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Current Opinion in Pharmacology

Charalambos Vlachopoulos, Christos Georgakopoulos, Iosif Koutagiar, Dimitrios Tousoulis
Peripheral artery disease (PAD) affects approximately one in five persons older than 70 years of age and it is often present in patients with concomitant vascular disease in different body territories (e.g. coronary artery disease). Diagnosis at an early stage is important in order to achieve improvement in patient's symptoms and prognosis. Remarkable improvements in the field of noninvasive and invasive imaging techniques have led to an advanced level the management of patients with PAD. Throughout this review article, the clinically available diagnostic modalities in PAD are presented...
March 14, 2018: Current Opinion in Pharmacology
Richard Teke Ngomba, Gilles van Luijtelaar
Metabotropic glutamate (mGlu) receptors are expressed in key regions of the cortex and the thalamus and are known to regulate spike and wave discharges (SWDs), the electroclinical hallmarks of absence seizures. Recent preclinical studies have highlighted the therapeutic potential of selective group I and III mGlu receptor subtype allosteric modulators, which can suppress pathological SWDs. Of particular interest are positive allosteric modulators (PAMs) for mGlu5 receptors, as they currently show the most promise as novel anti-absence epilepsy drugs...
March 13, 2018: Current Opinion in Pharmacology
Giuseppe Battaglia, Valeria Bruno
Amyotrophic lateral sclerosis (ALS) is a complex genetic, late age-onset, progressive neurodegenerative disorder leading to the death of upper and lower motor neurons. Life expectancy after diagnosis is short due to the ongoing degeneration and to the lack of effective treatments. Axonal alterations, mitochondrial deficits, RNA changes, protein misfolding and turnover, glial dysfunction and hyperexcitability are key players in molecular mechanisms involved in the degeneration of motor neurons. In the context of hyperexcitability, metabotropic glutamate (mGlu) receptors, which are widely distributed throughout the central nervous system and act through many intracellular signaling pathways, are emerging as novel potential drug targets for the therapeutic treatment of ALS, as they are able to counteract excitotoxicity by reducing glutamate release and inducing the production of neurotrophic factors...
March 9, 2018: Current Opinion in Pharmacology
Chakradhari Inampudi, Emmanuel Akintoye, Tomo Ando, Alexandros Briasoulis
Peripheral arterial disease (PAD) refers to narrowing of the peripheral arteries and atherosclerosis is the most important cause. In patients with PAD, revascularization is the preferred therapeutic strategy; nonetheless several patients are not deemed candidates for it due to advanced disease or several comorbidities. The main target of therapeutic angiogenesis is to promote development of new arterial vessels and improve perfusion of ischemic tissue. Angiogenic growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), administered intramuscularly or intra-arterially, have been shown to promote angiogenesis and development of collateral vasculature in preclinical studies...
March 9, 2018: Current Opinion in Pharmacology
Luisa Iacovelli, Rosamaria Orlando, Alessandro Rossi, Paola Spinsanti, Daniela Melchiorri, Ferdinando Nicoletti
In spite of the recent advancement in the molecular characterization of malignant gliomas and medulloblastomas, the treatment of primary brain tumors remains suboptimal. The use of small molecule inhibitors of intracellular signaling pathways, inhibitors of angiogenesis, and immunotherapic agents is limited by systemic adverse effects, limited brain penetration, and, in some cases, lack of efficacy. Thus, adjuvant chemo-therapy and radiotherapy still remain the gold standard in the treatment of grade-IV astrocytoma (glioblastoma multiforme) and medulloblastoma...
March 8, 2018: Current Opinion in Pharmacology
Hirokazu Hirai, Masanobu Kano
Neurodegenerative diseases such as spinocerebellar ataxias and autoantibody-associated disorders of the central nervous system often affect the cerebellum, resulting in motor deficits. Recent studies have revealed that most of these disorders impair type 1 metabotropic glutamate receptor (mGluR1) and/or the closely associated signaling molecules in cerebellar Purkinje cell. Since the signaling pathway triggered by mGluR1 activation in Purkinje cell plays a pivotal role in coordinated movements and motor learning, pharmacological repair of aberrant mGluR1 signaling in Purkinje cell is critical for mitigation of cerebellar symptoms...
