9_parkinsons

9_parkinsons - Parkinson's disease (PD) PHAR 301 Drugs and...

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Parkinson's disease (PD) Drugs to know by name PHAR 301 Drugs and Disease - Dr. Paul Clarke • L-DOPA + carbidopa = Sinemet™ romocriptine bromocriptine • selegiline = deprenyl Terms to know ubstantia nigra subs a a g a • striatum = caudate-putamen • nigrostriatal • bradykinesia
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Parkinson's disease (PD) Reading • Brody textbook 5th edition Chapter 28 – omit the sections on Alzheimer's disease – do not memorize Table 28-1 but instead refer to my simplified version
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Aims of this lecture • Symptoms of PD • What use(s) can animal models serve? • Which animal model is "best"? hat causes PD? What causes PD? • Why do we think DA loss is central to PD symptoms? hat are the limitations of L- OPA therapy? What are the limitations of L DOPA therapy? • What is the best treatment currently? • Future treatments? QUESTIONS? [email protected]
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postural problems ill lling tremor rigidity pill-rolling tremor bradykinesia shuffling gait
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80% of PD is idiopathic ain Entry: ·i·o·path·ic Main Entry: id i o path ic Pronunciation: "i-dE-&-'pa-thik arising spontaneously or from an bk obscure or unknown cause
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Early-onset Parkinson's disease (clearly genetic)…. ….very sad BEFORE AFTER
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Environmental factors in PD - revalence of PD in different hydrographic areas Prevalence of PD in different hydrographic areas Barbeau et al 1986
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Prevalence of PD is correlated with pesticide use
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NORMAL PARKINSON'S nigrostriatal pathway dies in PD DA cells
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Nigrostriatal DA neurons die in PD ubstantia triatum nigrostriatal pathway Substantia nigra Striatum Clinical symptoms are not seen until ~70-80% loss of striatal DA occurs But does DA cell loss cause PD symptoms?
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DA pathways in the rat brain - side view Striatum a.k.a. caudate-putamen ront Front Substantia igra Striatum nigra Back
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The nigrostriatal system is needed for reacting to stimuli 6-OHDA administered into the left and right substantia nigra Group Touch Vision Odour Non-lesioned control rats 3.0 ± 0.0 3.0 ± 0.0 3.0 ± 0.0 6-OHDA-lesioned rats 0.6 ± 0.1 0.1 ± 0.1 0.3 ± 0.1 Perfect Impaired 0 = no response 0.0 = no response 3.0 = perfect Marshall and Gotthelf (1979) Experimental Neurology 65: 398-411
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DA enables sensorimotor integration in the striatum SENSORY + Substantia nigra MOTOR
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This note was uploaded on 02/22/2011 for the course PHAR 301 taught by Professor Hales during the Spring '11 term at McGill.

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9_parkinsons - Parkinson's disease (PD) PHAR 301 Drugs and...

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