Chemistry Reference
In-Depth Information
The glucuronide derivatives formed in this way are much more water
soluble than the parent drug. This is due to the large number of polar OH
groups and a carboxylate group that will ionise at neutral pH. The
glucuronide derivatives are less active pharmacologically and more easily
excreted than the drug itself. Glucuronic acid conjugation is therefore,
for most drugs, an example of a process that terminates drug action. An
important exception to this is the analgesic morphine. This important drug
forms a 3-
O
- and a 6-
O
-glucuronide, both of which are active at opiate
receptors in the body (see Figure 5.2). The overall analgesic effect of
morphine is a combination of the action of the drug and the effects of both
active glucuronides and is, as a result, very complex.
2
COO
-
HO
3
1
O
O
4
OH
11
10
12
O
HO
13
9
OH
H
5
6
14
N
HO
H
8
7
3-
O
-glucuronide
CH
3
H
Morphine
COO
-
O
OH
O
HO
H
OH
Figure 5.2
The structures of morphine and its 3-O- and 6-O-glucuronides.
Sulfate conjugation
Drugs and hormones that contain the phenolic functional group are
metabolised by conjugation to a sulfate group (a process called sulfation).
Examples of compounds metabolised in this way include the neuro-
transmitter noradrenaline (norepinephrine) as well as hormones such as
