maria C, Tolone S, De Bortoli N, Frazzoni M, Savarino E Tags: Expert Rev Clin Pharmacol Source Type: research

A pharmacological profile of intravenous amisulpride for the treatment of post-operative nausea and vomiting.
Abstract INTRODUCTION: The issue of post-operative nausea and vomiting (PONV) remains important in surgical practice, contributing to patient distress, slower recovery and increased use of healthcare resources. Many surgical patients report it to be a worse problem than pain. New antiemetics of different classes are still needed to help manage PONV effectively, especially the treatment of established PONV after the failure of common prophylactic antiemetics such as 5-HT3-antagonists and corticosteroids. Intravenous amisulpride, a drug with a long history of safe use in oral form as an antipsychotic, has recently b...
Source: Pharmacological Reviews - April 3, 2020 Category: Drugs & Pharmacology Authors: Fox G, Kranke P Tags: Expert Rev Clin Pharmacol Source Type: research

More than Smoke and Patches: The Quest for Pharmacotherapies to Treat Tobacco Use Disorder.
Abstract Tobacco use is a persistent public health issue. It kills up to half its users and is the cause of nearly 90% of all lung cancers. The main psychoactive component of tobacco is nicotine, primarily responsible for its abuse-related effects. Accordingly, most pharmacotherapies for smoking cessation target nicotinic acetylcholine receptors (nAChRs), nicotine's major site of action in the brain. The goal of the current review is twofold: first, to provide a brief overview of the most commonly used behavioral procedures for evaluating smoking cessation pharmacotherapies and an introduction to pharmacokinetic a...
Source: Pharmacological Reviews - March 25, 2020 Category: Drugs & Pharmacology Authors: Moerke MJ, McMahon LR, Wilkerson JL Tags: Pharmacol Rev Source Type: research

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution.
Abstract Before it was molecularly cloned in 1994, acute-phase response factor or signal transducer and activator of transcription (STAT)3 was the focus of intense research into understanding the mammalian response to injury, particularly the acute-phase response. Although known to be essential for liver production of acute-phase reactant proteins, many of which augment innate immune responses, molecular cloning of acute-phase response factor or STAT3 and the research this enabled helped establish the central function of Janus kinase (JAK) family members in cytokine signaling and identified a multitude of cytokine...
Source: Pharmacological Reviews - March 22, 2020 Category: Drugs & Pharmacology Authors: Bharadwaj U, Kasembeli MM, Robinson P, Tweardy DJ Tags: Pharmacol Rev Source Type: research

Encoding, Consolidation, and Renormalization in Depression: Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects.
a S Abstract Recent studies have strived to find an association between rapid antidepressant effects and a specific subset of pharmacological targets and molecular pathways. Here, we propose a broader hypothesis of encoding, consolidation, and renormalization in depression (ENCORE-D), which suggests that, fundamentally, rapid and sustained antidepressant effects rely on intrinsic homeostatic mechanisms evoked as a response to the acute pharmacological or physiologic effects triggered by the treatment. We review evidence that supports the notion that various treatments with a rapid onset of action, such as ketamine...
Source: Pharmacological Reviews - March 8, 2020 Category: Drugs & Pharmacology Authors: Rantamäki T, Kohtala S Tags: Pharmacol Rev Source Type: research

Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease.
Abstract The solute carrier family 16 (SLC16) is comprised of 14 members of the monocarboxylate transporter (MCT) family that play an essential role in the transport of important cell nutrients and for cellular metabolism and pH regulation. MCTs 1-4 have been extensively studied and are involved in the proton-dependent transport of L-lactate, pyruvate, short-chain fatty acids, and monocarboxylate drugs in a wide variety of tissues. MCTs 1 and 4 are overexpressed in a number of cancers, and current investigations have focused on transporter inhibition as a novel therapeutic strategy in cancers. MCT1 has also been u...
Source: Pharmacological Reviews - March 8, 2020 Category: Drugs & Pharmacology Authors: Felmlee MA, Jones RS, Rodriguez-Cruz V, Follman KE, Morris ME Tags: Pharmacol Rev Source Type: research

