The neuron is the fundamental structural unit of the nervous system. Each neuron is
also a functioning “bioelectric unit”, capable of generating and transmitting electrical
information (sections 4.1.2 and 4.1.3). When a neuron is damaged by some pathologi-
cal process (e.g., trauma, infection), it may neurochemically respond in one of two
ways: either the neuron can quit functioning (leading to negative—loss of function—
symptoms, such as the limb paralysis associated with stroke; section 4.9.3) or it can
hyperfunction (leading to positive—excessive function—symptoms, such as the limb
shaking associated with epilepsy).
Neurons are not the only cells contained within the central nervous system. The ner-
vous system is also rich in glial cells, which function as support cells. Glial cells are
biosynthetically active cells possessing protein-laden membranes that offer a wealth of
potential “druggable targets” for the medicinal chemist. There are four types of glial cells:
astrocytes,oligodendrocytes,microglialcells and ependymalcells. Astrocytes are work-
horse cells. Most importantly, they are neurochemically active and involved in the
exchange of metabolites between neurons and the blood and also in the uptake of neuro-
transmitter molecules from the synaptic cleft. Astrocytes are also an essential structural
component of the blood–brain barrier (chapter 3), the most important pharmacokinetic
hurdle to drug design for the central nervous system. Oligodendrocytes are responsible for
producing and maintaining the myelin sheaths (fatty insulation layer) surrounding neu-
ronal axons in the central nervous system. Not surprisingly, oligodendrocytes may play a
role in multiple sclerosis (chapter 6). Microglia function as neural macrophages, respon-
sible for phagocytosis (a defense mechanism which involves ingesting and removing par-
ticles or substances foreign to the brain; from the Greek,phagein, to eat). Ependymal cells
line the fluid-filled cavities within the brain.
In addition to providing druggable targets for the drug designer, glial cells are also
important in medicinal chemistry because they are the primary source of brain tumors.
The majority of brain tumors arise from glial cells, not neurons. This is not surprising,
given the observation that glial cells are much more active in cellular division than neu-
rons; brain cells, unlike other cells (e.g., liver cells) do not tend to proliferate after
injury. Gliomasare common brain tumors. Astrocytes are a frequent source of brain
tumor, giving rise to astrocytomasand the extremely deadly glioblastoma multiforme.
The development of anticancer agents for brain tumors is a technically challenging
activity within medicinal chemistry.
4.1.2 Nerve ConductionNerve conduction is the process whereby electrical information is passed along the
length of a given brain cell. As a process, nerve conduction is vulnerable to (and use-
ful for) a properly designed drug. All cells show transmembrane electric potential.
A microelectrode placed into a cell will indicate a potential that is 50–80 mV more
negative than the potential recorded by an electrode outside the cell. This condition is
a result of ion imbalance. Inside the cell, there is a high K+ion concentration (about
120 mM) and low Na+concentration (about 20 mM); the reverse is true outside the
cell. In addition, there is a negative charge inside the cell because the protein anions of
the cytosol are not counterbalanced by cations. The buildup of this negative charge
NEUROTRANSMITTERS AND THEIR RECEPTORS 195