Parkinson's disease is a neurodegenerative disorder caused by the loss of dopamine-producing neurons in the brain. It is the second most common neurodegenerative disease after Alzheimer's and mainly affects people over 65. The three main motor symptoms are tremors, rigidity, and bradykinesia. Levodopa is the most effective treatment for the motor symptoms of Parkinson's but its efficacy decreases over time and is associated with motor complications. Other treatments include dopamine agonists, anticholinergics, COMT inhibitors, and deep brain stimulation. However, no treatment can slow or stop the progression of neuronal degeneration in Parkinson's.

1. PRESENTED BY-
NAVEEN KADIAN
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
K.L.E’S COLLEGE OF PHARMACY
BELGAUM-10

2. CONTENTS
• Introduction
• Epidemiology of PD
• Causes of Parkinsonism
• Risk factors of PD
• Clinical features of PD
• Treatment
• Reference

3. Definition
• Neurodegenerative disease is a condition which affects
brain function. Neurodegenerative diseases result from
deterioration of neurons.
• They are divided into two groups:
– conditions causing problems with movements
– conditions affecting memory and conditions related to
dementia.
– Examples:
• Alzheimer’s
• Parkinson’s
• Huntington’s
• Creutzfeldt-Jakob disease
• Multiple Sclerosis
• Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's
Disease)

4. Risk Factors
• Known
– Certain genetic
polymorphisms
– Increasing age
Possible
Gender
Poor education
Endocrine conditions
Oxidative stress
Inflammation
Stroke
Hypertension
Diabetes
Head trauma
Depression
Infection
Tumors
Vitamin deficiencies
Immune and metabolic
conditions
Chemical exposure
Smoking??

5. PARKINSON`S DISEASE is movement
disorder of unknown etiology due to
degeneration of neurons in the nigrostrial
dopamine system.
History:
First described in 1817 by an English physician,
James Parkinson, in “An Essay on the Shaking
Palsy.”
The famous French neurologist, Charcot, further
described the syndrome in the late 1800s.

6. Epidemiology of PD
The most common movement disorder
affecting 1-2 % of the general population over
the age of 65 years.
The second most common neurodegenerative
disorder after Alzheimer s disease (AD).

7. Causes of Parkinsonism
• Impaired release of dopamine- Idiopathic
parkinsonism.
• Drug depleting dopamine store-reserpine,
tetrabenzine.
• Toxin damaging dopaminergic neuron.
• Viral infection- Encephalitis ,Japanese encephalitis
• Trauma-repeated head injury[punch drunk syndrome]
• Miscellaneus-wilson disease,huntingtion,s disease

8. Dopamine pathways in human brain

9. Dopamine synthesis

10. Risk factors of PD
 Age - the most important risk factor
 Positive family history
 Male gender
 Environmental exposure: Herbicide and pesticide
exposure, metals (manganese, iron), well water, farming,
rural residence, wood pulp mills; and steel alloy
industries
 Race
 Life experiences (trauma, emotional stress, personality
traits such as shyness and depressiveness)?
 An inverse correlation between cigarette smoking and
caffeine intake in case-control studies.

11. Clinical features of PD
• Three cardinal
symptoms:
 resting tremor
 bradykinesia
(generalized
slowness of
movements)
 muscle rigidity

12. CLINICAL FEATURE
• TREMORS(4-6hz):
• tremors[pill rolling] at rest, decreases on action.
Usually first in finger/thumb.
• Coarse flexion/extension of finger[pill rolling &
drum beating]
• RIGIDITY-
• Cog wheel type especially in upper limb
{stiffness in all direction of movement}.
• Plastic type {lead type} mostly appreciated in
legs. In trunk rigidity manifest by flexed& stooped
posture

13. Hypokinesis
• Charactrized by poverty & slowness of
movement. Slowness in initiating
movement. Handwriting micrographia.
• GAIT-patient walk with short step , with a
tendency to run{as they are catching their
own centre of gravity}-festinating gait
• General-expressionless face with staring
look with infrequent blinking. Monotonus
speech. Dementia & Depression in
advance stage

14. Drugs used to treat Parkinson’s Disease

15. TREATMENT
• Anticholinergic drug- to relieve tremors.
• Dopamine agonist- bromocriptine&
pergolide.
• Amantadine-potentiate release of
dopamine.
• Selegeline : early stage, neuroprotective, delay
neuronal degeneration.
• Levodopa & carbidopa

16. Therapy of PD: levodopa
 Late 1950s: L-dihydroxyphenylalanine (L-DOPA;
levodopa), a precursor of DA that crosses the blood-brain
barrier, could restore brain DA levels and motor
functions in animals treated with catecholamine depleting
drug (reserpine).
 First treatment attempts in PD patients with levodopa
resulted in dramatic but short-term improvements; took
years before it become an established and succesfull
treatment.
 Still today, levodopa cornerstone of PD treatment;
virtually all the patients benefit.

17. Therapy of PD: limitations of levodopa
 Efficacy tends to decrease as the disease progresses.
 Chronic treatment associated with adverse events
(motor fluctuations, dyskinesias and
neuropsychiatric problems).

18. Inhibition of peripheral COMT by entacapone increases the amount
of L-DOPA and dopamine in the brain and improves the alleviation
of PD symptoms.

19. Therapy of PD: limitations of levodopa
 Does not prevent the continuous degeneration
of nerve cells in the subtantia nigra, the
treatment being therefore symptomatic.

20. Therapy of PD: Other treatments
DA receptor agonists:
Bromocriptine Pergolide

21. ropinirole
cabergoline

22. Anticholinergics:
Amantadine
AntiHistamines:
Diphenhydramine Orphenadrine
Selegiline

23. Antidepressant
Miscellanous:
imipramine
nortriptyline
Benzotropine
procyclidine

24. References
 BURGER’S Medicinal Chemistry & Drug discovery,6th
Edn,vol-1, Wiley-interscience publication
 CORWIN HANSCH, Comprehensive Medicinal
Chemistry,vol –IV 2008,Pregamon press
 Principles of Medicinal Chemistry by William O.Foye
 Medicinal Pharmacology by K.D Triphati.
 http:// www.cpharm.ucsf.edu/ kuntz/doct.html
 http:// www.bmm.icnet.uk/ ftdock/ftdoc.html
 www. Wikepedia.com
 www. Google.com
 www. Ipasp . com