Transitioning from Basic toward Systems Pharmacodynamic Models: Lessons from Corticosteroids.
We describe how many basic PK and PK/PD model components were identified and often applied to the diverse properties of corticosteroids (CS). The CS have complications in disposition and a wide array of simple receptor-to complex gene-mediated actions in multiple organs. Continued assessments of such complexities have offered opportunities to develop models ranging from simple PK to enhanced PK/PD to quantitative systems pharmacology (QSP) that help explain therapeutic and adverse CS effects. Concurrent development of state-of-the-art PK, PK/PD, and QSP models are described alongside experimental studies that revealed dive...
Source: Pharmacological Reviews - March 5, 2020 Category: Drugs & Pharmacology Authors: Ayyar VS, Jusko WJ Tags: Pharmacol Rev Source Type: research

Protein Engineering in the Ubiquitin System: Tools for Discovery and Beyond.
In this study, we highlight recent achievements of protein engineering on mapping, probing, and manipulating UB transfer in the cell. SIGNIFICANCE STATEMENT: The post-translational modification of proteins with ubiquitin alters the fate and function of proteins in diverse ways. Protein engineering is fundamentally transforming research in this area, providing new mechanistic insights and allowing for the exploration of concepts that can potentially be applied to therapeutic intervention. PMID: 32107274 [PubMed - in process] (Source: Pharmacological Reviews)
Source: Pharmacological Reviews - March 1, 2020 Category: Drugs & Pharmacology Authors: Zhao B, Tsai YC, Jin B, Wang B, Wang Y, Zhou H, Carpenter T, Weissman AM, Yin J Tags: Pharmacol Rev Source Type: research

Statins and muscle pain.
Abstract Introduction: Statins remain among the most frequently prescribed drugs and constitute a cornerstone in the prevention of cardiovascular disease. However, muscle symptoms are often reported from patients on statins. Muscle symptoms are frequently reported as adverse events associated with statin therapy.Areas covered: In the present narrative review, statin-associated muscle pain is discussed. It elucidates potential mechanisms and possible targets for management.Expert opinion: In general, the evidence in support of muscle pain caused by statins is in some cases equivocal and not particularly strong. Rep...
Source: Pharmacological Reviews - February 22, 2020 Category: Drugs & Pharmacology Authors: Pergolizzi JV, Coluzzi F, Colucci RD, Olsson H, LeQuang JA, Al-Saadi J, Magnusson P Tags: Expert Rev Clin Pharmacol Source Type: research

Intravenous parecoxib for early postoperative cognitive dysfunction in elderly patients: evidence from a meta-analysis.
CONCLUSION: Perioperative parecoxib administration is effective in reducing the incidence of POCD and improving MMSE score compared with control. However, the beneficial effect of parecoxib has been tested only in Chinese population. Future RCTs in western countries with larger-scale and more comprehensive neurological tests are needed. PMID: 32077347 [PubMed - as supplied by publisher] (Source: Pharmacological Reviews)
Source: Pharmacological Reviews - February 20, 2020 Category: Drugs & Pharmacology Authors: Huang JM, Lv ZT, Zhang B, Jiang WX, Nie MB Tags: Expert Rev Clin Pharmacol Source Type: research

A systems approach to identifying the challenges of implementing deprescribing in older adults across different health care settings and countries: a narrative review.
Abstract Introduction: There is increasing recognition of the need for deprescribing of inappropriate medications in older adults. However, efforts to encourage implementation of deprescribing in clinical practice have resulted in mixed results across settings and countries.Area covered: Searches were conducted in PubMed, Embase and Google Scholar in June 2019. Reference lists, citation checking, and personal reference libraries were also utilised. Studies capturing the main challenges of, and opportunities for, implementing deprescribing into clinical practice across selected health care settings internationally,...
Source: Pharmacological Reviews - February 14, 2020 Category: Drugs & Pharmacology Authors: Sawan M, Reeve E, Turner J, Todd A, Steinman MA, Petrovic M, Gnjidic D Tags: Expert Rev Clin Pharmacol Source Type: research

