Current Pharmaceutical Design - Volume 10, Issue 17, 2004

G protein-coupled receptors (GPCRs) comprise the largest class of cell surface receptor proteins and represent the major targets for currently used therapeutic agents. This issue of Current Pharmaceutical Design is the inaugural publication of a series devoted to GPCRs that will broadly deal with the utility of this receptor class in drug development. This issue contains invited review articles from preeminent researchers in the field. Read More

A wide range of peptides and polypeptides can be appended to either the N- or C-terminus of G proteincoupled receptors without disrupting substantially ligand binding and signal transduction. Following fusion of fluorescent proteins, reporter gene constructs or G protein α subunits to the C-terminal tail of a receptor high content and G protein activation assays can be employed to identify agonist ligands. Further modificati Read More

G protein-coupled receptors (GPCRs) constitute the largest receptor superfamily in the human genome and represent the most common targets of drug action. Classic agonist and antagonist ligands that act at GPCRs tend to bind to the receptor's orthosteric site, that is, the site recognized by the endogenous agonist for that receptor. However, it is now evident that GPCRs possess additional, extracellular, allosteric binding sites Read More

Bivalent ligands have been developed for a variety of G protein-coupled receptor targets, including opioid, dopamine, serotonin and muscarinic receptors. The most successful application of the bivalent ligand approach has been in the development of selective opioid antagonists, such as norbinaltorphimine. Several important principles have emerged from the study of norbinaltorphimine and related compounds, including Read More

Adenosine receptors are widely distributed in the body and modulate numerous physiological processes. Four receptor subtypes (termed A1, A2A, A2B and A3) have been identified based on their pharmacological profile and cloning. Activation of the A1 adenosine receptors produces a number of effects including a reduction in heart rate and atrial contractility, the attenuation of the stimulatory actions of catecholamines on the Read More

Combination therapy with reverse transcriptase and protease inhibitors greatly reduces morbidity and mortality in HIV-1-infected individuals. However, current anti-retroviral treatment cannot eradicate the virus from infected individuals and is often limited by the emergence of drug-resistant HIV-1 strains and long-term toxicity. These problems emphasize the need to develop new anti-HIV-1 drugs targeting different st Read More

The aim of antiviral therapy of chronic hepatitis B is to control Hepatitis B Virus (HBV) replication and to cure liver disease avoiding the progression of chronic hepatitis to cirrhosis and the end stage complications of cirrhosis. HBeAg / anti-HBe seroconversion is the hallmark of response in hepatitis B “e” antigen (HBeAg) positive patients. In the patients with antibody against HBeAg (anti-HBe positive) the combination of HBV Read More

Progression from acute to chronic HCV infection occurs in 50% to 84% of cases. In light of the risk of developing chronic disease and the response rate to treatment once the disease is established, it is important to consider early treatment of acute HCV infection before it progresses to the chronic state. Several studies evaluated the efficacy of either alpha or beta IFN monotherapy in patients with acute hepatitis C, but nearl Read More

Ribavirin is a very broad-spectrum anti-viral agent used clinically to treat infections by Lassa fever virus, respiratory syncytial virus (RSV) and, in combination with Interferon-α (IFN-α), hepatitis C virus (HCV). Although it was originally synthesized over 30 years ago, the precise mechanisms of its therapeutic activities are still not fully understood. Ribavirin was shown to possess both direct and indirect action mechanisms against Read More

Previous data demonstrated that an elevated percentage of hepatitis C virus (HCV) infected patients are endotoxemic. Endotoxemic patients are poor responders to the interferon (IFN)- α / ribavirin (RIB) treatment and exhibit lower serum levels of IFN-γ and interleukin (IL)-10 than the responder counterpart. Here we provide evidence that in endotoxemic HCV+ patients absolute numbers of CD19+ cells (B cells) are hig Read More

Combined therapy using Interferon alfa (IFN) and Ribavirin (RIB) represents the standard treatment in patients with chronic hepatitis C. However, the percentage of responders to this regimen is still low, while its cost and side effects are elevated. Therefore, the possibility to predict patient's response to the above treatment is of paramount importance. The progress in the field of informatics and its large use for decision maki Read More

The introduction of highly active anti-retroviral therapy (HAART) for Human Immunodeficiency Virus (HIV) infection has significantly improved the life expectancy of HIV positive patients. Hepatitis C virus (HCV) co-infection is common in HIV infected patients and is now a significant cause of morbidity and mortality. Optimal management and treatment of HCV in HIV infected patients is therefore essential. Interferon-alpha (IF Read More

Hepatitis C virus chronic infection is currently the most common cause of end-stage liver disease. The benefit of antiviral therapy on liver histology and its impact on the long-term course of the disease has been extensively studied. However, the results are still equivocal and the overall assessment of treatment effect remains difficult to evaluate. Although the conclusions of the last National Institute of Health Consensus Read More