Figure 1.

Cytochrome c release from purified mitochondria is differentially affected by the various compounds in the NINDS library. A, This distribution is constructed from measurements of the impact of each drug on cytochrome c release. Data are gathered on 80 compounds (i.e., the entire complement of kit 6). The x-coordinate in this graph is a measure of cytochrome c release from Ca²⁺-stimulated mitochondria. The x-axis is divided into intervals, 20 of them per 1 ng/ml change. The y-coordinate is the number of events falling into each such bin. The green line marks the level of cytochrome c release upon stimulation with Ca²⁺ ions but in the absence of other pharmacological agents. Compounds scored to the right of the green line stimulate cytochrome c release; those scored to its left are inhibitory of the process. The blue line corresponds to the level of cytochrome c release in the absence of Ca²⁺ ions. The red line is the level of Ca²⁺-stimulated mitochondria in the presence of cyclosporin A. B, Colored curves are equivalent distributions for each of the 13 kits. Measurements within each set of compounds are normalized, thereby generating distributions with identical mean values. The black line is the sum of these 13 distributions. The dotted line is 1.5 SDs less than the mean value for the grand distribution. The x-axis is again divided into intervals, each of which spans 1/20 of the unit distance from zero to the normalized mean. The y-coordinate is the number of measurements among all 1040 that fall into the interval in question. C, After ranking the compounds for their effectiveness at inhibiting cytochrome c release, 21 of them are selected. Not only do these potentially therapeutic molecules strongly affect the test mitochondria, they are known to cross the blood–brain barrier and can be safely administered to patients. All are in clinical usage, each one in the indicated capacity. NCC, National Institute of Neurological Disorders and Stroke Custom Collection.