targets have to be considered. Like the messenger target, these nonmessenger targets
can be divided into three logical groups.
The first category of nonmessenger targets consists of cellular structures that are not
directly influenced by neurotransmitter, hormonal, or immunomodulatory control. A cell
consists of a genetic apparatus (the nucleus), surrounded by biosynthetic machinery (cyto-
plasmic structures such as rough endoplasmic reticulum), encased in a cellular membrane.
This structural arrangement affords a plethora of receptors as targets for drug design. The
outer delineating membrane contains numerous proteins which enable biological infor-
mation to be transmitted from one cell to the next cell (via voltage-gated ion channels) or
from the outside of a cell to the inside of that same cell (via G-protein mechanisms); these
membrane-bound proteins are superb candidate receptors for drug design and have been
successfully exploited in developing drugs for epilepsy, cardiac rhythm problems, and
local anesthetics. Within the cell, the nucleus and its associated nucleic acids offer a rich
assortment of drug targets (DNA replication, transcription, translation, mitosis) that may
be targeted for the treatment of cancer (sarcomas, carcinomas, leukaemia).
The second group consists of the endogenous macromolecules. The most important
of these macromolecules are the enzymes. Enzymes are biological catalysts that
enhance a wide range of biochemical processes. Enzyme inhibitors offer an approach
to therapeutics for a variety of disease processes. More recently, lipids and carbohy-
drates are also being recognized as viable target receptors in drug design.
The final category of nonmessenger targets includes exogenous pathogens such as prions,
viruses, bacteria, fungi, and parasites. These pathogens produce numerous, clinically
common localized infections (e.g., abscesses, meningitis, encephalitis, sinusitis, pneumonia,
gastroenteritis, cystitis), less common infections (e.g., myocarditis, osteomyelitis), and well-
recognized systemic infections (e.g., syphilis, AIDS). Apart from obvious infections caused
by such agents, infections are also implicated in the indirect causation of other pathologies.
For example, bacteria have been implicated as a cause of peptic ulcer disease and may even
play a role in arterial wall damage related to atherosclerosis. Infectious agents have also
been speculated to exert an effect in the etiology of diseases such as multiple sclerosis (for
which attempts to identify a causative virus have been in progress for decades) and even
type 1 diabetes. The most recently appreciated pathogens, prions, have been implicated in
the devastating neurological disorder of Creutzfeldt–Jakob disease and bovine spongiform
encephalopathy (mad cow disease and its human variant). These prion-based neurodegen-
erative diseases produce a rapidly progressive dementia associated with the onset of rapid,
lightning-like seizures (myoclonic seizures) early in the course of the disease.
Drug design that focuses on targets 4–6 is different from drug design around targets 1–3.
For the nonmessenger targets, the presence of a small molecule ligand is less frequent.
Accordingly, it is necessary to find a molecule that influences the nonmessenger receptor
target either via rational drug design (requiring three-dimensional structural knowledge of
the receptor) or via high throughput screening (requiring combinatorial chemistry).
An identification of the pathological process being addressed, combined with an
appreciation of which one of the six biochemical approaches (chapters 4–9) is to be
pursued, enables the task of molecular-level drug design to be undertaken. In designing
the drug to fit the receptor (discussed in detail in chapter 3), the molecular properties that
make a molecule a drug molecule and not just an organic molecule (chapter 1) and the
molecular properties that make a receptor molecule viable as a target (chapter 2) must
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