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Psychopharmacological strategies in the search for cognition enhancers
1Laboratoires d'Etudes et de Recherches Synthélabo, Bagneux, France.
Abstract:
In order to discover and develop drugs to treat cognitive decline, animal tests are needed which will predict clinical activity. The process of developing such animal models does not differ, in principle, from the approaches used in other areas of psychotropic drug research. One research approach involves attempts to create models homologous with the disorder to be treated. This requires a thorough analysis of the clinical problem and an attempt to reproduce the biological and behavioral aspects of the disorder in animals. Recent studies of the effects of certain brain lesions on learning in monkeys or rats as models of Alzheimer's disease may go some way towards developing an animal model for this disorder. However, it is arguable whether this approach to "modelling" has ever had much success in psychopharmacology. A more pragmatic strategy involves the development of what are sometimes called emperical models, according to which any biological and behavioral test can be used if it provides a reasonable prediction of activity in the clinic. For example, the much used passive avoidance test in rodents does not need to model human cognition if it accurately predicts clinical activity. The extent to which this approach can be used successfully for evaluating cognition-enhancing drugs is discussed in view of the many drugs already marketed as cognition enhancers.
Insights
Developing animal models for cognitive decline drug discovery requires either homologous or empirical approaches. Empirical models, predicting clinical activity, are often more pragmatic for identifying effective cognition-enhancing drugs.
Area of Science:
- Neuroscience
- Pharmacology
- Drug Discovery
Background:
- Developing drugs for cognitive decline necessitates reliable animal testing to predict clinical efficacy.
- Current drug research methodologies for psychotropic substances are applicable to cognitive disorder models.
Purpose of the Study:
- To explore strategies for developing predictive animal models for cognitive decline drug discovery.
- To evaluate the success of homologous versus empirical modeling approaches in psychopharmacology.
Main Methods:
- Analysis of homologous modeling strategies, including replicating Alzheimer's disease aspects in rodents and monkeys.
- Examination of empirical modeling, utilizing tests like passive avoidance in rodents for predicting clinical activity.
Main Results:
- Homologous models, while aiming for direct disease replication, have questionable success in psychopharmacology.
- Empirical models demonstrate potential utility if they accurately predict clinical drug activity, irrespective of direct disease homology.
Conclusions:
- The pragmatic approach of empirical modeling offers a viable strategy for identifying cognition-enhancing drugs.
- The effectiveness of empirical tests in predicting clinical outcomes for cognition enhancers warrants further investigation given existing marketed drugs.