Neuropharmacology

Biography

Biography: Arjan Blokland

Abstract

Many factors can complicate the translation from animal studies to human studies, especially relating to the development of cognition enhancers. First, models that are being used in animal experiments have a poor validity (e.g., construct validity). This relates to the deficit model that should reflect a disease model. Since these models can only mimic a specific aspect of a complex disease state it is not surprising that these models can only have a limited value when evaluating novel drugs. As a second factor, the face validity of animal test models is obviously rather poor when comparing these with memory tasks in humans. It is well known that there are species differences in PK/PD parameters, which is a third complicating factor. For example, the absorbtion of brain penetration is much faster in animals as compared to humans. It is known that this difference can have a different effct on brain functions. A fourth complicating factor may be related to the inverted U-shape of dose-related effects of CNS drugs. This further complicates dose finding and titraing the effective dose for human studies on basis of animal data. A final factor that should be considered is the animal itself. In most studies animals are used that are not raised in an enriched environment, as is the case in humans. A recent study shows that effects of a drug improved memory performance in standard housed but not in animals in an enriched environment. We need to better understand and control these different factors before we can improve translational models for cognition-enhancing drugs.