The European Medicines Agency facilitates access to medicines in low- and middle-income countries.
Discussion: These scientific opinions reflect the conditions of use and rely on high standards, but the final approval decision remains with these countries. Despite the small number of EU-M4all opinions, the many approvals have had an impact and contribute to access to innovation for patients with unmet needs in target countries. PMID: 32053756 [PubMed - as supplied by publisher] (Source: Pharmacological Reviews)
Source: Pharmacological Reviews - February 13, 2020 Category: Drugs & Pharmacology Authors: Cavaller Bellaubi M, Harvey Allchurch M, Lagalice C, Saint-Raymond A Tags: Expert Rev Clin Pharmacol Source Type: research

Inhaled levodopa for intermittent treatment of OFF episodes in patients with Parkinson's disease.
ra JJ Abstract Introduction: Many patients with advanced Parkinson's disease (PD) have inadequate control of motor symptoms despite optimized treatment. Predictable and unpredictable OFF periods severely interfere with quality of life. A drug that easily and rapidly reverts the OFF state is still needed. Subcutaneous apomorphine, the only approved drug for this indication, although efficacious, is not widely used probably due to its potential side effects and complicated administration.Levodopa is the most efficacious drug for the treatment of PD motor symptoms. However, issues related to the oral route and intest...
Source: Pharmacological Reviews - February 3, 2020 Category: Drugs & Pharmacology Authors: Simões RM, Castro Caldas A, Ferreira JJ Tags: Expert Rev Clin Pharmacol Source Type: research

Pharmacodynamics of combined estrogen-progestin oral contraceptives: 4. effects on uterine and cervical epithelia.
Abstract Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequential combined oral contraceptive regimens were utilized. The same basic concept has been utilized with multi-phasic regimens, in order to produce endometrial pictures mimicking the normal cycle.Areas covered: The Endometrial effects of: progestins and estrogens; combined monophasic high- (50μg), medium- (30μg), low- (20μg), ultralow- (15μg) estrogen content; sequential regimens; multiphasic combinati...
Source: Pharmacological Reviews - January 24, 2020 Category: Drugs & Pharmacology Authors: Bastianelli C, Farris M, Bruni V, Brosens I, Benagiano G Tags: Expert Rev Clin Pharmacol Source Type: research

Metabolomics in pharmacology - a delve into the novel field of pharmacometabolomics.
Abstract Introduction: Pharmacometabolomics is an emerging science pursuing the application of precision medicine. Combining both genetic and environmental factors, the so-called pharmacometabolomic approach guides patient selection and stratification in clinical trials and optimizes personalized drug dosage, improving efficacy and safety.Areas covered: This review illustrates the progressive introduction of pharmacometabolomics as an innovative solution for enhancing the discovery of novel drugs and improving research and development (R&D) productivity of the pharmaceutical industry. An extended analysis on p...
Source: Pharmacological Reviews - January 20, 2020 Category: Drugs & Pharmacology Authors: Mussap M, Loddo C, Fanni C, Fanos V Tags: Expert Rev Clin Pharmacol Source Type: research

Aclidinium Bromide and Formoterol Fumarate for the Maintenance Treatment of Chronic Obstructive Pulmonary Disease.
PMID: 31951778 [PubMed - as supplied by publisher] (Source: Pharmacological Reviews)
Source: Pharmacological Reviews - January 17, 2020 Category: Drugs & Pharmacology Authors: Haley R, Gupta N, Sethi S Tags: Expert Rev Clin Pharmacol Source Type: research

Pitolisant for treating patients with narcolepsy.
This article aims to review pitolisant.Areas covered: In this paper the chemical properties, mechanism of action, pharmacokinetics, clinical efficacy and safety of pitolisant was introduced, and the development course of drugs for treating narcolepsy is also briefly described. We performed a systematic review of the literature using PubMed and the following keywords were used: "pitolisant" and "narcolepsy", "cataplexy" and "excessive daytime sleepiness" and "histamine 3 receptor".Expert opinion: Pitolisant is a histamine 3 receptor antagonist/inverse agonist. It can activat...
Source: Pharmacological Reviews - January 15, 2020 Category: Drugs & Pharmacology Authors: Li S, Yang J Tags: Expert Rev Clin Pharmacol Source Type: research

