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Salvador Dali (Painter)
Mao Zedong (Chinese Politician) Michael J Fox (Actor)
Pope John Paul II
Muhammad Ali (Boxer)
Janet Reno (Former AG)
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The Pharmacology of Parkinson’s Disease
May 22, 2014
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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)
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PD Age of Onset
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Substantia Nigra Changes in PD
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Major Circuit Important in PD
Substantia NigraCaudate
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Just Add Dopamine!
But what’s the problem here?
• Not lipid soluble, can’t cross the BBB
NH3+
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What about its precursor- L-DOPA?
• L-DOPA is also charged, but it crosses the BBB anyway… How?
NH3+
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LAT1 transporter
L-DOPA is transported across BBB by active transport
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DDC in the periphery can also convert L-Dopa to DA-still can’t cross
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Current PD Therapy• Carbidopa + L-Dopa
– Peripheral DOPA decarboxylase (DDC) inhibitor
What could be some other drug targets?
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Targets for Another Drug?
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DA Receptor Agonists
• Apomorphine • Ropinirole
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MAO Inhibitor
• Selegiline
– Retards degradation of DA– Somewhat selective inhibitor of an enzyme (MAO)
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Can there be a placebo effect in treating PD?
• How might you answer that question?
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STN Firing
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• 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
Major Points of Today’s Lecture
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Concept Map
• Parkinson’s Disease• Dopamine• Gait disturbances• Substantia nigra• L-DOPA• BBB• DDC• Tremors• Placebo effect