Current Pharmaceutical Design - Volume 12, Issue 20, 2006

In modern society the market for drugs to enhance human performance is large. Health-food stores and Internet sites already offer a large variety of ‘smart drugs’ or ‘nootropics’ that are claimed to improve intelligence in humans of all age categories. Such products usually include multivitamins or herbal extracts from ginseng, ginko biloba or other substances derived from non-Western cultures. Most of these claims Read More

The performance- and alertness-sustaining/restoring effects of modafinil during sleep deprivation in normal, healthy adults were reviewed. Results indicate that modafinil is efficacious for sustaining/restoring objective performance and alertness during sleep deprivation with few adverse effects. At appropriate dosages, modafinil restores performance and alertness to non-sleep deprived levels. Modafinil also impairs post-sleep de Read More

In the past decade, experimental studies involving healthy human volunteers have revealed that manipulations of the central serotonin (5-HT) system can produce quite specific changes in cognitive functioning, independent of overt mood changes. Reduced 5-HT turnover is consistently associated with impaired long-term memory functioning. Low 5- HT function may also impair cognitive flexibility and improve focused at Read More

The ascending dopamine system of the mammalian brain has been associated with motor, mnemonic and goaldirected or reward-related behaviour. The most progress in understanding the cortical mechanisms of dopaminergic modulation of function has been made with regards to short-term mnemonic (or working memory) function. Research in experimental animals strongly suggests that stimulation of dopamine Read More

Whereas antihistamines are generally known for their sedative side effects, this review shows that several studies also found mild stimulating effects on performance for the H1-antagonists terfenadine, ebastine, fexofenadine and desloratadine. These stimulating effects were mostly demonstrated in tasks involving high levels of attention, e.g. divided attention tasks, vigilance tasks and driving tasks. The stimulating eff Read More

During the last decennia, our understanding of the neurobiological processes underlying learning and memory has continuously improved, leading to the identification of targets for the development of memory-enhancing drugs. Here we review a class of drugs which has more recently been identified: the phosphodiesterase (PDE) inhibitors. An overview is given of the different PDEs that are known and we focus on three PDEs Read More

In this article cognition assessments as outcome measures in CNS drug development research are described. An outline is given of the various choices that can be made and the reasons for them, depending on the approach followed. First, a brief historical context is provided of the psychological sciences that have contributed to today's psychopharmacology of cognition assessment. Subsequently, the focus is on ide Read More

The appropriate functioning of living organisms depends upon the correct performance and inter-relationship of different organs and tissues. Cells are the basic units of tissues and their proper function depends upon a network of thousand of proteins, each of which plays an important and specific role. The biological function of a protein depends on its threedimensional structure, which is determined by its amino acid seque Read More

Polyglutamine diseases are autosomal dominant, late-onset neurodegenerative disorders. Expansion of a polyglutamine (polyQ) tract above a threshold size leads to misfolding and aggregation and eventual intracellular accumulation of the disease-specific protein. To date, only symptomatic treatments of limited effectiveness are available. Various research strategies aim to interfere with known steps in the path Read More

Several human diseases are associated with the presence of toxic fibrillar protein deposits. These diseases called protein misfolding disorders, are characterized by the accumulation of misfolded protein aggregates in diverse tissues. Strong evidence indicates that the conversion of a normal soluble protein into a β-sheet-rich oligomeric structure and further fibrillar aggregation are the key events in the disease pathogenesis. Read More

The seminal finding that immunization with amyloid-β 1-42 in Alzheimer's disease (AD) mouse model prevented formation of and/or cleared amyloid plaques has led to numerous studies exploring related approaches for AD and other conformational degenerative disorders. While clinical trials in AD patients were discouraging because of serious side effects, this approach remains promising in light of recent findings in ani Read More

Prion diseases are fatal neurodegenerative disorders associated with conformational conversion of the cellular prion protein (PrPC) into an isoform designated PrPSc. The pathogenic mechanism that links this conformational distortion with the development of prion diseases is unknown. PrPC is a GPI-anchored cell surface protein that associates with lipid rafts, undergoes endocytosis and recycles. Although the physiological functio Read More