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Parkinson Disease And Other Neurodegenerative Disorders


Parkinsons Disease

Parkinsonism has four cardinal features:

  1. Bradykinesia (slowness and poverty of movement),
  2. Muscular rigidity,
  3. Resting tremor (which usually abates during voluntary movement),
  4. Impairment of postural balance leading to disturbances of Gait and falling.

*The pathological hallmark of PD is a loss of the pigmented, dopaminergic neurons of the substantia nigra pars compacta (SNpc) that provide dopaminergic innervation to the striatum (caudate and putamen).


Management of the Nonmotor and Nondopaminergic Features of Parkinsons Disease


  1. Depression: Approximately 50% of PD patients suffer depression during the course of the disease. SSRI with MAO inhibitors should be given to treat these symptoms.
  2. Psychosis:  Psychosis can be a major problem in PD. Clozapine is the most effective, but it can be associated with agranulocytosis.
  3. Dementia: Dementia in PD is common, affecting as many as 80% of patients.
  4. Levodopa and other dopaminergic drugs can aggravate cognitive dysfunction.
    1. Drugs are usually discontinued in the following sequence: anticholinergics, amantadine, dopamine agonists, COMT inhibitors, and MAO-B inhibitors.
    2. Anticholinesterase agents such as rivastigmine and donepezil reduce the rate of deterioration of measures of cognitive function in controlled studies and can improve attention.
    3. Memantine, an antiglutamatergic agent, may also provide benefit for some PD patients.


  • Majority of the cases are idiopathic, stroke, some are arteriosclerotic whIle postencephalitic are now rare. Wilson's Disease (hepatolenticular degeneration) due to chronic copper poisoning, is a rare cause. Drugs in common clinical use that may cause Parkinsonism include antipsychotics such as haloperidol and thiorid azine and antiemetics such as prochloperazine and metoclopramide.

Dopamine is broken down into inactive metabolites by a set of enzymes, monoamine oxidase (MAO), aldehyde dehydrogenase (ALDH), and catechol-O-methyl transferase (COMT), acting in sequence.



Drugs affecting brain Dopaminergic system

Drugs affecting brain Cholinergic system

(a) Dopamine precursor: Levodopa (L-dopa)

(b) Peripheral decarboxylase inhibitors: Carbidopa, Benserazide.

(c) Dopaminergic agonists: Bromocriptine, Ropinirole, Pramipexole etc (see below)

(d) MAO-B inhibitor: Selegiline, Rasagiline

(e) COMT inhibitors: Entacapone, Tolcapone

(f) Dopamine facilitator: Amantadine.

(a) Central anticholinegics: Trihexyphenidyl (Benzhexol), Procyclidine, Biperiden, Benzatropine

(b) Antihistaminics : Orphenadrine, Promethazine.




  • Dopamine agonists (DA)


D 2

D 3













Symptoms of Parkinson’s disease

a. Rigidity        
b. Tremors (MC)                  
c. Bradykinesia              
d. Festinating Gait


Surgical Procedures For PD

High-frequency deep brain stimulation

Thalamotomy (for conspicuous tremor) or posteroventral pallidotomy.


Gene Therapy In Pd (In Phase 1 Trial):

Infusion into the striatum of Adeno-associated virus type 2 as the vector for the gene:

  • The genes were for glutamic acid decarboxylase (GAD) to facilitate synthesis of GABA, an inhibitory neurotransmitter), infused into the subthalamic nucleus to cause inhibition;
  • For aromatic acid decarboxylase (AADC), infused into the putamen to increase metabolism of levodopa to dopamine; and
  • For neurturin (a growth factor that may enhance the survival of dopaminergic neurons), infused into the putamen.


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