therefore, it is of interest to the design of agents for appetite control. The pituitary gland
is attached to the hypothalamus and is crucial to the synthesis of many neurohormonal
messenger molecules (chapter 5). The pineal glandis part of the epithalamus and is
important to the timing of the onset of puberty. The pineal gland contains melatonin,
biosynthetically derived from serotonin (section 4.5.1).
Running up the centre of the brainstem is a region called the reticular activating
system. This region is influenced by a diversity of neurotransmitters (e.g., serotonin,
norepinephrine, GABA) and is central to human consciousness and sleep, being
involved in pharmacologically induced sleep. The raphe nuclei are in the middle of the
brainstem (in the midline of the medulla, pons, and mesencephalon); they are associ-
ated with the reticular formation and are actively involved with the biosynthesis of sero-
tonin (section 4.5.1). The brainstem (particularly the medulla and pons) is crucial to
life, with many injuries to the brainstem being rapidly lethal; the drug designer who
targets receptors in the brainstem must keep in mind a deep appreciation for the funda-
mental role of the brainstem in life.
The cerebrum is made up of gray matterstructures and white matterstructures. Gray
matter is composed of neuronal cell bodies (i.e., soma); white matter is composed of
nerve fibres (e.g., axons) coated in fatty insulation called myelin. The cerebrum is com-
posed of two gray matter areas: an inner region called the basal ganglia(located adja-
cent to the diencephalon at the top of the brainstem) and an outer region called the
cerebral cortexthat lines the outer surface of the brain. Between these two gray matter
regions lies an extensive zone of white matter. This zone contains the insulated wiring
that carries information from the body to the brain via ascending vertical tracts, from
the brain to the body via descending vertical tracts, and from one part of the brain to
another part of the brain via horizontal tracts. Since multiple sclerosis (MS) is exclu-
sively a disease of white matter (in which discrete regions of white matter become
“demyelinated,” giving rise to short circuiting within the brain’s electrical network),
this area is of importance to drug design for demyelinating diseases; interferons
(chapter 6) are now used in the treatment of MS.
The innermost gray matter region of the cerebrum is the basal ganglia region. The
basal ganglia consists of three major components:caudate nucleus,putamen, and
globus pallidus. Collectively, the caudate nucleus and putamen are referred to as the
striatum; collectively, the putamen and globus pallidus are referred to as the lenticular
nucleus. The basal ganglia are heavily involved in motor activity. The term extrapyra-
midal systemis used clinically to denote components of the basal ganglia that influ-
ence motor activity. Motor activity is intricately controlled by the interaction of three
major systems: the cerebral cortex (controlling voluntary movements via the pyrami-
dal systemand causing spasticity and loss of volitional movement when injured), the
basal ganglia (modulating static postural activities via the extrapyramidal system and
causing rigidity, involuntary movements, and tremor when injured) and the cerebellum
(facilitating coordination of movements and causing ataxia [staggering] when injured).
Because of its central role in movement, the basal ganglia is an area in which many
neurotransmitters deliver either excitatory (+) or inhibitory (−) messages (e.g.,
dopamine (−), acetylcholine (+), glutamate (+),γ-aminobutyric acid [GABA] (−), and
substance P (+)). By manipulating these neurotransmitters, the medicinal chemist can
aid in the treatment of a number of diseases, including Parkinson’s disease (targeting
200 MEDICINAL CHEMISTRY