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Third Generation Antipsychotic Drugs: Partial Agonism or Receptor Functional Selectivity?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Functional selectivity is the term that describes drugs that cause markedly different signaling through a single receptor (e.g., full agonist at one pathway and antagonist at a second). It has been widely recognized recently that this phenomenon impacts the understanding of mechanism of action of some drugs, and has relevance to drug discovery. One of the clinical areas where this mechanism has particular importance is in the treatment of schizophrenia. Antipsychotic drugs have been grouped according to both pattern of clinical action and mechanism of action. The original antipsychotic drugs such as chlorpromazine and ...
Source: Current Pharmaceutical Design - November 12, 2009 Category: Drugs & Pharmacology Authors: Mailman RB, Murthy V Tags: Curr Pharm Des Source Type: journals

Unraveling Monoamine Receptors Involved in the Action of Typical and Atypical Antipsychotics on Glutamatergic and Serotonergic Transmission in Prefrontal Cortex.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The systemic administration of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists has been considered as a pharmacological model of schizophrenia. In the present work, we used in vivo microdialysis to examine: first, the effects of MK-801, on the efflux of glutamate and serotonin (5-HT) in the medial prefrontal cortex (mPFC) of the rat; second, whether the MK-801-induced changes in the cortical efflux of both transmitters could be blocked by atypical (clozapine and olanzapine) and classical (haloperidol and chlorpromazine) antipsychotic drugs given intra-mPFC; and third, the role of local blockade of dopam...
Source: Current Pharmaceutical Design - November 12, 2009 Category: Drugs & Pharmacology Authors: López-Gil X, Artigas F, Adell A Tags: Curr Pharm Des Source Type: journals

Strategies to Enhance N-Methyl-D-aspartate Receptor-Mediated Neurotransmission in Schizophrenia, a Critical Review and Meta-Analysis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although hypofunction of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission is proposed to play an important role in the pathophysiology of schizophrenia, results of the clinical trials of small molecules that enhance the NMDA function are inconsistent. A meta-analysis of all the double-blind, placebo-controlled studies in patients with schizophrenia was performed to examine their efficacy on different symptom domains, the dose-response, the effects of concomitant antipsychotics, and their side effects. About eight hundred subjects from 26 studies were included in current meta-analysis. Overall, the NMDA-e...
Source: Current Pharmaceutical Design - November 12, 2009 Category: Drugs & Pharmacology Authors: Tsai GE, Lin PY Tags: Curr Pharm Des Source Type: journals

Antipsychotic Medication: The Potential Role of 5-HT(1A) Receptor Agonism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Schizophrenia is a complex psychiatric disorder characterised by positive and negative symptoms, cognitive impairments, attentional problems, anxiety and depressive symptoms. The use of atypical antipsychotics has generally improved clinical outcome yet medical need remains in the treatment of this disease. The potential use of 5-HT(1A) receptor agonism is emerging as one potential area that could be exploited to improve clinical management of the disease. 5-HT(1A) receptor agonism will not reduce hyperprolactinaemia but does appear to enhance effects on positive, negative and cognitive symptoms and also treat attentio...
Source: Current Pharmaceutical Design - November 12, 2009 Category: Drugs & Pharmacology Authors: McCreary AC, Jones CA Tags: Curr Pharm Des Source Type: journals

Targeting alpha7 Nicotinic Acetylcholine Receptors in the Treatment of Schizophrenia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The most abundant homomeric nicotinic acetylcholine receptors (nAChRs) in the mammalian brain are the pentameric alpha7 nAChRs which consist of five alpha7 subunits, and each subunit provides an orthosteric low affinity binding site for its endogenous ligand, acetylcholine. Distribution and high level expression of alpha7 nAChRs within the limbic circuitry, including the hippocampus and prefrontal cortical areas are in line with their involvement in various cognitive functions. Activation of alpha7 nAChRs generates a conformational change of sub-unit proteins, making the channel permeable to cations, in particular calc...
Source: Current Pharmaceutical Design - November 12, 2009 Category: Drugs & Pharmacology Authors: Hajós M, Rogers BN Tags: Curr Pharm Des Source Type: journals

