synthesis and in vitro pharmacology of a series of histamine h2 ...

Chapter 2
1 prodrugs
2 twin drugs a) identical twins
3 pseudo-hybrids
4 hybrid drugs
b) non-identical twins
Scheme 1: Classification of hybrid molecules
2.1 Prodrugs
c) symmetrical drugs ("siamese twins")
Prodrugs are used to increase the bioavailability and/or the local concentration of
drugs. These prodrugs contain a chemical moiety which, after administration, is
cleaved from the parent drug. This implies that the metabolite of the applied
compound contains the pharmacological activity, while the prodrug itself is often
inactive. Depending on the target area of action and the physicological properties of
the drug, lipophilic or hydrophilic structural moieties are used. L-DOPA is an example
of a naturally occurring (endogenous) prodrug which is metabolized by the enzyme
DOPA-decarboxylase into dopamine. Prednisolone succinate (fig. 1) is an example of
a synthetic prodrug. The succinate moiety adds hydrophilicity to the steroid
derivative and is split after administration.
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Figure 1: The prodrugs 1-DOPA and prednisolone
2.2 Twin drugs
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Compounds classified as twin drugs are not hybrid molecules in the definition of our
classification. Although the non-identical twin drugs exist of two structural different
moieties, these compounds are considered as chemical hybrids and not as
pharmacological hybrids.
All twin drugs are in vivo metabolized into their parent drugs. Actually, also twin
drugs can be considered as prodrugs from which the original drug molecules are
released. A schematic representation of twin drugs and their metabolites is given in
figure 2.
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