Supplementary CNS Studies

Supplementary CNS safety studies are more complex procedures, investigating test substance effects on cognitive processes, electrophysiological brain activity or their potential to cause drug-dependence/abuse. The following Section is therefore divided into three sub-sections dealing with these different areas. As for the core battery studies described above, an essential... 

For supplementary studies, the rat remains the species of choice. A possible exception is the use of primates for assessment of abuse potential. The reason is not that drug effects differ between the species, but more because primates are closer to man in terms of active doses and pharmacokinetics, thereby increasing predictability in areas of more complex CNS function. 

H, CHj, NHz, OH, 0CH3, F, NO2, CN, CHO, CF3, Li, O", NH, and NH3" ). Some of the work reported herein has been previously published (6,8-11) but a large part of our discussion refers to previously unpublished data accumulated over a number of years from several different laboratories. The primary goal of this study has been to draw together this wide body of computational data and to attempt to understand the diverse behavior observed within a relatively simple PMO (7) framework. There are undoubtedly other frameworks within which the results could be analyzed and we make no claim that our interpretation is necessarily unique. However, regardless of the qualitative picture of substituent effects which we develop here, the quantitative data stand on their own and hopefully may be utilized by other workers to prove or disprove alternative or supplementary hypotheses concerning substituent effects in aromatic systems. 

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