Solute Carrier Transporters as Potential Targets for the Treatment of Metabolic Disease.
AL Abstract The solute carrier (SLC) superfamily comprises more than 400 transport proteins mediating the influx and efflux of substances such as ions, nucleotides, and sugars across biological membranes. Over 80 SLC transporters have been linked to human diseases, including obesity and type 2 diabetes (T2D). This observation highlights the importance of SLCs for human (patho)physiology. Yet, only a small number of SLC proteins are validated drug targets. The most recent drug class approved for the treatment of T2D targets sodium-glucose cotransporter 2, product of the SLC5A2 gene. There is great interest in iden...
Source: Pharmacological Reviews - December 31, 2019 Category: Drugs & Pharmacology Authors: Schumann T, König J, Henke C, Willmes DM, Bornstein SR, Jordan J, Fromm MF, Birkenfeld AL Tags: Pharmacol Rev Source Type: research

Patient and Disease-Specific Induced Pluripotent Stem Cells for Discovery of Personalized Cardiovascular Drugs and Therapeutics.
Abstract Human induced pluripotent stem cells (iPSCs) have emerged as an effective platform for regenerative therapy, disease modeling, and drug discovery. iPSCs allow for the production of limitless supply of patient-specific somatic cells that enable advancement in cardiovascular precision medicine. Over the past decade, researchers have developed protocols to differentiate iPSCs to multiple cardiovascular lineages, as well as to enhance the maturity and functionality of these cells. Despite significant advances, drug therapy and discovery for cardiovascular disease have lagged behind other fields such as oncolo...
Source: Pharmacological Reviews - December 26, 2019 Category: Drugs & Pharmacology Authors: Paik DT, Chandy M, Wu JC Tags: Pharmacol Rev Source Type: research

Organic Cation Transporters in Health and Disease.
Abstract The organic cation transporters (OCTs) OCT1, OCT2, OCT3, novel OCT (OCTN)1, OCTN2, multidrug and toxin exclusion (MATE)1, and MATE kidney-specific 2 are polyspecific transporters exhibiting broadly overlapping substrate selectivities. They transport organic cations, zwitterions, and some uncharged compounds and operate as facilitated diffusion systems and/or antiporters. OCTs are critically involved in intestinal absorption, hepatic uptake, and renal excretion of hydrophilic drugs. They modulate the distribution of endogenous compounds such as thiamine, L-carnitine, and neurotransmitters. Sites of express...
Source: Pharmacological Reviews - December 21, 2019 Category: Drugs & Pharmacology Authors: Koepsell H Tags: Pharmacol Rev Source Type: research

Brothers in Arms: ABCA1- and ABCG1-Mediated Cholesterol Efflux as Promising Targets in Cardiovascular Disease Treatment.
Abstract Atherosclerosis is a leading cause of cardiovascular disease worldwide, and hypercholesterolemia is a major risk factor. Preventive treatments mainly focus on the effective reduction of low-density lipoprotein cholesterol, but their therapeutic value is limited by the inability to completely normalize atherosclerotic risk, probably due to the disease complexity and multifactorial pathogenesis. Consequently, high-density lipoprotein cholesterol gained much interest, as it appeared to be cardioprotective due to its major role in reverse cholesterol transport (RCT). RCT facilitates removal of cholesterol fro...
Source: Pharmacological Reviews - December 15, 2019 Category: Drugs & Pharmacology Authors: Frambach SJCM, de Haas R, Smeitink JAM, Rongen GA, Russel FGM, Schirris TJJ Tags: Pharmacol Rev Source Type: research