Anti-Infective Strategies of the Future: Is there Room for Species-Specific Antibacterial Agents?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Broad-spectrum antibiotics, directed against conserved bacterial targets, are the mainstay of antibacterial therapy. Increasing resistance, however, demands new strategies. Over time a number of therapeutic concepts have evolved, starting out with the use of polyclonal antisera, which were rapidly replaced by the easier to use antibiotics. Other concepts, such as immunotherapy, radioimmunotherapy, anti-virulence agents, phage therapy and others are under evaluation and often limited in application. In the discovery process of new antibiotics in the pharmaceutical industry quite a number of new agents have emerged, whic...
Source: Current Pharmaceutical Design - November 10, 2009 Category: Drugs & Pharmacology Authors: Then RL, Sahl HG Tags: Curr Pharm Des Source Type: journals

Can Microbicides Turn the Tide against HIV?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The global impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is increasing and traditional preventative 'safe sex' strategies do not seem to be slowing the spread of this virus. With an efficacious vaccine at least a decade away, the only strategy to avoid the ever-increasing cost of highly active antiretroviral therapy (HAART) is to develop new methods that prevent virus transmission. Microbicides are topically-applied molecules that disrupt the HIV cycle and block infection. This review discusses the current state of the art in microbicide development, looking at the most clinically...
Source: Current Pharmaceutical Design - November 10, 2009 Category: Drugs & Pharmacology Authors: Ramessar K, Sabalza M, Miralpeix B, Capell T, Christou P Tags: Curr Pharm Des Source Type: journals

MHC and MHC-Like Molecules in the Design of Vaccines.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19860670 [PubMed - in process] (Source: Current Pharmaceutical Design)
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Apostolopoulos V Tags: Curr Pharm Des Source Type: journals

Prediction of MHC-Peptide Binding: A Systematic and Comprehensive Overview.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report, we will systematically examine the available methods for predicting MHC-peptide binding and discuss their most relevant advantages and drawbacks. PMID: 19860671 [PubMed - in process] (Source: Current Pharmaceutical Design)
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Lafuente EM, Reche PA Tags: Curr Pharm Des Source Type: journals

Characterization of MHC ligands for Peptide based tumor vaccination.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe the details of the HLA-B*3801 peptide motif by comparing features of natural MHC ligands, resulting in a scoring matrix that enables epitope prediction from any viral or tumor antigen. The pronounced individuality in peptide presentation by MHC molecules, as reflected in the highly specific peptide motifs of different MHC allotypes or the tissue-specific MHC ligandomes, represents a current area of interest within this field. Finally, the identification of post-translational modifications - most important phosphorylations - and the promises this holds will be discussed in this chapter. PMID: 19860672 [PubMe...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Klug F, Miller M, Schmidt HH, Stevanović S Tags: Curr Pharm Des Source Type: journals

Models of antigen receptor activation in the design of vaccines.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Vaccination techniques have developed rapidly over the last several decades from the immunization with live attenuated pathogens to the use of peptide and DNA subunit vaccines, from the use of classical adjuvants to cell-directed delivery. Vaccination techiques are also under investigation for the treatment of tumors and autoimmune diseases. However, profound knowledge of activation mechanisms of the immune cells on a molecular level is prerequisite for a better understanding of the immune response, and for the development of effective immunomodulatory tools. In this review we discuss the models of BCR and TCR activati...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Molnár E, Dopfer EP, Deswal S, Schamel WW Tags: Curr Pharm Des Source Type: journals

HLA-DR: Molecular Insights and Vaccine Design.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Vaccines are one of the most cost effective methods to control infectious diseases and at the same time one of the most complex products of the pharmaceutical industry. In contrast to other drugs, vaccines are used mainly in healthy individuals, often in children. For this reason, very high standards are set for their production. Subunit vaccines, especially peptide vaccines, can provide a safe and cost-effective alternative to vaccines produced from attenuated or inactivated pathogen preparations. Biochemical and structural studies of class II MHC - peptide complexes are beginning to provide a conceptual foundation fo...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Stern LJ, Calvo-Calle JM Tags: Curr Pharm Des Source Type: journals

Use of MHC II Structural Features in the Design of Vaccines for Organ-Specific Autoimmune Diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Major Histocompatibility Complex Class II locus is the primary genetic linkage to autoimmune diseases. Susceptibility to each such disease is linked to different alleles, with a few alleles showing also dominant protection. The design of vaccines for autoimmune diseases is a long sought-after goal. As knowledge about the pathogenesis of these diseases has increased, the tools for such an approach have of necessity been refined. We review below the structural essence of MHC II-linked autoimmune diseases which centers on the binding of antigenic peptides to the disease-linked MHC II proteins, and the consequent activ...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Moustakas AK, Papadopoulos GK Tags: Curr Pharm Des Source Type: journals

