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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 • • • • • • • • • Parkinson’s Disease Dopamine Gait disturbances Substantia nigra L-DOPA BBB DDC Tremors Placebo effect