The Psychopharmacology of Obsessive-Compulsive Disorder: A Preclinical Roadmap.
Abstract This review evaluates current knowledge about obsessive-compulsive disorder (OCD), with the goal of providing a roadmap for future directions in research on the psychopharmacology of the disorder. It first addresses issues in the description and diagnosis of OCD, including the structure, measurement, and appropriate description of the disorder and issues of differential diagnosis. Current pharmacotherapies for OCD are then reviewed, including monotherapy with serotonin reuptake inhibitors and augmentation with antipsychotic medication and with psychologic treatment. Neuromodulatory therapies for OCD are a...
Source: Pharmacological Reviews - December 14, 2019 Category: Drugs & Pharmacology Authors: Szechtman H, Harvey BH, Woody EZ, Hoffman KL Tags: Pharmacol Rev Source Type: research

Imidazoline Receptor System: The Past, the Present, and the Future.
Li JX Abstract Imidazoline receptors historically referred to a family of nonadrenergic binding sites that recognize compounds with an imidazoline moiety, although this has proven to be an oversimplification. For example, none of the proposed endogenous ligands for imidazoline receptors contain an imidazoline moiety but they are diverse in their chemical structure. Three receptor subtypes (I1, I2, and I3) have been proposed and the understanding of each has seen differing progress over the decades. I1 receptors partially mediate the central hypotensive effects of clonidine-like drugs. Moxonidine and rilmenidine ha...
Source: Pharmacological Reviews - December 12, 2019 Category: Drugs & Pharmacology Authors: Bousquet P, Hudson A, García-Sevilla JA, Li JX Tags: Pharmacol Rev Source Type: research

G Protein-Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action.
Abstract Asthma is a heterogeneous inflammatory disease of the airways that is associated with airway hyperresponsiveness and airflow limitation. Although asthma was once simply categorized as atopic or nonatopic, emerging analyses over the last few decades have revealed a variety of asthma endotypes that are attributed to numerous pathophysiological mechanisms. The classification of asthma by endotype is primarily routed in different profiles of airway inflammation that contribute to bronchoconstriction. Many asthma therapeutics target G protein-coupled receptors (GPCRs), which either enhance bronchodilation or p...
Source: Pharmacological Reviews - November 28, 2019 Category: Drugs & Pharmacology Authors: Wendell SG, Fan H, Zhang C Tags: Pharmacol Rev Source Type: research

Pediatric pharmacokinetics of the antibiotics in the access and watch groups of the 2019 WHO model list of essential medicines for children: a systematic review.
Abstract Introduction: Pharmacokinetic-pharmacodynamic (PK-PD) studies of antibiotics in pediatrics are limited. Pediatric dosing regimens for many antimicrobial drugs have been historically derived from adult pharmacokinetic data. Most pediatric formularies and dosing guidelines globally are expert-based and provide no rationale for the recommended doses, leading to heterogeneous guidance.Areas covered: We systematically reviewed the current dosing for 28 antibiotics listed in the Access and Watch groups of the 2019 World Health Organization (WHO) Essential Medicines List for children (EMLc). PubMed and EMBASE we...
Source: Pharmacological Reviews - November 25, 2019 Category: Drugs & Pharmacology Authors: Rashed AN, Jackson C, Gastine S, Hsia Y, Bielicki J, Standing JF, Tomlin S, Sharland M Tags: Expert Rev Clin Pharmacol Source Type: research

PHARMACOL REV; +165 new citations
165 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: PHARMACOL REV These pubmed results were generated on 2019/11/16PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Pharmacological Reviews)
Source: Pharmacological Reviews - November 16, 2019 Category: Drugs & Pharmacology Tags: Report Source Type: research

PHARMACOL REV; +183 new citations
183 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: PHARMACOL REV These pubmed results were generated on 2019/11/08PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Pharmacological Reviews)
Source: Pharmacological Reviews - November 8, 2019 Category: Drugs & Pharmacology Tags: Report Source Type: research

