Biomedical Engineering Reference
In-Depth Information
5.4.1 T
HE
D
ISTOMER
I
S
I
NACTIVE
(H
IGH
ER)
In this case the distomer is either inactive or displays no undesirable side effects. In the case of the
antihypertensive agent (b-blocker) propranolol (Figure 5.6) the (
S
)-enantiomer is 130-fold more
potent than the (
R
) enantiomer as a b-adrenoceptor antagonist (i.e., ER = 130). A number of other
b-blockers based on this structure show high ERs. These drugs are therefore marketed as racemates
as the distomer displays no side effects. Despite this there would have been advantages in marketing
the (
S
)-enantiomer if only to extend patent life.
N
H
N
H
O
O
OH
OH
(
S
)-Propranolol (eutomer, ER = 130)
(
R
)
-
Propranolol
(distomer)
FIGURE 5.6
The ER for (
S
)- and (
R
)-propranolol is 130.
5.4.2 B
OTH
E
NANTIOMERS
H
AVE
I
NDEPENDENT
T
HERAPEUTIC
B
ENEFITS
In some instances, both enantiomers of a drug may have different therapeutic values. The classical
example of this behavior is the diastereomers quinine and quinidine (Figure 5.7). Quinine, which
was originally obtained from the bark of cinchona trees was, for centuries, the only treatment for
malaria. Quinidine, on the other hand, is used as a class 1A antiarrhythmic agent and acts by
increasing action potential duration.
OMe
OMe
N
OH
N
OH
N
N
Quinine (antimalarial)
Quinidine (antiarrhythmic)
O
O
H
H
H
3
C
CH
3
O
O
N
N
DARVON
(analgesic)
NOVRAD
(antitussive)
FIGURE 5.7
Examples of drugs where both stereoisomers possess therapeutic benei ts.
