Drug-Receptor Interaction IV

Enantioselectivity of Drug Action
Many drugs are racemates, including !-
blockers, nonsteroidal anti-inflammatory
agents, and anticholinergics (e.g.,
benzetimide A). A racemate consists of
a molecule and its corresponding mirror
image which, like the left and right
hand, cannot be superimposed. Such
chiral (“handed”) pairs of molecules are
referred to as enantiomers. Usually,
chirality is due to a carbon atom
linked to four different substituents
(“asymmetric center”). Enantiomerism is
a special case of stereoisomerism. Nonchiral
stereoisomers are called diastereomers
(e.g., quinidine/quinine).
Bond lengths in enantiomers, but
not in diastereomers, are the same.
Therefore, enantiomers possess similar
physicochemical properties (e.g., solubility,
melting point) and both forms are
usually obtained in equal amounts by
chemical synthesis. As a result of enzymatic
activity, however, only one of the
enantiomers is usually found in nature.
In solution, enantiomers rotate the
wave plane of linearly polarized light
in opposite directions; hence they are
refered to as “dextro”- or “levo-rotatory”,
designated by the prefixes d or (+) and l
or (-), respectively. The direction of rotation
gives no clue concerning the spatial
structure of enantiomers. The absolute
configuration, as determined by
certain rules, is described by the prefixes
S and R. In some compounds, designation
as the D- and L-form is possible
by reference to the structure of D- and
L-glyceraldehyde.
For drugs to exert biological actions,
contact with reaction partners in
the body is required. When the reaction
favors one of the enantiomers, enantioselectivity
is observed.