Eudismic index

The more active isomer (where activity refers to binding affinity at a defined receptor) is designated the eutomer, the less active is the distomer. The ratio of activities is the eudismic ratio, and its logarithm, the eudismic index, is then proportional to the difference in binding free energy between the enantiomers. The eudismic index is a quantitative measure of chiral discrimination. 

Figure 6. pA2 (pKj) and ApA2 (ApKj) values of the enantiomers of compounds 8 and 9 as well as of related achiral compounds 8a, 8b, 9a and 9b at muscarinic Mj (rabbit vas deferens), M2 (guinea-pig atria) and M3 receptors (guinea-pig ileum) Ph = Phenyl c-Hex = Cylohexyl E.I. = Eudismic index. 

Table 17.1 Differences in activity or in affinity (eudismic index) between couples of enantiomers...

Eudismic quotient Affin-Sit/Affin-Dw Eudismic index (El) Log Affin-En-Log Affin.Dij... 

A summary of these data on monoamine uptake inhibition and on inhibition of binding by rat brain synaptosomes of the selective 5-HT uptake inhibitor paroxetine and the selective NE uptake inhibitor tomoxetine taken from [53] is shown in table 5. Although the eudismic ratio (potency less active isomer/potency active isomer) of the R and S isomers of fluoxetine is fairly dose to one i.e. 1.58, the selectivity index (antilog (pl 5-HT - Pkj NE) of the S isomer is much larger than that of the R isomer. In offier words the R isomer of fluoxetine is a less selective 5-HT uptake inhibitor than the S isomer but their potendes are similar. This is also confirmed by the data on the inhibition of H-paroxetine and H-tomoxetine binding. 

The eudismic ratio of the R- and S isomer for the inhibition of %-paroxetine is one, so their potencies are the same. However, the selectivity index for the inhibition of H-paroxetine and %[-tomoxetine binding is 24 for the R isomer and 155 for the S isomer of fluoxetine indicating that the R isomer is less selective than the S isomer in regard to the afflnily of the compounds for the 5-HT tremsporter versus the NE transporter. 

The activity of the racemic trans ( ) compound in vitro as well as in vivo is caused by McN 5652-Z its trans (+) enantiomer as the trans (-) enantiomer is comparatively inactive. The eudismic ratio for 5-HT uptake inhibition (Kj trans (-) / K trans (+)) is 150 and for NE uptake inhibition 155. The selectivity index of the trans (+) isomer for 5-HT upteike inhibition versus NE uptake inhibition (K NE / Kj 5-HT) is a moderate 4.6. 

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