8.6 Carbohydrates as Drugs and Drug Design Targets
Carbohydrates are underexploited as receptors against which to target drugs and under-
utilized as leads in drug discovery. The role of carbohydrates has regrettably been gen-
eralized to functioning primarily as energy stores. The functional and structural role of
carbohydrates has been somewhat neglected. Moreover, the capacity of carbohydrates
to provide large numbers of molecules with diversity and complexity has not been fully
explored. For example, when two identical amino acids or nucleotides are connected,
they can produce just one dipeptide or dinucleotide; but when two identical saccharides
are joined, 11 different disaccharides are possible. In modern medicinal chemistry, the
ability to generate families with molecular diversity is an asset; carbohydrates possess
such ability.
Over the years, few carbohydrates have emerged as drug candidates or drug additives.
Of the sugar alcohols, sorbitol (8.84) produces sweet and viscous solutions that are used
in the formulation of pharmaceutical preparations such as cough syrups. Mannitol (8.85),
on the other hand, is used as an actual drug. Since mannitol creates an osmotic gradient
within the proximal tubules, distal tubules, and collecting ducts of the kidney, it functions
as a potent diuretic. This strong diuretic property has resulted in mannitol being used to
treatincreased intracranial pressure. The volume of the human skull is fixed; the bones
of the skull are not expandable. When a brain hemorrhage or some other brain pathology
uses volume within the skull, the contents of the skull become more crowded, producing
increased pressure within the cranium. A diuretic, such as mannitol, dehydrates the brain
temporarily, making more room within the skull and decreasing intracranial pressure.
Starch, a high-molecular-weight carbohydrate composed of amylose (20%) and amy-
lopectin(80%), is used as an excipient additive in drug tablet formulation. Ferrous
gluconate (8.86) is a carbohydrate salt of iron that is used (for its iron content, rather
than its carbohydrate content) to treat iron deficiency anemia.
The single most important drug molecule based on a carbohydrate structure is heparin.
Heparin is a heterogeneous mixture of sulfated mucopolysaccharides; it is composed of
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