March 8, 2018: Current Opinion in Pharmacology
Andrea Bianco, Umberto Malapelle, Danilo Rocco, Fabio Perrotta, Gennaro Mazzarella
Cancers have the ability to disrupt immune response by interfering with adaptive immunity. Blocking checkpoint pathways has become a target for pharmacological research in lung cancer with particular focus on peptides PD-1 and CTLA-4. A number of immune check-point inhibitors (ICIs) targeting both PD-1 and CTLA-4 pathways are under investigation within clinical trials, of which Nivolumab, Pembrolizumab and Atezolizumab have already been approved for lung cancer treatment by both FDA and EMA. Employed as single-agents in current practice for the treatment of advanced non-small cell lung cancer (NSCLC) ICIs have exhibited advantages in terms of overall survival and response rate with some responses being durable...
March 8, 2018: Current Opinion in Pharmacology
Francesco Ferraguti
Anxiety disorders are highly prevalent psychiatric illnesses posing an important social and economic burden. Their current pharmacotherapy shows short term efficacy, though nearly one third of patients do not achieve sustained remission. There is, therefore, a strong medical need for new therapeutic agents acting through novel mechanisms of action. Considerable work has focused on metabotropic glutamate (mGlu) receptors as potential targets for novel anxiolytics. Ligands acting at mGlu receptors showed promising results in preclinical studies, whereas their efficacy was dubious in clinical trials...
February 26, 2018: Current Opinion in Pharmacology
Georgios Giannopoulos, Christos Angelidis, Georgia Vogiatzi, Michael W Cleman, Spyridon Deftereos
Peripheral arterial disease is a major cause of morbidity and disability and has been consistently associated with an adverse overall prognosis. Oxidative stress has been linked to vascular disease, with several suggested pathogenetic mechanisms, leading to various insults of the arterial wall and, ultimately, to atherothrombotic disease. Considering that the pathophysiological background is quite compelling, attenuation of oxidative processes by means of various substances with antioxidant properties has been conceived as a promising therapeutic target...
February 24, 2018: Current Opinion in Pharmacology
Branden J Stansley, P Jeffrey Conn
Accumulating evidence suggests that a dysregulation of the glutamatergic system exists in the brains of schizophrenia patients. The metabotropic glutamate (mGlu) receptors are being investigated as novel drug targets for this disease, and have shown promise in both preclinical and clinical studies. Activation of mGlu5 receptors may be efficacious for several symptom domains (positive, negative, and cognitive) and the potential for targeting mGlu5 receptors has been bolstered by recent research on mitigating toxicity profiles associated with mGlu5 activation...
February 24, 2018: Current Opinion in Pharmacology
Shigeyuki Chaki, Kenichi Fukumoto
Ever since the discovery of the rapid and sustained antidepressant effect of ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist, agents acting on the glutamatergic system have been explored for their potential as novel antidepressants. Among the glutamategic system, metabotropic glutamate (mGlu) receptors, which play important roles in regulating glutamate transmission, have recently gained much attention as potential targets for the development of novel antidepressants. Of these, the antidepressant effects of agents acting on the mGlu2/3 receptor and mGlu5 receptor have been well characterized in several animal models...
February 24, 2018: Current Opinion in Pharmacology
Francesco Fazio, Martina Ulivieri, Claudia Volpi, Marco Gargaro, Francesca Fallarino
A large body of evidence suggests that neuroinflammation lies at the core of nearly all CNS disorders, including psychiatric disorders. Invading and local immune cells orchestrate the series of events that lead to either tissue repair or damage in response to neuroinflammation. Both lymphocytes and microglia express metabotropic glutamate (mGlu) receptors, which respond to glutamate or other endogenous activators (e.g. some kynurenine metabolites of tryptophan metabolism) influencing immune phenotype and the balance between pro-inflammatory and anti-inflammatory cytokines...
February 19, 2018: Current Opinion in Pharmacology
Vasiliki Tsigkou, Gerasimos Siasos, Kleanthis Rovos, Niki Tripyla, Dimitris Tousoulis
Peripheral artery disease (PAD) is one of the most important causes of cardiovascular morbidity and mortality and its prevalence is alarmingly increasing in modern societies. PAD shares common characteristics with the other atherosclerotic diseases but involves specifically the arteries of the lower extremities. Apart from the changes in lifestyle, antiplatelet agents are the hallmark of the treatment and improve the symptoms as well as the progression of the disease. Aspirin is the cornerstone of treatment and is administrated in doses ranging from 75 to 325mg daily...
