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The Agonist & The Ecstasy: A Primer on PD Medications

by Ken Bernstein

This primer provides a basic explanation of why Parkinson's is a "dopamine deficiency disorder'' and provides explanations about how three categories of Parkinson's medications provide symptomatic relief. The reader should note that in writing a primer on this topic, it was necessary to greatly simplify what is in fact an extremely complex topic.


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What is Parkinson's?

Parkinson's is a neurological disorder that affects voluntary movement. The symptoms are: slowness of movement; rigidity; and tremor. What causes the condition remains unknown, but there is a general consensus that it probably involves the interaction of genetics and environmental toxins. While the cause is still uncertain, much is known about the resulting damage. Parkinson's is progressive and involves the deterioration of very specific areas of the brain that control voluntary movement. There is no known cure yet, but there are a variety of medications that provide symptomatic relief.

How Information Is Transmitted in the Normal Brain

Voluntary movement is a complex task that involves the coordinated processes of several regions [Figure 1] of the brain. Smooth movement can only occur when information freely flows in both directions along the pathways that connect the regions involved in voluntary movement.

Figure 1

The pathways that connect the regions are composed of nerve fibers. An individual nerve cell [Figure 2] is called a neuron.

Figure 2

Among the major parts of a neuron are the cell body, axon, dendrites, and synaptic buttons [Figure 3].

Figure 3

A closer look at the end of one nerve and the beginning of another [Figure 4] will reveal that there is a small space between the synaptic buttons at the end of one neuron and the dendrites that receive messages on a neighboring neuron. This space is called the synaptic gap. A presynaptic neuron is one carrying an impulse toward the gap. A postsynaptic neuron is one which will receive the information coming from the presynaptic neuron.

Figure 4

The transmission of information from one region of the brain to another uses an electrochemical process. Sometimes the information is in the form of a small electrical signal. At other times the information is stored briefly as energy within chemicals which once again release the energy as an electrical signal.

How do electrical signals bridge the synaptic gap? When information in the form of an electrical signal travels down the axon and reaches the synaptic buttons, the signal triggers the release of a special chemical into the synaptic gap. The chemical that carries the information across the synapse is called a neurotransmitter. When the neurotransmitter comes in contact with receptors on the postsynaptic neuron a new electrical signal is produced. This process is repeated until the signal reaches its final intended destination.

How Dopamine is Produced Within a Healthy Neuron

Different regions of the brain use different neurotransmitters. Dopamine is the neurotransmitter used by the regions of the brain that control voluntary movement. In order to understand what happens in Parkinson's, you will need a brief explanation about how dopamine is produced within healthy neurons. The explanation that follows uses the analogy that a neuron is like a chemical plant [Figure 5].

Figure 5

Neurons that produce dopamine are called dopaminergic neurons. A healthy dopaminergic neuron [Figure 6] produces dopamine in a number of steps. The neuron converts tyrosine into L-dopa and then into dopamine. An understanding of this process will prove to be important in understanding how some Parkinson's medications work.

Figure 6

The dopamine that is produced in this process is not always used immediately. Dopamine is stored [Figure 7] within special storage containers called vesicles located within the synaptic buttons.

Figure 7

When an electrical impulse that has traveled down a nerve cell's axon reaches the synaptic button, dopamine stored within some vesicles is released [Figure 8] into the synaptic gap. Some of the dopamine crosses the synaptic gap and locks onto receptors on the receiving nerve cell. This interaction triggers an electrical signal which will continued to be relayed using this electrochemical process until the signal reaches its destination in another region of the brain. The electrical impulse might initiate an activity such as the smooth contraction of a muscle.

Figure 8

Not all of the dopamine released into synaptic gap reaches a receptor. The amount of dopamine floating free is controlled by a number of complex chemical reactions. Some dopamine is recycled, [Figure 9] it is absorbed by the neuron and stored once again within a vesicle. This process is known as re-uptake.

Figure 9

The level of dopamine is also regulated by the chemicals COMT and MAO-B. [Figure 10] These chemicals reduce the level of dopamine in the brain by converting dopamine into other substances.

Figure 10

Now that you have a basic understanding of how a healthy neuron creates and recycles dopamine, we can turn our focus toward the processes involved in Parkinson's.


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