Non-canonical peptides bound to MHC.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Central to the initiation of a T cell dependent immune response is the recognition of major histocompatibility complex (MHC) class I or class II molecules (in humans termed HLA and in mice termed H-2) bound to antigenic peptide. T cell receptors (TCR) have programmed specificity for particular peptide/MHC complexes, which ensures focused immune responses are generated against the antigen source. To design effective peptide based vaccines a comprehensive understanding of the specific interactions between MHC molecules and peptide, and of TCR recognition of MHC/peptide is valuable. We place particular emphasis on non-can...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Day SL, Ramsland PA, Apostolopoulos V Tags: Curr Pharm Des Source Type: journals

"Self-nonself" peptides in the design of vaccines.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
What makes a peptide an epitope? This is a central question in immunology. The clear identification of precise molecular characteristics of epitopes would help define the basic mechanisms of self/non-self distinction and lead to a greater understanding of phenomena such as tolerance, autoimmunity, allergy, and tumor escape of immune surveillance. Importantly, clarifying the properties an epitope is paramount to the development of diagnostic and therapeutic vaccines. This review analyzes recent reports on experimentally identified B cell epitopes associated with multiple infectious disease pathologies, cancer, autoimmun...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Kanduc D Tags: Curr Pharm Des Source Type: journals

The TCR/CD3 Complex: Opening the Gate to Successful Vaccination.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The success of vaccination is directly or indirectly based on the specificity of antigen recognition by T lymphocytes, their efficient activation and expansion, and the generation of vaccine-specific effectors and memory cells. These traits are largely dependent on the correct assembly and expression of sufficient number of functional TCR/CD3 complexes in the cell surface. In this review, some of the genetic and epigenetic factors that determine the correct assembly and structure of the TCR/CD3 complex are summarized. Those physiologic or pathologic factors leading to natural variations, or pathologic alterations of th...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Portolés P, Rojo JM Tags: Curr Pharm Des Source Type: journals

NK cell receptors and their interactions with MHC.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
MHC-specific Natural Killer inhibitory receptors display a conserved and fundamental function in the regulation of NK-mediated cytolysis. Their importance is substantiated by the fact that during speciation different molecular receptor structures have evolved to maintain inhibitory regulation of NK cells. The information gained during these last twenty years begins to be fruitfully used in the therapy of leukemias, but a lot has to be still done. In particular, we need to understand the role of activating KIR and their ligand(s), since their role in the course of different viral diseases is still intriguing. PMID: ...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Biassoni R, Ugolotti E, De Maria A Tags: Curr Pharm Des Source Type: journals

Presentation of Lipid Antigens by CD1 Glycoproteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CD1 molecules are a family of non-polymorphic, class I antigen-presenting glycoproteins, which bind and present amphiphilic lipid antigens for recognition to T cells. Two groups of CD1 molecules are involved in presentation of self and foreign lipid antigens: group 1 (CD1a, CD1b and CD1c) and group 2 (CD1d). Crystal structures of CD1a, CD1b and CD1d in complex with different ligands have revealed the key principles of lipid presentation and defined unique binding groove architectures for the individual CD1 isoforms, which enable binding and presentation of an enormous variety of lipids. Structural and biochemical insig...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Schiefner A, Wilson IA Tags: Curr Pharm Des Source Type: journals

HLA-G Molecule.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human leukocyte antigen-G (HLA-G) is a non-classical HLA class I molecule, which was first discovered in 1987 by Geraghty and colleagues [1]. While classical HLA class I molecules are expressed on all nucleated cells, the expression of the HLA-G molecule is highly tissue-restricted, such as to placental trophoblast cells. HLA-G binds inhibitory receptors such as leukocyte immunoglobulin-like receptors B1 (LILRB1/ILT2/CD85j) and LILRB2 (ILT4/CD85d), which are widely expressed on immune cells, to suppress a broad range of immune responses [2-4]. Thus, the expression of HLA-G in placenta protects the fetus from the matern...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Kamishikiryo J, Maenaka K Tags: Curr Pharm Des Source Type: journals

