C H A P T E R 2 4
Antiparkinsonism agents
373
I
n the 1990s, several prominent figures—including
former heavyweight boxing champion Muhammad
Ali and actor Michael J. Fox—revealed that they had
Parkinson’s disease
, a progressive, chronic neurological
disorder. In general, Parkinson’s disease may develop
in people of any age, but it usually affects those who
are past middle age and entering their 60s or even later
years. Therefore, the occurrence of Parkinson’s disease
in these well-known individuals who were relatively
young at the time of diagnosis is that much more inter-
esting. The cause of the condition is not known.
At this time, there is no cure for Parkinson’s disease.
Therapy is aimed at management of signs and symptoms
to provide optimal functioning for as long as possible.
PARKINSON’S DISEASE AND
PARKINSONISM
Lack of coordination is characteristic of Parkinson’s
disease. Rhythmic tremors develop, insidiously at first.
In some muscle groups, these tremors lead to rigidity,
and in others weakness. Affected people may have
trouble maintaining position or posture, and they may
develop the condition known as
bradykinesia
, marked
by difficulties in performing intentional movements and
extreme slowness or sluggishness.
As Parkinson’s disease progresses, walking becomes
a problem; a shuffling gait is a hallmark of the condition.
In addition, people may drool, and their speech may be
slow and slurred. As the cranial nerves are affected, they
may develop a mask-like expression. Parkinson’s disease
does not affect the higher levels of the cerebral cortex,
so a very alert and intelligent person may be trapped in a
progressively degenerating body.
Parkinsonism
is a term used to describe the Parkin
son’s disease–like extrapyramidal symptoms that are
adverse effects associated with particular drugs or
brain injuries. People typically exhibit tremors and
bradykinesia.
Pathophysiology
Although the cause of Parkinson’s disease is not known,
it is known that the signs and symptoms of the disease
relate to damaged neurons in the basal ganglia of the
brain. Theories about the cause of the degeneration of
these neurons range from viral infection, blows to the
head, brain infection, atherosclerosis and exposure to
certain drugs and environmental factors.
Even though the actual cause is not known, the
mechanism that causes the signs and symptoms of
Parkinson’s disease is understood. In a part of the brain
called the
substantia nigra
, a dopamine-rich area, nerve
cell bodies begin to degenerate. This process results in a
reduction of the number of impulses sent to the
corpus
striatum
in the basal ganglia. This area of the brain, in
conjunction with the substantia nigra, helps to maintain
muscle tone not related to any particular movement. The
corpus striatum is connected to the substantia nigra by
a series of neurons that use gamma-aminobutyric acid
(GABA), an inhibitory neurotransmitter. The substantia
nigra sends nerve impulses back into the corpus stratum
using the inhibitory neurotransmitter dopamine. The
two areas then mutually inhibit activity in a balanced
manner.
Higher neurons originating in the cerebral cortex
secrete acetylcholine (an excitatory neurotransmitter) in
the area of the corpus striatum to coordinate intentional
movements of the body. When dopamine decreases in
the area, a chemical imbalance occurs that allows the
cholinergic or excitatory cells to dominate. This affects
the functioning of the basal ganglia and the cortical
and cerebellar components of the extrapyramidal motor
system. The extrapyramidal system is one that provides
coordination for unconscious muscle movements,
including those that control position, posture and
movement. The result of this imbalance in the motor
system is apparent as the manifestations of Parkinson’s
disease (Figure 24.1).
Basal ganglia
Degeneration of dopamine-releasing
neurons leads to Parkinson’s disease
Dopamine
ACh
+++
Corpus striatum
Substantia nigra
–
–
–
–
–
–
–
GABA
FIGURE 24.1
Schematic representation of the
degeneration of neurons that leads to Parkinson’s
disease. Cells in the corpus striatum send impulses
to the substantia nigra using gamma-aminobutyric
acid (GABA) to inhibit activity. In turn, the
substantia nigra sends impulses to the corpus
striatum, using dopamine, to inhibit activity.
Cortical areas use acetylcholine (ACh) to stimulate
intentional movements.
