Eudysmic ratio

The eudysmic ratio (also spelled eudismic ratio) is a common term in pharmacology, chemistry, and molecular biology. The eudysmic ratio describes the difference in pharmacologic activity between the two enantiomers of a drug.

When enantiomers are formed non-selectively and the resulting product contains an equal quantity of each enantiomer it is called a racemic mixture.

In pharmacology it is frequently, though not always, the case that one enantiomer of a chiral drug has greater pharmacological activity than the other. The eudysmic ratio is a mathematical equation that quantitatively measures the difference in this activity. A eudysmic ratio significantly differing from 1 means that there is a large difference in activity between the two enantiomers.

Terminology

The eutomer is the chiral enantiomer having the desired pharmacological activity,^[1] e.g., as an active ingredient in a drug.

The distomer, on the other hand, is the enantiomer of the eutomer which may have undesired bioactivity or may be bio-inert.^[2]

It is often the case that only a single one of the enantiomers contains all of the wanted bioactivity, the distomer is often less active, has no desired activity or may even be toxic.^[3] In some cases the eudysmic ratio is so high that it is desired to separate out the two enantiomers instead of leaving it as a racemic product. It is also possible that the distomer is not simply completely inactive but actually antagonizes the effects of the eutomer.

Calculation

The sum of the difference between the more active substance, the eutomer, and the less active substance, the distomer, is called the eudysmic ratio. One way the eudysmic ratio is computed is by dividing the EC50 or the IC50 of the distomer by the same measurement of the eutomer. Whether one chooses to use the EC50 or IC50 depends on the drug in question.

Examples

• Citalopram is a case example of such a compound, and steps were taken to separate out the weaker enantiomer.
• Thalidomide is a drug whose two enantiomers cause distinctly different effects from one another. This is an example where the two enantiomers of a drug have different pharmacologic effects.
• Amino acids are also a very interesting example of eudysmic ratio. Nearly all of the amino acids in the human body are called "L" amino acids; despite being chiral, the body almost exclusively creates and uses amino acids in this one configuration. D amino acids, the enantiomers - or "mirror images" - of the amino acids in the human body cannot be incorporated into proteins. D-aspartate and D-serine are two notable counterexamples, since they do not appear to ever be incorporated into proteins, but instead act individually as signalling molecules. However, mammals can metabolize significant amount of D amino acids by oxidizing them to alpha-ketoacids (most of which are non-chiral) and then transaminases can create L amino acids. There are no reasons to believe that humans are exceptional, they have all required enzymes (DDO, DAO). Some common foods contain near-racemic mixtures of amino acids.

References