Chemistry Reference
In-Depth Information
to pick up another molecule to transport. A drug that is similar in structure
to an essential natural compound can, in some cases, fool the transport
mechanism and be absorbed actively into the body. The anticancer drug
melphalan
was synthesised in order to make use of the existing active trans-
port pathway for the amino acid phenylalanine (see Figure 2.7). The phenyl-
alanine part of the molecule takes no part in the anticancer action; it is
merely there to improve the molecule's chances of being absorbed across
biomembranes. Interestingly, only the natural
L
-phenylalanine analogue of
melphalan is absorbed actively; the opposite
D
form is only absorbed slowly
by passive diffusion. This fact neatly illustrates that active transport, like
most of the body's biochemical mechanisms, is chiral in nature, and can
easily discriminate between enantiomers.
Cl
N
H
NH
2
O
Melphalan
Cl
C
OH
H
NH
2
O
Phenylalanine
C
OH
Figure 2.7
The structures of melphalan and phenylalanine.
The action of local anaesthetics
The physicochemical properties of drugs that underlie their absorption
within the body can be complex, and the pH partition hypothesis is not
sufficiently comprehensive to explain all the processes that occur
in vivo
; it
is, however, a good place to start. Perhaps surprisingly for such a simple
theory, the pH partition hypothesis can explain quite complicated pharma-
cological observations. The processes that occur when a patient swallows a
tablet are so complicated that the most powerful computers known to
science cannot adequately model the process. It is astonishing, therefore,
that a few physicochemical constants (p
K
a
and partition coefficient, for
example) can provide useful information and, when used properly, predict
