Core Battery CNS Studies

The present Section describes basic protocols satisfying ICH S7A recommendations for core battery CNS studies. Included are protocols for measuring general behavioral signs induced by test substances (Irwin Test), effects on spontaneous locomotion (Activity Meter Test), effects on neuromuscular coordination (Rotarod Test), effects on the convulsive threshold (Electroconvulsive Shock (ECS) Threshold and PTZ Seizure Tests), interaction with hypnotics (Barbital Interaction Test) and effects on the pain threshold (Hot Plate Test). 

Core battery CNS procedures are by design simple tests, using very traditional techniques, which can be carried out rapidly in a routine and objective fashion. They are the first techniques to be employed in safety assessment and are frequently applied at the very beginning of the discovery process as a screen to eliminate substances with a potential for CNS risk. Because of their use early in the safety evaluation process, such studies are conducted most usually in the rat or the mouse, diough (as we shall see) analogous methods have been developed and validated and are in use with dogs, primates, and pigs. 

Issues of cardiovascular safety have brought safety pharmacology to the forefront, especially with issues like prolongation of the QTc interval. In the United States, IND s must routinely include the core battery of cardiovascular, CNS, and pulmonary function studies. The reader is referred to Chapter 13 for a thorough discussion of this important topic. 

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... 

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