TABLE 9

Inhibition of horse liver alcohol dehydrogenase by a competitive (ADP) and a noncompetitive (o-phenanthrolene) inhibitors The fractional inhibitions (fi) of the horse liver alcohol dehydrogenase reaction were measured in the presence of I1, ADP, and/or I2, o-phenanthrolene. These fi values were retrieved from the graph of experimental observations by Yonetani and Theorell (1964; Fig. 3E). These data were used as an example to check the median-effect principle and the multiple drug effect equation earlier (Chou and Talalay, 1981) before the computer software became available and before the term combination index was introduced. The computerized analyses of these data with CompuSyn are given in the table with full or partial data and with constant ratio and nonconstant ratio analysis. Some combinations (i.e., in diagonal [1]-[5]) are in constant ratio (1:17.4) and some (i.e., in two triangles) are in nonconstant ratios [for CompuSyn printout, see Supplemental Data Appendix III (http://pharmrev.aspetjournals.org/cgi/content/full/pr.58.3.10/DC1)]. These full and partial analyses yield nearly identical synergistic conclusions. Modified from “Studies on Liver Alcohol Hydrogenase Complexes. 3. Multiple Inhibition Kinetics in the Presence of Two Competitive Inhibitors,” Archives of Biochemistry and Biophysics, volume 106, pp 243-251. Copyright 1964 with permission from Elsevier.

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