HPLC and MS Analysis for the Identification and Characterisation of Peptides Presented in the Context of the Non-Classical Human Leukocytes Antigen (HLA) Class I Molecule HLA-E.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In addition to a variety of other techniques used in T-cell epitope identification, mass spectrometery coupled to liquid chromatography have now become an important and sensitive tool in separation, detection, and sequence analysis of highly complex natural major histocompatibility complex (MHC) ligand mixtures. In this article, we present current strategies for the identification of MHC eluted peptides using high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) with a particular recall to those presented in the context of the non classical human leukocytes antigen (HLA) class I molecu...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Millo E, Damonte G Tags: Curr Pharm Des Source Type: journals

HLA-E and HLA-E-Bound Peptides: Recognition by Subsets of NK and T Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In humans, major histocompatibility complex (MHC) class I molecules comprise the classical (class Ia) human leukocyte antigens (HLA)-A, -B, and -C, and the non-classical (class Ib) HLA-E, -F, -G and -H (HFE) molecules. The best-characterized MHC class Ib molecule is HLA-E. HLA-E was first described as a non-polymorphic ligand of the CD94/NKG2 receptors expressed mainly by natural killer (NK) cells and its role was thus confined to the regulation of NK cell function. Therefore, interaction of HLA-E with the CD94/NKG2 receptors can result in either inhibition or activation of NK cells, depending on the peptide presented ...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Pietra G, Romagnani C, Moretta L, Mingari MC Tags: Curr Pharm Des Source Type: journals

Simultaneous Optimization of Potency, Selectivity and Physicochemical Properties for Cannabinoid CB(2) Ligands.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Non-selective cannabinoid ligands display a wide range of physiological effects including analgesic, anti-inflammatory, anti-convulsive and immuno-suppressive activities. A separation between therapeutic effects and undesirable CNS side effects may be accomplished by increasing the selectivity for the CB(2) receptor over the CB(1) receptor. There is considerable interest in developing new cannabimimetic compounds possessing preferentially high affinity for the CB(2) receptor as potential novel therapeutics for the treatment of inflammation and chronic pain. This review will summarize the literature on selective cannabi...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Worm K, Dolle RE Tags: Curr Pharm Des Source Type: journals

Pathophysiological insights into atrial fibrillation following cardiac surgery: implications for current pharmaceutical design.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Atrial fibrillation (AF) following cardiac surgery is a common complication, which increases incidence of other complications, hospital and healthcare costs. The reported rate of the occurrence of postoperative AF varies with different studies, depending on population profile, type of surgery, arrhythmia definition and detection methods, design of study. Nonetheless, the precise mechanisms of AF related to cardiac surgery are poorly understood. A diverse variety of reasons have been proposed for the pathogenesis of this common cardiac arrhythmia. The aim of this review article is to provide an overview of pathophysiolo...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Kaireviciute D, Aidietis A, Lip GY Tags: Curr Pharm Des Source Type: journals

Developing novel therapeutic approaches to frailty.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article reviews the drugs available and those under development. While, at present, exercise is the primary therapy, it is expected over the next decade that numerous drugs will be available to treat components of the frailty syndrome. PMID: 19860686 [PubMed - in process] (Source: Current Pharmaceutical Design)
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Morley JE Tags: Curr Pharm Des Source Type: journals

Role of chemokines and their receptors in cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Metastases are the cause of 90% of human cancer deaths. The current treatment of cancer with chemo,- and/or radiotherapy is based on cell death by DNA damage neglecting the fact that cancer cell invasion into surrounding tissues and metastasizing are fundamental features of neoplasms and the major reason for treatment failure. Metastasis is the result of several sequential steps and represents a highly organized, non-random, and organ-selective process. A number of in vitro and in vivo models show that tumor cells use chemokine-mediated mechanisms during this metastasizing process, comparable to those observed in the r...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Kruizinga RC, Bestebroer J, Berghuis P, de Haas CJ, Links TP, de Vries EG, Walenkamp AM Tags: Curr Pharm Des Source Type: journals

Vascular damage in impaired glucose tolerance: an unappreciated phenomenon?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Impaired glucose tolerance (IGT) is an independent risk predictor for cardiovascular morbidity and mortality, as well as for total mortality, independent of the subsequent development of overt diabetes mellitus. Increased rates of major adverse cardiac event and shorter survival in subjects with IGT who are post acute myocardial infarction have also been observed. The aim of this review article is to provide an overview of the pathophysiological basis of IGT and the actual mechanism(s) of vascular damage, accounting for its impact in cardiovascular disease (CVD). We focus on endothelial damage, aberrant angiogenesis an...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Jessani S, Millane T, Lip GY Tags: Curr Pharm Des Source Type: journals

