1. Parkinson's disease 2. Types 3. Anti-Parkinsonism drugs types 4. synthesis of L-DOPA

1. 2.5 Antiparkinsonism Drugs
M R . P R A V I N B E N D L E
A S S I S T A N T P R O F E S S O R
N . G . A C H A R Y A A N D D . K . M A R A T H E C O L L E G E C H E M B U R

2. Parkinson's disease
It is named after Dr. James Parkinson, who first described the
diseased condition called the 'shaking palsy’.
Parkinson's disease is due to abnormalities of the central nervous
system (CNS) and malfunctioning of the lower part of the brain.
It mainly causes rigidity in the body, affects the posture, movement
and speech.

3. https://www.webmd.com/parkinsons-disease/guide/parkinsons-causes#1
Depletion of dopamine in the brain is the main
cause in the patient having Parkinson's disease.

4. Types of Parkinson's disease

5. Symptoms of Parkinson’s Disease
Tremor at rest & is most common in the hands and arms. As the disease progresses the tremor may
affect more of the body & /or become more pronounced.
Rigidity or muscle stiffness causes unstable posture & awkward gait.
Slow movement or Bradykinesia: It is associated with the inability to start a movement, also causes a
shuffling walk.
Due to stiffening of muscles , there will be difficulties in eating and swallowing as well as slurred speech.
It may also affect bowel and bladder movement and control.
In acute conditions the facial muscles freeze resulting in mask -like facial expression.

6. Anti-Parkinsonism drugs
“The drugs used for treatment of Parkinson's disease & alleviate the symptoms are called anti-Parkinsonism
drugs.”
The changes taking place in the body due to the disease cannot be usually reversed.
The drugs used can only alleviate the symptoms & allow the patient to live with lesser difficulties. However,
the disease cannot be completely cured.
The impulses are transmitted at the nerve ends by means of chemical neurotransmitters.
The anti Parkinsonism drugs function by antagonising these chemical transmitters and thus block the origin
of tremors

7. TYPES OF ANTI-PARKINSONISM DRUGS
Anticholinergic Agents
They antagonize the cholinergic agents which stimulate the para sympathetic
nervous system.
Belladona alkaloids e.g. atropine and hyoscine.
Dopaminergic Agents
Depletion of Dopamine (neurotransmitter) is associated with clinical
condition of Parkinson's disease.
The compounds which are able to replenish dopamine in CNS or themselves
act as anti-Parkinsonism drugs are called dopaminergic agents.

8. TYPES OF ANTI-PARKINSONISM DRUGS
Anticholinergic Agents
• Classification
• Procyclidine hydrochloride [pyrrolidine derivative]
• This drug is used for symptomatic treatment of post
encephalitic Parkinsonism.
• Ethopropaine hydrochloride [Phenothiazine derivative]
• This drug is used for management of Parkinson's disease,
particularly for the control of rigidity.
• It is also used for reducing spasm, tremor and oculogyration.
CH3
C
H2
N
S
CH N
C2H5
C2H5
.HCl

9. DOPAMINERGIC AGENTS
Levodopa (a-Amino acids):
When levodopa is administered, it can penetrate the blood-brain barrier (BBB) & get
decarboxylated to give dopamine. Thus, it can replace dopamine in the brain, which is
depleted in the patient having Parkinson's disease. It is also used to control similar
neurological symptoms caused by manganese poisoning.
O
H
O
H
CH2 CH COOH
NH2
Levodopa
O
H
O
H
CH2 CH2 NH2
Dopamine
-CO2

10. Synthesis of Levodopa
Levodopa (L-isomer) : It belongs to the amino acid class of compounds.
Use: It is the commonly used anti-Parkinsonism drug. It helps to reduce rigidity &
tremors and increases the alertness of patients.
Side effects: Causes nausea, vomiting and cardiac arrhythmia
O
H
O
H
CH2 CH COOH
NH2
Levodopa

11. O
H
H3CO
CHO + CH2 COOH
NH2
Vanillin Glycine
Condensation
O
H
H3CO
CH C COOH
NH2
Reduction
[2H]
O
H
H3CO
CH2 CH COOH
NH2
DL-mixture
(CH3CO)2O
Ac= CH3CO
AcO
H3CO
CH2 CH COOH
NH2
DL-mixture
Resolution by α -phenyl ethyl amine
Hydrolysis by HBr
-2CH3COOH,-
CH3Br
O
H
O
H
CH2 CH COOH
NH2
Levodopa
Synthesis of Levodopa

12. • Vanillin is
condensed with
glycine
The product is
reduced to get
methylated dopa
(DL-mixture)
This is acetylated
& then the racemic
mixture is resolved
by a-phenyl ethyl amine
to get L-isomers.
Finally it is hydrolysed
by HBr.
O
H
H3CO
CHO + CH2 COOH
NH2
Vanillin Glycine
Condensation
O
H
H3CO
CH C COOH
NH2
Reduction
[2H]
O
H
H3CO
CH2 CH COOH
NH2
DL-mixture
(CH3CO)2O
Ac= CH3CO
AcO
H3CO
CH2 CH COOH
NH2
DL-mixture
Resolution by α -phenyl ethyl amine
Hydrolysis by HBr
-2CH3COOH,-
CH3Br
O
H
O
H
CH2 CH COOH
NH2
Levodopa
Ac

13. This Photo by Unknown Author is licensed under CC BY-SA
Reference : Synthetic drugd & dyes by Himalaya publication