Parkinson

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Parkinsons Disease and Treatment

• Shalla Hanson
• Medicinal Chemistry April 2009

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Description of Disease

• Parkinsons disease (PD) is typically considered
  a chronic, progressive neurodegenerative movement
  disorder. However, it is now known to have
  variety of nonmotor symptoms as well.

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Major Symptoms-TRAP

• Tremor
• Rigidity
• Akinesia/Bradykinesia
• Postural Instability
• Other motor symptoms include
• Gait
• Dystonia
• Hypophonia
• Drooling
• Dysphagia
• Fatigue
• Akathesia

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Nonmotor Symptoms

• Mood20-80 suffer from depression.
• Behaviorindirectly, e.g., a result of dementia,
  depression.
• Thinking-slowed reaction time and executive
  dysfunction
• Sensationimpaired sense of smell
• Excessive daytime sleep, insomnia, and REM sleep
  disturbances.
• Vision problems
• Impaired proprioception
• Oily skin
• Weight loss
• Incontinence
• Constipation
• Drooling

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Primary Known Causes

• Idiopathicmajority of cases
• Genetic
• Drug inducedCalcium Channel Blockers
• ToxinsSupported by the geographically varied
  incidence
• Head Trauma
• Cerebral Anoxia

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Pathophysiology

• Decreased stimulation of the motor cortex by the
  basal ganglia, usually due to the inadequate
  production and action of dopamine (produced in
  the dopaminergic neurons of the brain.)
• The specific region affected seems to be the
  pars compacta in the substantia nigra where there
  is a marked loss in dopaminergic cells.
• We also see a considerably high activity in the
  cells of the Subthalamic nucleus, which inhibits
  movement.
• High presence of Lewy bodies in dopaminergic
  cells.

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Diagnosis

• PET Scandecreased dopaminergic activity in the
  substantia nigra
• Unified Parkinsons Disease Rating Scalecognitive
  interview
• Normal CT
• Normal MRI

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History

• PD was first described in detail by James
  Parkinson in 1817 in An Essay on the Shaking
  Palsey.
• Carlsson in 1950, determined that dopamine was a
  neurotransmitter and was exceptionally
  concentrated in the basal ganglia.
• Carlssons research later showed that Reserpine
  demonstrates a correlation between motor
  impairment and decreased dopamine levels. L-Dopa
  also given to animals which alleviated symptoms
  and initiated medicinal therapies for PD in 1967.
  
• In California in 1980 a group of opiate addicts
  consumed MPTP N-methyl-4-phenyl-1,2,3,6-tetrahydro
  pyridine, and revealed a pro-toxin, allowing
  another animal model of PD.

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Treatment

• Education
• Exercise
• Nutrition
• Psychiatric counseling

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Treatment

• Oral Medication
• L-Dopa (aka Levodopa)
• Most popular treatment
• Form of dopamine which is able to cross the BBB
  through transport in L-AA system and can then be
  metabolized to dopamine.
• Sinemet levodopa carbidopa

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Treatment

• Oral Medications
• MAO-B Inhibitors
• Selegiline most common
• Dopamine Agonists
• Ropinirole
• Apomorphine
• Lisuride
• COMT Inhibitors (Catachol-O-methyl transferase
  Inh.)
• Tolcapone
• Entacapone
• Stalevo levodopa, carbadopa, and entacapone

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Treatment

• Surgical Procedures
• Deep Brain Stimulation
• Creating a lesion in the subthalamic nucleus or
  globus pallidus

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Current Research

• Gene Therapy
• GAD Glutamic Acid Decarboxylase
• Deep Brain Stimulation
• Controlled Impulses
• Pallidotomy-not enough data to assess results
  well
• Subthalotomyimprovements in contralateral
  rigidity
• Subthalamic Deep Brain Stimulationmimics
  Levodopa

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Works Cited

• Britton, Thomas C. "NONMOTOR ASPECTS OF
  PARKINSON'S DISEASE." Current Medical Literature
  Neurology 20 (2004) 45-50.
• "Parkinson's Disease." Current Medical
  Literature Neurology 23 (2007) 44-48.
• Marceglia, Sara, and Alberto Priori. "Sex, genes,
  hormones and nigral neurodegeneration two
  different Parkinson's diseases in males and in
  females." Future Neurology 2 (2007) 499-503.
• "Literature Review Pathophysiology." Current
  Medical Literature Parkinson's Disease 5 (2003)
  59-61.
• "Literature Review Medical Treatment." Current
  Medical Literature Parkinson's Disease 5 (2003)
  66-70.
• "Literature Review Surgical Treatment." Current
  Medical Literature Parkinson's Disease 5 (2003)
  71-72.

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