Sorafenib-associated hand-foot skin reaction: practical advice on diagnosis, mechanism, prevention, and management.
This article reviews known mechanism and management methods of HFSR caused by sorafenib.Areas covered: The author reviews HFSR caused by the treatment of sorafenib including the mechanism and management. English language reports located through PubMed are reviewed.Expert opinion: There are some conjectures about the mechanism of HFSR. However, the mechanism of HFSR induced by sorafenib is still unclear at present. In the absence of understanding the mechanism of HFSR, the most common method for clinical treatment of sorafenib-induced HFSR is dose down-regulation or discontinuation of treatment, which affects efficacy and e...
Source: Pharmacological Reviews - November 2, 2019 Category: Drugs & Pharmacology Authors: Ai L, Xu Z, Yang B, He Q, Luo P Tags: Expert Rev Clin Pharmacol Source Type: research

Novel insights into the pathogenesis of molecular subtypes of diffuse large B-cell lymphoma and their clinical implications.
This article provides an overview of the molecular understanding in DLBCL and highlights potential clinical implications reviewing relevant publications and clinical trials from PubMed and clinicaltrials.gov until August 2019. Expert opinion: Based on gene expression profiling, DLBCL can be divided in two broad subtypes, the activated B-cell-like (ABC) and germinal centre derived (GCB) DLBCL. Recent comprehensive genomic analyses revealed reproducible molecular clusters within the ABC/GCB classification and suggest a more profound molecular characterization to stratify patients within clinical trials. During the last coupl...
Source: Pharmacological Reviews - October 23, 2019 Category: Drugs & Pharmacology Authors: Frontzek F, Lenz G Tags: Expert Rev Clin Pharmacol Source Type: research

Amifampridine tablets for the treatment of Lambert-Eaton myasthenic syndrome.
Abstract Introduction: Lambert-Eaton myasthenic syndrome is an autoimmune disease of the neuromuscular junction characterized by a presynaptic defect of neuromuscular transmission resulting in muscle weakness and fatigability. Diagnostic features are specific neurophysiological alterations and autoantibody detection. The present review is focused on the use of Amifampridine Phosphate to treat LEMS patients. Areas covered: Medline search from 1990 to 2019 was examined using the free subject terms: Lambert-Eaton myasthenic syndrome, LEMS, Amifampridine, 3,4-diaminopyridine, which were then combined with Treatment, T...
Source: Pharmacological Reviews - October 22, 2019 Category: Drugs & Pharmacology Authors: Mantegazza R Tags: Expert Rev Clin Pharmacol Source Type: research

Exploring the neuroregenerative potential of tacrolimus.
Abstract Introduction: The clinical use of tacrolimus is characterized by many side effects which include neurotoxicity. In contrast, tacrolimus has also shown to have neuroregenerative properties. On a molecular level, the mechanisms of action could provide us more insight into understanding the neurobiological effects. The aim of this article is to review current evidence regarding the use of tacrolimus in peripheral nerve injury. Areas covered: Available data on tacrolimus' indications were summarized and molecular mechanisms were elucidated to possibly understand the conflicting neurotoxic and neuroregenerativ...
Source: Pharmacological Reviews - October 1, 2019 Category: Drugs & Pharmacology Authors: Saffari TM, Bedar M, Zuidam JM, Shin AY, Baan CC, Hesselink DA, Hundepool CA Tags: Expert Rev Clin Pharmacol Source Type: research

Plecanatide for the treatment of chronic idiopathic constipation in adult patients.
Abstract Introduction. Chronic idiopathic constipation (CIC) is a functional gastrointestinal disorder that is associated with an increased healthcare cost and an abnormally poor quality of life. Plecanatide is a natural analog to the peptide agonist of the guanylate cyclase-C (GC-C) receptor, uroguanylin. The conversion of guanosine 5-triphosphate to cyclic guanosine monophosphate results in an increased bowel fluid secretion. Plecanatide is a promising new agent for CIC unresponsive to current therapeutic regimes. Areas covered. A comprehensive online search of Medline and the Science Citation Index was made usi...
Source: Pharmacological Reviews - October 1, 2019 Category: Drugs & Pharmacology Authors: Bassotti G, Usai Satta P, Bellini M Tags: Expert Rev Clin Pharmacol Source Type: research

