Eudysmic ratio

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

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 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]

An equal mixture of both enantiomers is called racemate, which may be easier to manufacture than a single enatiomeric form.

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. Alternatively, it is possible that the distomer converts in the body into the eutomer, at least partly.

Calculation

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.[4][5] Whether one chooses to use the EC50 or IC50 depends on the drug in question.

Examples

See also

References

  1. Wermuth, CG; Ganellin, CR; Lindber, P; Mitscher, LA (1998). "Glossary of Terms used in Medicinal Chemistry (IUPAC Recommendations 1998)". Pure & Appl. Chem. 70: 1129–1143. doi:10.1351/pac199870051129.
  2. Hermann J. Roth, Christa E. Müller, Gerd Folkers: Stereochemie und Arzneistoffe, Wissenschaftliche Verlagsgesellschaft Stuttgart, 1998, S. 80−82, ISBN 3-8047-1485-4.
  3. E. J. Ariëns (1984). "Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology". Eur. J. Clin. Pharmacol. 26 (6): 663–668. doi:10.1007/bf00541922. PMID 6092093.
  4. Lehmann, F.P.A.; Rodriques de Miranda, J.F.; Ariëns, E.J. (1978). "Stereoselectivity and affinity in molecular pharmacology. III. Structural aspects in the mode of action of natural and synthetic auxins". Chem Biol Interact. 20 (2): 101–142. PMID 647843.
  5. Ariëns, E.J. (1991). "Racemic therapeutics - ethical and regulatory aspects". Eur J Clin Pharmacol. 41 (2): 89–93. doi:10.1007/BF00265897. PMID 1743252.
This article is issued from Wikipedia - version of the Monday, April 25, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.