contains 150 mL of CSF, with a CSF secretion rate of 0.4 mL/min; thus, the total CSF
in the brain is completely replaced 3–4 times per day. CSF is a dilute aqueous solution
of Na+and Cl−. CSF fulfills a number of functions, including protecting the brain from
trauma by its buoyancy, functioning as a “sink” to remove certain substances from the
brain, and influencing message transduction by facilitating hormonal and molecular
transport within the brain. The central cavity system, which contains the CSF, is com-
posed of the central canal(in the spinal cord), the fourth ventricle(between the pons
and the cerebellum), the third ventricle(within the diencephalon), and the lateral ven-
tricles(within the cerebral hemispheres). This fluid-filled pathway may be used to
administer drugs directly (albeit with a limited distribution) into the CNS via intrathe-
caladministration by delivery into the thecal sac that lies outside of the spinal cord.
When there is an excess of CSF, the condition is referred to as hydrocephalus. Although
frequently treated surgically, hydrocephalus may also be treated with enzyme inhibitors
such as carbonicanhydrase enzyme inhibitors (e.g., acetazolamide); this observation is
of interest to the medicinal chemist working on diuretics and the carbonic anhydrase
system.
Since the brain is so extremely active in the electrical control of short-term home-
ostasis within the body, it is an ideal target for drug design. However, this high degree of
activity also gives the brain a voracious appetite for glucose and oxygen as provided by
the bloodstream. Indeed, the brain has the highest consumption of blood of any organ
system in the body. As a generalization, blood supply to the back of the brain (brainstem,
cerebellum, occipital cortex) is from the vertebrobasilar (VB) artery and the associated
posterior cerebral artery (PCA); blood supply to the front of the brain (frontal and pari-
etal cortex) is from the internal carotid (IC) and its anterior cerebral artery (ACA) and
middle cerebral artery (MCA) branches. Either blockage (via atherosclerosis) or rupture
(secondary to arterial hypertension) of any of these arteries will lead to a stroke, which
in turn triggers a cascade of neurotransmitter events which may (or may not be)
amenable to molecular manipulation by the medicinal chemist (section 4.9.3).
The other part of the central nervous system is the spinal cord. As a reversal of the
trend in the brain, the spinal cord has white matter on the outside and gray matter on
the inside. The spinal cord is divided into several divisions: cervical, thoracic, lumbar,
and sacral. It lies protected in the bony spinal column constructed from individual ver-
tebral bodies. Damage to the spinal cord is common and leads to severe disabilities (i.e.,
diplegia [paralysis of both legs] or quadriplegia [paralysis of all four extremities]—to
be distinguished from hemiplegia [paralysis of one leg and arm on the same body side]
which is a symptom of brain injury or damage). Currently, there are virtually no drugs
available for spinal cord problems. Glycine receptors, especially those in the cervical
region of the spinal cord, may have some utility in the development of therapies for the
treatment of muscle spasticity following CNS injury (section 4.8). The spinal cord is
extremely important because it is a conduit for all ascending information traveling up
to the brain and descending information traveling down from the brain.
Commands from the CNS to the organs of the body (e.g., heart, lungs, bowel, blad-
der) are conveyed by the autonomic nervous system, whereas commands to the skeletal
muscles are transmitted by the sensorimotor system. Likewise, information from the
heart, lungs, and other viscera are conveyed back to the CNS via the autonomic nervous
system and information from the skin (i.e., pain, pressure, touch) is sent to the CNS via
202 MEDICINAL CHEMISTRY