Current Pharmaceutical Design - Volume 16, Issue 5, 2010

Schizophrenia is a chronic, severe, and disabling brain disorder characterized by a profound disruption of perception, cognition, and emotion. The condition affects approximately 1% of the population and is thought to be the result of genetic vulnerability and environmental influences. The symptoms of schizophrenia fall into three main categories, i.e. positive symptoms (hallucinations, delusions), negative symptoms (apath Read More

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 Read More

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 Read More

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. The potential use of 5-HT1A receptor agonism is emerging as one potential area that could be exploited to improve clinical management of t Read More

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 sy Read More

The most abundant homomeric nicotinic acetylcholine receptors (nAChRs) in the mammalian brain are the pentameric α7 nAChRs which consist of five α7 subunits, and each subunit provides an orthosteric low affinity binding site for its endogenous ligand, acetylcholine. Distribution and high level expression of α7 nAChRs within the limbic circuitry, including the hippocampus and prefrontal cortical areas are in line with their in Read More

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, p Read More

The case for peptide-based drugs is compelling. Due to their chemical, physical and conformational diversity, and relatively unproblematic toxicity and immunogenicity, peptides represent excellent starting material for drug discovery. Nature has solved many physiological and pharmacological problems through the use of peptides, polypeptides and proteins. If nature could solve such a diversity of challenging biological problem Read More