Mast cells: target and source of neuropeptides.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mast cells, originating from bone marrow pluripotential cells are generally populated near to strategic locations of mammalian body. They store a wide variety of biologically active molecules in their granules and also can de novo synthesize an additional spectrum of mediators, depending on their microenvironment, phenotype and status. Mast cells have numerous receptors that can trigger a wide spectrum of cellular responses, some of them which can be preprogrammed against specific pathogens. Mast cells secrete mediators, go under total degranulation, or degranulate only some of the specific granules with required conte...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Tore F, Tuncel N Tags: Curr Pharm Des Source Type: journals

Drug combinations for dyslipidemia and obesity treatment in metabolic syndrome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Metabolic syndrome (MetS) is a cluster of risk factors, each one individually associated with increased cardiovascular disease risk. Treatment of all components of MetS is expected to result in reduced risk. Treatment of MetS mainly includes lifestyle changes. In addition, drug therapy may be considered, especially combinations of different drugs, in order to tackle all the features of MetS. We review the therapeutic strategies currently used for obesity and dyslipidemia treatment in patients with MetS, with a focus on drug combinations. PMID: 19860690 [PubMed - in process] (Source: Current Pharmaceutical Design)
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Florentin M, Elisaf MS, Mikhailidis DP, Liberopoulos EN Tags: Curr Pharm Des Source Type: journals

Phosphodiesterase-5 Inhibitors and their Use in the Treatment of Urological Conditions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19860691 [PubMed - in process] (Source: Current Pharmaceutical Design)
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Petros P Tags: Curr Pharm Des Source Type: journals

PDE5 Inhibitors: In Vitro and In Vivo Pharmacological Profile.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PDE5 inhibitors have been clearly established as first-line therapy for the treatment of erectile dysfunction (ED). Three PDE5 inhibitors - sildenafil (Viagra((R))), vardenafil (Levitra((R))) and tadalafil (Cialis((R))) - are currently approved by the FDA and the EMEA for use in ED, whereas sildenafil is also marketed under a different proprietary name (Revatio((R))) for the treatment of pulmonary arterial hypertension (PAH). A forth PDE5 inhibitor, udenafil (Zydena((R))), is currently marketed. In the present review the molecular basis and the mechanism of action of PDE5 inhibitors is discussed. In addition experiment...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Kouvelas D, Goulas A, Papazisis G, Sardeli C, Pourzitaki C Tags: Curr Pharm Des Source Type: journals

Phosphodiesterase type 5 inhibitors: unmet needs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Erectile dysfunction (ED) has been revolutionized during the last two decades, as several treatment options are available today. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, vardenafil) are currently the first choice treatment option for ED by most physicians and patients due to their high efficacy rates and favourable safety profiles. Despite the fact that more than 50 million ED patients have been treated successfully worldwide with PDE5i several issues remain to be addressed. Patients with severe neurologic damage, diabetes mellitus, or severe vascular disease may be resistant to PDE5i. Inappro...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Hatzimouratidis K, Hatzichristou DG Tags: Curr Pharm Des Source Type: journals

Phosphodiesterase type 5 inhibitors for the management of erectile dysfunction: preference and adherence to treatment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article examines the peer-reviewed published data addressing patient's preference and adherence to ED treatment with PDE5 inhibitors. It also examines strategies to improve compliance and satisfaction with treatment. PMID: 19860694 [PubMed - in process] (Source: Current Pharmaceutical Design)
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Al-Shaiji TF, Brock GB Tags: Curr Pharm Des Source Type: journals

Prophylaxis of erectile function after radical prostatectomy with phosphodiesterase type 5 inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Erectile dysfunction (ED) is one of the most challenging complications associated with radical prostatectomy (RP) for clinically localized prostate cancer. Currently, a broad spectrum of therapeutic options are available to improve sexual health after surgical treatment. Several basic science reports highlighted a potential role for phosphodiesterase type 5 inhibitors in the prevention of endothelial damage related to ischemia reperfusion and/or denervation following surgery. Recent studies have shown that pharmacological prophylaxis soon after RP can significantly improve the rate at which erectile function is recover...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Deho F, Gallina A, Salonia A, Briganti A, Suardi N, Zanni G, Guazzoni G, Rigatti P, Montorsi F Tags: Curr Pharm Des Source Type: journals

