Medicinal Chemistry

systems (cardiac, respiratory, gastrointestinal, genitourinary) and structural systems
(musculosketelal, dermatological). The control systems can exert immense control over the
support systems: the nervous system, through its autonomic division, can influence heart
rate, the diameter of blood vessels, respiratory rate, the diameter of bronchioles within
the lung, gastrointestinal motility and secretions, and bladder contractility. Drug design
expertise obtained within one of these systems frequently extends from one disease to
another within that same, single physiological system. For example, in drug design for
the nervous system, designing drugs to cross the blood–brain barrier is useful for many
diseases of the brain. Also, a system-centered approach enables a single receptor to be
evaluated in many disease states. If drugs are being developed as antiglutamatergic
NMDA antagonists, their potential utility in a range of medical problems including
epilepsy, stroke, or psychiatric disorders, can be evaluated.

2.11.3 Pathological Process-Centered Receptor Selection

Finally, the drug designer could pursue a pathological process-centered (e.g., vascular
atherosclerosis, neoplasia, inflammation, infection, apoptosis) approach. Drugs
designed to target one of these pathological processes may be used against different dis-
eases in different physiological systems. For example, drugs designed to treat infections
may be used for infections extending from a sinusitis in the facial region to an abscess
of the foot; likewise, a drug designed to treat neoplasia may be used for cancers in the
lungs, bowel, or liver. Drugs developed for vascular disorders can be used to treat med-
ical problems as diverse as myocardial infarction (heart attack), cerebral infarction
(stroke), intermittent claudication (leg pain while walking, due to decreased blood
supply), or erectile dysfunction. Finally, drugs that target apoptosis (i.e., suppressing
genetically encoded, preprogrammed cell death) could in theory be employed against a
wide variety of degenerative and neurodegenerative disease states.

2.11.4 Molecular Process-Centered Receptor Selection

The above-mentioned three time-honored approaches to receptor site selection are
based upon a conceptualization of human disease at either a gross anatomical or
histopathological degree of structural refinement. The pharmacist or drug designer,
however, must always exploit atomic- and molecular-level thinking organized within a
biochemical framework. Drugs are therapeutic molecules that alter the biochemistry of
the human state; accordingly, they must be designed at a molecular level. To enable this
biochemical conceptualization of drug action, this book identifies six drug design tar-
gets that facilitate therapeutic molecule design and drug receptor selection at an atomic
and molecular level of structural refinement (reflected in Part II):

1. Messenger targets: drugs that target neurotransmitters and their receptors (chapter 4)


2. Messenger targets: drugs that target hormones and their receptors (chapter 5)


3. Messenger targets: drugs that target immunomodulators and their receptors (chapter 6)


4. Nonmessenger targets: drugs that target endogenous cellular structures (chapter 7)


5. Nonmessenger targets: drugs that target endogenous macromolecules (chapter 8)


6. Nonmessenger targets: drugs that target exogenous structures (chapter 9)

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