Parkinsons

Disease Treatment of Motor Symptoms

Brianna Crighton

What is Parkinsons Disease?

A progressive neurological disease that is considered the most
common movement disorder in the world, aecEng about 1%
of adults over the age of 60[4]

The pathology is characterized by the accumulaEon of a
protein called alpha synuclein into inclusions called Lewy
bodies and the insucient formaEon of dopamine, specically
the dopaminergic projecEons from the subtanEa nigra pars
compacta to the striatum[3] The distribuEon of Lewy bodies
varies between individuals and is not conned to the
substanEa nigra[3]

During early stages of the disease the most obvious symptoms
are movement related but behavioral problems may arise later
on as well[3]

EEology is unknown but aging, environmental factors and
geneEc predisposiEon are thought to likely play a role[3]

Treatment

Currently, there is no cure for Parkinsons, but it is possible to live with the disease for
years treaEng the symptoms with medicaEon. Parkinsons can progress at dierent
rates for dierent people, and as symptoms change the medicaEon will need to be
adjusted[1]

No deniEve agent to slow the progression of the disease at the cellular level.
Treatment currently remains symptomaEc with mostly dopaminergic drugs and is
typically iniEated when motor symptoms cause a disability[5]

The most commonly prescribed medicaEons include monoamine oxidase-B (MAO-B)
inhibitors (selegine or resgaline), non-ergot-derived dopamine agonists and
levodopa[3]


Figure 1. Comparison of the substanEa nigra in a
healthy individual to that in Parkinsons Disease.
Retrieved on March 12, 2015 from hlp://
pt851.wikidot.com/parkinsons-disease-cell-biology

Figure 5. PET scan image to highlight two examples of the amount of dopamine acEvity in the striatum (red) of a normal person and a Parkinsons
paEent pre and post treatment. Retrieved on March 12, 2015 from hlp://www.parkinson.org/PaEents/PaEents---On-The-Blog/April-2014/An-
Update-on-DAT-Scanning-for-Parkinsons-Disease

Motor Symptoms

The main motor symptoms are collecEvely

called Parkinsonism

Four cardinal features include:
- Tremors
- Slowness and SEness
- Postural Instability
- Rigidity
These classical motor features begin to
develop when about 50% of dopaminergic
nigrostriatal neurons and about 80%
striatal dopamine producEon are lost[5]

MAO-B Inhibitors
Treatment with an MAO-B inhibitor combined with a dopamine agonist may
control motor symptoms for the rst 25 years, but the likelihood of requiring
levodopa afer that increases signicantly[3]

How it works:
- It prevents the breakdown of dopamine in the brain by inhibiEng the enzyme
monoamine oxidase type B[1]
- It is ofen used to make the eects of levodopa last longer or to reduce the
amount required[1]

Side Eects:
- Selegine can cause confusion, hallucinaEons, postural dizziness, insomnia and
dyskinesias when taken with levodopa, because of the increased dopamine[2]
- Resgaline has been shown to have fewer side eects with levodopa[2]

Figure 2. Dopamine loss at the synapEc level in Parkinsons.

Retrieved on March 12, 2015 from hlp://blogs.brandeis.edu/yonthewall/
translaEonal-ndings-how-fruit-ies-are-helping-us-understand-parkinsons-
disease/

Dopamine Agonists
Figure 4. Dopamine Metabolism and the acEon of levodopa, monoamine oxidase inhibitor type B inhibitors, and dopamine agonists. AbbreviaEons:
VMAT2, Vesicular monoamine transporter 2; DAT, dopamine acEve transporter; DOPAC, 3,4-dihydroxyphenylaceEc acid; 3MT, 3-methoxytyramine; HVA,
homovanillic acid (Teo & Ho, 2013).

Levodopa

Figure 3. Brain Regions Aected by Parkinsons Disease. Retrieved on March 12, 2015 from hlp://www.calgarycmmc.com/parkinsonsdisease.htm

References
1. Heisters, D. (2011). Parkinsons: Symptoms, treatments and research. Bri$sh Journal of Nursing, 20(9), 548-554.
2. Lindahl, A., & MacMahon, D. (2011). Parkinsons: TreaEng the symptoms. Bri$sh Journal of Nursing, 20(14), 852-857.
3. Samii, A. (2009). Parkinson disease. In M.D Binder, N Hirokawa & U Windhorst (Ed.), Encyclopedia of Neuroscience (Vol. 1, pp. 3089-3091). Berlin: Springer.
4. Samii, A., Nul, J., & Ransom, B. (2004). Parkinson's disease. The Lancet, 363, 1783-1793.
5. Teo, K., & Ho, S. (2013). Monoamine oxidase-B (MAO-B) inhibitors: ImplicaEons for disease-modicaEon in Parkinsons disease. Transla$onal Neurodegenera$on, 2(19),
153-163.
6. The Parkinson's Group. (2000). Pramipexole vs Levodopa as IniEal Treatment for Parkinson Disease. The Journal of the American Medical Associa$on, 384, 1931-1938.
7. The Parkinson's Group. (2004). Levodopa and the progression of parkinsons disease. The New England Journal of Medicine, 351, 2498-2508.

Levodopa is currently the most eecEve medicaEon used for treaEng motor
symptoms.

How it Works:
- It is a chemical building block is converted into dopamine in the body, replacing
the dopamine lost from neurons[1]
- This increases the level of dopamine that reaches the brain and sEmulates the
areas of the brain where dopamine works[1]
- It can be used at the stages of the condiEons[1]

Side Eects:
- Early levodopa exposure is thought to adversely aect the course of the
disease, potenEally leading to dopaminergic complicaEons[6]
- However, evidence is controversial and it has consistently shown to eecEvely
slow the progression of symptoms[7]

Agonists at dopamine receptor sites have been proposed as alternaEve early

treatment to levodopa[6]

How it works:
- It mimics the eect of dopamine without having to be converted. It sEmulates
dopamine receptors and can prevent side eects like involuntary movements[1]
- Apomorphoine is administered subcutaneously and is the strongest known
dopamine agonist[1]
- Ergot-Derived dopamine agonists are older drugs that are rarely used now
because of potenEally dangerous side eects, requiring regular blood monitoring[2]

Side Eects:
- Problems controlling impulsive or compulsive behavior but dyskinesia is not
common[2]

Conclusion
Treatment largely depends progression of the disease and on the individual.
Levodopa is one of the most commonly used medical treatment opEons but there
is controversy surrounding the possibility of it adversely aecEng the course of the
disease over prolonged usage. For this reason, other treatment opEons have been
used iniEally and/or in conjuncEon with levodopa.