PDE5 Inhibitors in the Treatment of LUTS.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) have a negative impact on patients' quality of life. The co-prescription of two active agents for these conditions will improve each condition and the addition of one drug to the other may potentiate the primary response of the first treatment and thereby improve the QoL of patients. Several epidemiological studies have indicated that the association between LUTS and ED is more than a co-incidence of age, with a possible cause and effect relationship. LUTS is more common in men with ED and there is a strong relationship between the severity of LUTS ...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Speakman MJ Tags: Curr Pharm Des Source Type: journals

Is There a Role for PDE5 Inhibitors in the Management of Male Infertility Due to Defects in Testicular or Epididymal Function?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This review study refers to the possibility to employ PDE5 inhibitors as an adjunct tool for the therapeutic management of male infertility. The literature tends to suggest that PDE5 inhibitors enhance the Leydig cell secretory function and play a role in the regulation of the contractility of the tunica albuginea and the epididymis. In addition, the literature suggests that PDE5 inhibitors increase the prostatic secretory function that results in an improvement in sperm motility in several cases. Some studies additionally demonstrate a role of PDE5 inhibitors in the regulation of sperm capacitation process. Additional...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Dimitriadis F, Tsounapi P, Saito M, Watanabe T, Sylakos A, Tsabalas S, Miyagawa I, Sofikitis N Tags: Curr Pharm Des Source Type: journals

PDE5 Inhibitors in Non-Urological Conditions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Phosphodiesterase type-5 (PDE5) inhibitors are widely used as first-line therapy for erectile dysfunction (ED). Their efficacy and safety combined with an increasing understanding of cyclic guanosine monophosphate (cGMP)-regulated mechanisms, have triggered a number of attempts to determine their effects and potential benefits in non-urological conditions. In recent years, extensive and diverse preclinical and clinical evidence has been made available. PDE5 inhibition has shown collateral benefits for a multitude of risk factors or diseases associated with, or accompanying ED. To date, PDE5 inhibition has been shown to...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Vlachopoulos C, Terentes-Printzios D, Ioakeimidis N, Rokkas K, Stefanadis C Tags: Curr Pharm Des Source Type: journals

Phosphodiesterase-5 inhibitors: future perspectives.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PDE-5 inhibitors were originally studied in cardiovascular indications but were later developed and approved for on-demand treatment of erectile dysfunction (ED). A few years ago sildenafil was approved for the treatment of pulmonary hypertension, thus renewing interest in cardiovascular applications, and tadalafil became available in once-daily formulations for erectile dysfunction management. Given the wide distribution of phosphodiesterase-5 throughout the body and its involvement in multiple functions, what can one expect in the future? To answer this we reviewed studies involving PDE-5 inhibitors that were publish...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Konstantinos G, Petros P Tags: Curr Pharm Des Source Type: journals

Recent advances of fluorescent technologies for drug discovery and development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent progresses in the development of fluorescent technologies become a reliable device for drug discovery research. The fluorescence tools offer attractive options for an opportunity to visualize the effects of drug candidates in the cells. The fluorescent tools, such as fluorescent protein, are regularly used in a range of drug discovery processes. A better understanding and use of fluorescent technologies facilitate drug discovery research faster and can open up new applications. Therefore, we have provided information about some new generation fluorescent reagents (GFP and fluorophores). This review illustrates h...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Chakraborty C, Hsu CH, Wen ZH, Lin CS Tags: Curr Pharm Des Source Type: journals

Role of calcitonin gene-related Peptide in gastric mucosal defence and healing.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Calcitonin gene-related peptide (CGRP) is a polypeptide produced by alternative processing of calcitonin gene transcripts and is endowed with important systemic physiological effects. The recent characterization of its receptor and the discovery of stable antagonists has addressed them in the indication migraine. Beside this, several studies have been focused on role of CGRP at gastric level. CGRP is considered a marker of afferent fibers in the upper gastrointestinal tract being almost completely depleted following treatment with the selective neurotoxin capsaicin that targets these fibers via transient receptor poten...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Evangelista S Tags: Curr Pharm Des Source Type: journals

