Download Lecture: Parkinson`s Disease

Salvador Dali (Painter)
Muhammad Ali (Boxer)
Pope John Paul II
Mao Zedong (Chinese Politician) Michael J Fox (Actor)
Janet Reno (Former AG)
The Pharmacology of Parkinson’s
Disease
May 22, 2014
Symptoms of PD
• Resting tremor (“shaking”)- improved with
activity
• Rigidity
• Impaired balance
• Bradykinesia (brady=slow, kinesia=motion)
– Gait disturbances
– Loss of automatic movement (blinking, smiling, etc.)
• Additional symptoms:
– Muscle aches, pains
– Slurred speech
– Cognitive (depression, anxiety, confusion)
PD Age of Onset
Substantia Nigra Changes in PD
Major Circuit Important in PD
Substantia Nigra
Caudate
Just Add Dopamine!
NH3+
But what’s the problem here?
• Not lipid soluble, can’t cross the BBB
What about its precursor- L-DOPA?
NH3+
• L-DOPA is also charged, but it crosses the BBB anyway…
How?
L-DOPA is transported across BBB by
active transport
LAT1 transporter
DDC in the periphery can also
convert L-Dopa to DA-still can’t cross
Current PD Therapy
• Carbidopa + L-Dopa
– Peripheral DOPA decarboxylase (DDC) inhibitor
What could be some other drug targets?
Targets for Another Drug?
DA Receptor Agonists
• Apomorphine
• Ropinirole
MAO Inhibitor
• Selegiline
– Retards degradation of DA
– Somewhat selective inhibitor of an enzyme (MAO)
Can there be a placebo effect in
treating PD?
• How might you answer that question?
STN Firing
Major Points of Today’s Lecture
• PD involves degeneration of the dopaminergic neurons (in the
substantia nigra) that results in tremors, rigidity, and gait
disturbances
• Occurs mostly in the elderly (prevalence increases with age)
• Drugs available to treat PD increase DA synthesis, prevent
metabolism, or activate DA receptors
• The placebo effect is real and produces physiological changes
in patients that can be measured and quantified
Concept Map
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Parkinson’s Disease
Dopamine
Gait disturbances
Substantia nigra
L-DOPA
BBB
DDC
Tremors
Placebo effect