Biomedical Engineering Reference
In-Depth Information
OH
(+)-Dobutamine -
β
-adrenoceptor agonist
α
-adrenoceptor antagonist
N
HO
CH
3
HO
(-)-Dobutamine -
β
-adrenoceptor agonist
α
-adrenoceptor agonist
CF
3
COOCH
3
CF
3
COOCH
3
O
2
N
O
2
N
H
H
(
S
)-BayK8644
(activator of
L
-type Ca
2+
channel)
(
R
)-BayK8644
(antagonist of
L
-type Ca
2+
channel)
FIGURE 5.9
Examples of drugs where the eutomer and the distomer have the opposite biological activity.
H
H
H
2
N
CO
2
H
HO
2
C
NH
2
CO
2
H
CO
2
H
CO
2
H
CO
2
H
(
R
)-DCPG
AMPA receptor antagonist
no efect on mGlu8
(
S
)-DCPG
No efect on AMPA receptor
mGlu8 receptor agonist
FIGURE 5.10
Both (
R
)- and (
S
)-3, 4-DCPG have potential therapeutic value. However, the racemate is more
potent as an antiepileptic agent.
the (
S
)-enantiomer has agonist activity at the mGluR8 receptor subtype of metabotropic glutamate
receptors. Thus, combining an AMPA receptor antagonist with a mGluR8 receptor agonist leads to
a potentiation of antiepileptic activity. For further details about glutamate receptors see Chapter 15.
5.4.6 O
NE
E
NANTIOMER
I
S
C
ONVERTED
INTO
THE
O
THER
IN
THE
B
ODY
The interconversion of the enantiomers of thalidomide under physiological conditions has already
been discussed. Another group of drugs, which are known to exhibit this phenomenon, are the
a-arylpropionic acids, which are nonsteroidal anti-inl ammatory drugs (NSAIDs). These drugs are
used to treat rheumatoid arthritis and as analgesics. It is known in the case of naproxen and ibu-
profen (Figure 5.11) that the desired activity resides in the (
S
)-enantiomer while the (
R
)-enantiomer
undergoes metabolic inversion to the (
S
)-enantiomer. Ostensibly, these drugs are safe to give in the
racemic form as the distomer is converted to the eutomer in the body, however, it is known that in
the course of the metabolism of the (
R
)-enantiomer, ibuprofen accumulates in fatty tissue in the
body. The (
S
)-enantiomer is not metabolized in the same fashion and therefore marketing the
biologically active (
S
)-enantiomer could be advantageous.