Challenges and Opportunities for Childhood Cancer Drug Development.
Abstract Cancer in children is rare with approximately 15,700 new cases diagnosed in the United States annually. Through use of multimodality therapy (surgery, radiation therapy, and aggressive chemotherapy), 70% of patients will be "cured" of their disease, and 5-year event-free survival exceeds 80%. However, for patients surviving their malignancy, therapy-related long-term adverse effects are severe, with an estimated 50% having chronic life-threatening toxicities related to therapy in their fourth or fifth decade of life. While overall intensive therapy with cytotoxic agents continues to reduce cance...
Source: Pharmacological Reviews - September 29, 2019 Category: Drugs & Pharmacology Authors: Houghton PJ, Kurmasheva RT Tags: Pharmacol Rev Source Type: research

Targeting Foam Cell Formation in Atherosclerosis: Therapeutic Potential of Natural Products.
Abstract Foam cell formation and further accumulation in the subendothelial space of the vascular wall is a hallmark of atherosclerotic lesions. Targeting foam cell formation in the atherosclerotic lesions can be a promising approach to treat and prevent atherosclerosis. The formation of foam cells is determined by the balanced effects of three major interrelated biologic processes, including lipid uptake, cholesterol esterification, and cholesterol efflux. Natural products are a promising source for new lead structures. Multiple natural products and pharmaceutical agents can inhibit foam cell formation and thus e...
Source: Pharmacological Reviews - September 28, 2019 Category: Drugs & Pharmacology Authors: Wang D, Yang Y, Lei Y, Tzvetkov NT, Liu X, Yeung AWK, Xu S, Atanasov AG Tags: Pharmacol Rev Source Type: research

Harnessing Ion-Binding Sites for GPCR Pharmacology.
Abstract Endogenous ions play important roles in the function and pharmacology of G-protein coupled receptors (GPCRs). Historically the evidence for ionic modulation of GPCR function dates to 1973 with studies of opioid receptors, where it was demonstrated that physiologic concentrations of sodium allosterically attenuated agonist binding. This Na+-selective effect was distinct from effects of other monovalent and divalent cations, with the latter usually counteracting sodium's negative allosteric modulation of binding. Since then, numerous studies documenting the effects of mono- and divalent ions on GPCR functio...
Source: Pharmacological Reviews - September 26, 2019 Category: Drugs & Pharmacology Authors: Zarzycka B, Zaidi SA, Roth BL, Katritch V Tags: Pharmacol Rev Source Type: research

Novel Therapeutic Approaches Targeting the Renin-Angiotensin System and Associated Peptides in Hypertension and Heart Failure.
Abstract Despite the success of renin-angiotensin system (RAS) blockade by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor (AT1R) blockers, current therapies for hypertension and related cardiovascular diseases are still inadequate. Identification of additional components of the RAS and associated vasoactive pathways, as well as new structural and functional insights into established targets, have led to novel therapeutic approaches with the potential to provide improved cardiovascular protection and better blood pressure control and/or reduced adverse side effects. The simultaneo...
Source: Pharmacological Reviews - September 22, 2019 Category: Drugs & Pharmacology Authors: Arendse LB, Danser AHJ, Poglitsch M, Touyz RM, Burnett JC, Llorens-Cortes C, Ehlers MR, Sturrock ED Tags: Pharmacol Rev Source Type: research

Druggable Transcriptional Networks in the Human Neurogenic Epigenome.
Abstract Chromosome conformation capture methods have revealed the dynamics of genome architecture which is spatially organized into topologically associated domains, with gene regulation mediated by enhancer-promoter pairs in chromatin space. New evidence shows that endogenous hormones and several xenobiotics act within circumscribed topological domains of the spatial genome, impacting subsets of the chromatin contacts of enhancer-gene promoter pairs in cis and trans Results from the National Institutes of Health-funded PsychENCODE project and the study of chromatin remodeling complexes have converged to provide ...
Source: Pharmacological Reviews - September 19, 2019 Category: Drugs & Pharmacology Authors: Higgins GA, Williams AM, Ade AS, Alam HB, Athey BD Tags: Pharmacol Rev Source Type: research