Which thalidomide isomer is harmful?
Thalidomide exists in two mirror-image forms: it is a racemic mixture of (R)- and (S)-enantiomers. The (R)-enantiomer, shown in the figure, has sedative effects, whereas the (S)-isomer is teratogenic.
Why are enantiomers important in pharmaceuticals?
Despite this knowledge, many drugs are administered as their racemates. Manipulation of the enantiomeric ratio or the use of only one enantiomer of a drug may allow separation of toxicity and efficacy, and this may lead to a significant increase in therapeutic ratio and a more rational approach to therapeutics.
What are the effects of stereochemistry on drug action?
The use of single-enantiomer drugs can potentially lead to simpler and more selective pharmacologic profiles, improved therapeutic indices, simpler pharmacokinetics due to different rates of metabolism of the different enantiomers, and decreased drug interactions.
Are most drugs chiral?
Chemical compounds that come as mirror-image pairs are referred to by chemists as chiral or handed molecules. Each twin is called an enantiomer. Drugs that exhibit handedness are referred to as chiral drugs….Thalidomide.
| Chiral drug | Ketamine |
|---|---|
| Chiral centers | 1 |
| Clinical effects | Anesthetic |
| Hallucinogen |
What enantiomer causes birth defects?
The (R)-enantiomer is an effective sedative medication and the (S)-enantiomer may be teratogenic. (S)-Thalidomide was shown to be responsible for over 2000 cases of birth defects in children born to women who took the drug during pregnancy (Figure 6) (see Chapters 1.4 and 1.8).
Why is thalidomide toxic?
They conclude that this is because the embryos core blood vessels were suitably developed at the time, but the limbs had not yet acquired an adequate blood supply. This paper therefore puts the ability of thalidomide to block the development of new blood vessels as the most likely cause of its side effects.
Why do we separate enantiomers?
Because they are mirror images, each enantiomer rotates plane-polarized light in an equal but opposite direction and is optically inactive. If the enantiomers are separated, the mixture is said to have been resolved.
Why do we need stereochemistry?
Using stereochemistry, chemists can work out the relationships between different molecules that are made up from the same atoms. They can also study the effect on the physical or biological properties these relationships give molecules. An important part of stereochemistry is the study of chiral molecules.
Is ibuprofen chiral?
As is the case with numerous other drugs, Ibuprofen is a chiral compound. The human body with its numerous homochiral compounds will interact with each racemic drug differently and metabolize each enantiomer by a separate pathway to generate a different pharmacokinetic and pharmacodynamic activity.
What was the thalidomide tragedy?
In November 1961, thalidomide was taken off the market due to massive pressure from the press and public. Experts estimate that thalidomide led to the death of approximately 2,000 children and serious birth defects in more than 10,000 children, about 5,000 of them in West Germany.