Do epinephrine and norepinephrine exist in the body as a racemic mixture? How does the chirality of the compound affect the receptors? Do s-norepinephrine and r-norepinephrine function the same in the human body?

Natural epinephrine is (##R##)-(-)-epinephrine, and natural norepinephrine is (##R##)-(-)-norepinephrine.

The drugs, however, are often supplied as racemic mixtures.

According to theory, the chiral molecule interacts with three sites on the receptor.

• an anionic site for the ammonium ion
• a hydrogen-bonding site for the β-hydroxyl group
• a flat site for π-π interaction with the aromatic ring

(from tigger.uic.edu)

The less active isomer can establish only a two-point contact.

This loss of the H-bonding interaction equals about 12 kJ/mol, and this corresponds to a 100-fold decrease in activity.

The only difference between epinephrine and norepinephrine is that the latter lacks an N-methyl group.

This does not affect the three-point connection to the receptor.

(##S##)-Norepinephrine and (##R##)-norepinephrine have the same function in the body, but the (##R##) isomer is more effective.