Fibroblast growth factor-2 antagonist and antiangiogenic activity of long-pentraxin 3-derived synthetic peptides.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Angiogenesis and inflammation are closely integrated processes. Fibroblast growth factor-2 (FGF2) is a prototypic angiogenesis inducer belonging to the family of the heparin-binding FGF growth factors. FGF2 exerts its pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. A tight cross-talk exists between FGF2 and the inflammatory response in the modulation of blood vessel growth. Pentraxins act as soluble pattern recognition receptors with a wide range of functions in various pathophysiological condition...
Source: Current Pharmaceutical Design - October 29, 2009 Category: Drugs & Pharmacology Authors: Leali D, Alessi P, Coltrini D, Rusnati M, Zetta L, Presta M Tags: Curr Pharm Des Source Type: journals

Pharmacogenetics in Psychiatry - A Useful Clinical Tool or Wishful Thinking for the Future?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
More than fifty years of pharmacogenetic research have produced many examples of the impact of inherited variability in the response to psychotropic drugs. These successes, however, have as yet failed to translate into broadly applicable strategies for the improvement of individual drug treatment in psychiatry. One important argument against the widespread adoption of pharmacogenetics as a clinical tool is the lack of evidence showing its impact on medical decision making and on risk benefit ratio for the patients. The individual drug metabolizing capacity is assessed by genotyping drug metabolizing enzymes. The potent...
Source: Current Pharmaceutical Design - October 14, 2009 Category: Drugs & Pharmacology Authors: Kirchheiner J, Seeringer A, Viviani R Tags: Curr Pharm Des Source Type: journals

Pharmacogenetics in Oncology: A Promising Field.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Pharmacogenetics is a rapidly developing field, especially in oncology. In the most ideal situation pharmacogenetics will allow oncologists to individualize therapy based on patients' individual germline genetic test results. This can help to improve efficacy, reduce toxicity and predict non-responders in a way that alternative therapy can be chosen or individual dose adjustments can be made. Multiple pathways have been studied extensively of which a brief review is presented here. Increased 5FU toxicity is associated with variations in the DPYD gene, TYMS gene and MTHFR gene. Furthermore variations in the UGT1A gene a...
Source: Current Pharmaceutical Design - October 14, 2009 Category: Drugs & Pharmacology Authors: Houtsma D, Guchelaar HJ, Gelderblom H Tags: Curr Pharm Des Source Type: journals

Ethical and Social Issues in Pharmacogenomics Testing.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In genomics research, pathways that lead to disease and the role of drugs in these pathways are being unravelled at a high rate. In this paper ethical and social challenges related to pharmacogenomics research are discussed as well as clinical applications. In research, ethical thinking evolves due to the fast pace of research. Genome-wide association studies trying to identify genes that contribute a small risk to common diseases can only be performed on an international scale. Meanwhile, it is becoming more and more clear that genomic information is hard to hide. Thus the traditional promise in research that privacy ...
Source: Current Pharmaceutical Design - October 14, 2009 Category: Drugs & Pharmacology Authors: Vijverberg SJ, Pieters T, Cornel MC Tags: Curr Pharm Des Source Type: journals

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Curr Pharm Des. 2009 Oct 15; Authors: Franke RM, Gardner ER, Sparreboom A During the last decade, a greater focus has been given to impact of genetic variation in membrane transporters on the pharmacokinetics and toxicity of numerous therapeutic drugs. While the majority of transporter-related pharmacogenetic research has been in regards to classic genes encoding the outward-directed ATP-binding cassette (ABC) transporters, such as ABCB1 (Pglycoprotein), ABCC2 (MRP2), and ABCG2 (BCRP), more studies have been conducted in recent years evaluating genes encoding solute carriers (SLC) that mediate the cellular uptake o...
Source: Current Pharmaceutical Design - October 14, 2009 Category: Drugs & Pharmacology Authors: Franke RM, Gardner ER, Sparreboom A Tags: Curr Pharm Des Source Type: journals

Pharmacogenetics of Thiopurines in Inflammatory Bowel Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Thiopurines are widely used in the treatment of inflammatory bowel disease (IBD). However, in clinical practice azathioprine (AZA) or 6-mercaptopurine (6-MP) are not effective in one-third of patients and up to one-fifth of patients discontinue thiopurine therapy due to adverse reactions. The observed interindividual differences in therapeutic response and toxicity to thiopurines are explained to a large extent by the variable formation of active metabolites, which is at least partly caused by genetic polymorphisms of the genes encoding crucial enzymes in thiopurine metabolism. In this in-depth review we discuss the ge...
Source: Current Pharmaceutical Design - October 14, 2009 Category: Drugs & Pharmacology Authors: Derijks LJ, Wong DR Tags: Curr Pharm Des Source Type: journals

