Stereochemistry is extremely important on the way a drug will behave. Chirality is a branch of stereochemistry and is defined as the ability to superimpose (or not) on its mirror image. If it’s mirror image is distinguishable or cannot be superimposed than the molecule is considered chiral. This is important because a chiral molecule has two forms(R, S) that are extremely similar and only differing in their mirror image1. Ultimately this becomes extremely important because certain drugs will be in one enantiomer or the other and one enantiomer may be more effective than its counterpart2. In fact the difference is so great, that two enantiomers of the same molecule should be considered two different drugs altogether.
The drastic difference in effectiveness of chemical (drug) enantiomers is due to the eventual binding site of this particular chemical. The binding site will align perfectly with a particular enantiomer, however if the wrong enantiomer is used then it will not be able to bind thus eliminating its effectiveness2. Other differences that have an impact on the enantiomers effectiveness include the bioavailability, rate of metabolism, metabolites, excretion, potency and selectivity for receptors, transporters and/or enzymes, and toxicity2.
One example of a specific drugs enantiomer differences can be illustrated by citalopram, the S-enantiomer is primarily responsible for antagonism of serotonin reuptake while the R-enantiomer is 30-fold less potent3. Clinical trials have been conducted on this particular drug to try to understand the differences. The trials results has shown that (S)-citalopram has greater efficacy than (R,S)-citalopram at doses predicted to be equivalent as well as equal efficacy to (R,S)-citalopram at a dose that produces fewer side effects4,5.
Another such drug is fluoxetine, a depression drug, this drug has shown that bothe enantiomers are effective at blocking serotonin re-uptake, the way they break down in the body is different6. The ‘R’ form of this drug led to serious heart problems and cannot be given to patients for safety concerns, while the ‘S’ form is safe and effective.
Another such drug that has vastly different effects for specific enantiomers is mianserin, a antidepressant. The S enantiomer is more potent in antidepressant screens, and has been shown to be more active in a number of different