February 19, 2018: Current Opinion in Pharmacology
Costas Tsioufis, Ioannis Andrikou, Gerasimos Siasos, Konstantinos Filis, Dimitrios Tousoulis
Peripheral artery disease (PAD) affects more than 200 million people worldwide. Hypertension has been related to increased risk of PAD. The treatment of elevated blood pressure (BP) in these patients is indicated to lower the cardiovascular risk with a BP goal of less than 130/80mmHg. Although there is no evidence that one class of antihypertensive medication or strategy is superior for BP lowering in PAD, the use of renin-angiotensin-system (RAS) inhibitors can be effective to reduce the cardiovascular risk...
February 16, 2018: Current Opinion in Pharmacology
Janis K Shute, Ermanno Puxeddu, Luigino Calzetta
In this review, we identify potential targets for the therapeutic effects of heparin in asthma and chronic obstructive pulmonary disease (COPD), consider the safety and delivery modalities of this therapeutic approach. Specifically, we point to the anti-inflammatory, antioxidant and mucolytic effects of unfractionated heparin with potential to modify disease progression in COPD and asthma when administered via the inhaled route. Inhaled heparin may represent an effective add-on therapy in COPD and asthma patient groups, especially when taking into consideration the relative deficiency in endogenous heparin reported in asthma patients...
February 15, 2018: Current Opinion in Pharmacology
Cyril Goudet, Xavier Rovira, Amadeu Llebaria
Metabotropic glutamate receptors (mGluRs) are a family of G protein-coupled receptors activated by glutamate, the main excitatory neurotransmitter of the mammalian central nervous system. These receptors are considered as potential therapeutic targets in many neurological diseases but a better understanding of their complex molecular dynamics and of their role in the normal and pathological functioning of the brain is still required. Manipulating mGluRs with high spatial and temporal precision holds great promise for deciphering their physiological and pathological functions...
February 15, 2018: Current Opinion in Pharmacology
Nikolaos G Frangogiannis
Patients with severe peripheral artery disease (PAD) who are not candidates for revascularization have poor prognosis. Cell therapy using peripheral blood-derived or bone marrow-derived mononuclear cells, mesenchymal stem cells, or marker-specific subsets of bone marrow cells with angiogenic properties may hold promise for no-option PAD patients. Injected cells may exert beneficial actions by enhancing local angiogenesis (either through maturation of endothelial progenitors, or through secretion of angiogenic mediators), or by transducing cytoprotective signals that preserve tissue structure...
February 13, 2018: Current Opinion in Pharmacology
Paola Rogliani, Josuel Ora, Nicola Di Daniele, Davide Lauro
Diabetes mellitus (DM) is a complex multifactorial disease due to the interaction between environmental noxae and genetic predisposition. Furthermore, an increased association between DM, especially Type 2 diabetes mellitus (T2DM), and the onset of pulmonary function impairment with a bronchial hyperresponsiveness has been documented. DM is a risk factor for accelerated decline in FEV1 and the development of asthma and COPD. The increased blood glucose concentrations along with higher levels of oxidative stress and inflammation can influence the pulmonary function and, since hypoglycemic drugs can act on these different defects we can hypothesize their direct effect on obstructive pulmonary diseases...
February 7, 2018: Current Opinion in Pharmacology
Purna C Kayshap, Eamonn Mm Quigley
Gut microbiome is an integral part of the metabolic machinery that contributes to normal host function. The advent of next generation sequencing technologies has allowed an in-depth investigation of the microbiome at various body sites including microbes which are challenging to culture. The same technologies have revealed the metabolic capacity of the microbiome, identified novel microbial products and suggested possible implications for human health. The gut microbiome has previously not been considered in aspects of human health such as response to medications, which may be metabolized to a varying extent by the microbiome, thereby, altering their efficacy and the incidence of adverse events...
February 6, 2018: Current Opinion in Pharmacology
Niki Katsiki, Athanasios D Giannoukas, Vasilios G Athyros, Dimitri P Mikhailidis
Peripheral artery disease (PAD) is characterized by increased cardiovascular (CV) risk, limb morbidity and all-cause mortality. According to the current guidelines (2016) of the American Heart Association/American College of Cardiology on the management of PAD patients, statin therapy is recommended for PAD patients in order to treat dyslipidemia and reduce CV risk. The present narrative review discusses the use of statins and other lipid-lowering drugs such as ezetimibe, fibrates, niacin, anacetrapib and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in PAD patients in terms of both CV and limb outcomes...
January 31, 2018: Current Opinion in Pharmacology
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