Pharmacogenetics and the Pharmaceutical Industry.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The detailed knowledge of the human genome has not fulfilled its promise as yet. It seems fair to say that we are far from treating existing diseases by therapeutic interventions developed on the basis of genetic knowledge. However, pharmacogenetics has shown to be useful in improving our understanding of pharmacotherapy. Industry is starting to embed this knowledge in the design of innovative drugs and there are three important areas of interest: safety, efficacy and target identification. Application of pharmacogenetics e.g. in patient selection are leading to the direction of more personalised medicine. The future w...
Source: Current Pharmaceutical Design - October 14, 2009 Category: Drugs & Pharmacology Authors: Raaijmakers JA, Koster ES, Maitland-van der Zee AH Tags: Curr Pharm Des Source Type: journals

Individualizing Calcineurin Inhibitor Therapy in Renal Transplantation - Current Limitations and Perspectives.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Patient variability in clinical response to the calcineurin inhibitors (CNIs) cyclosporine A and tacrolimus partly results from differences in CNI exposure. For tacrolimus drug interactions and genetic variability relate to tacrolimus exposure. Patients carrying the CYP3A5*1 allele have an increased tacrolimus metabolism, hence lower drug exposure. Adjusting the tacrolimus dose to this genotype is a tool to optimize therapy from a pharmacokinetic perspective. In contrast, no genetic variants have been found to clearly relate to cyclosporine A exposure. Despite therapeutic drug monitoring aimed at individualizing CNI th...
Source: Current Pharmaceutical Design - October 14, 2009 Category: Drugs & Pharmacology Authors: Press RR, de Fijter JW, Guchelaar HJ Tags: Curr Pharm Des Source Type: journals

Pharmacogenetics in Treatment of Rheumatoid Arthritis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Over the last decades important progress is being made regarding disease modifying anti-rheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis (RA). Nevertheless, a substantial part of the patients fail to achieve a good response and/or experience toxicity, which limits further treatment leading to progression of inflammation and destruction of joints. These high interindividual differences in drug response gave rise to the need for prognostic markers in order to individualize and optimize therapy with these antirheumatic agents. Besides demographic and clinical factors, studies in the research field of phar...
Source: Current Pharmaceutical Design - October 14, 2009 Category: Drugs & Pharmacology Authors: Kooloos WM, Huizinga TW, Guchelaar HJ, Wessels JA Tags: Curr Pharm Des Source Type: journals

Pharmacogenetics of Oral Anticoagulant Therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The identification of the genes encoding CYP2C9, the principal metabolizing enzyme of the coumarins, and VKORC1, the molecular target for coumarins, has strongly stimulated the research on pharmacogenetics of vitamin K antagonists, also designated as coumarins. From 1999 to 2004 a number of observational studies firmly established associations between being carrier of the CYP2C9*2 and especially the CYP2C9*3 allele and reduced coumarin dose requirements and increased risks of overanticoagulation and even major bleeding compared to CYP2C9 wild type patients. The identification of the VKORC1 gene in 2004 gave rise to mor...
Source: Current Pharmaceutical Design - October 14, 2009 Category: Drugs & Pharmacology Authors: Schalekamp T, de Boer A Tags: Curr Pharm Des Source Type: journals

Pharmacogenetics of Phase I and Phase II Drug Metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Genetic variation in the receptors and other intracellular targets that mediate the pharmacodynamic effects of drugs can affect therapeutic outcomes. However, at present greater knowledge is available concerning the extent of gene variation in drug metabolizing enzymes that determine drug pharmacokinetics and, in turn, drug efficacy and toxicity. Information on the incidence of polymorphisms in the cytochrome P450 (CYP) genes that mediate phase I biotransformation is increasing, although the level of detail in the case of phase II conjugation enzymes, such as the UDP-glucuronosyltransferases (UGTs) and N-acetyltransfer...
Source: Current Pharmaceutical Design - October 14, 2009 Category: Drugs & Pharmacology Authors: Crettol S, Petrovic N, Murraya M Tags: Curr Pharm Des Source Type: journals