Anti-Parkinsonism Drugs / Drugs Used in the treatment of Parkinson's Disease as per the PCI syllabus

2. PARKINSONISM DISORDER
“It is an extra pyramidal motor disorder”
Characterized by Rigidity, Tremor,
Hypokinesia, Defective posture, gait & Mask
like face. If untreated the patient become
rigid –unable to move & unable to breathe
properly“
Hypokinesia – loss of movement
Gait – walking pattern of human

4. It is a Progressive Degenerative Disorder
Mostly affects older people
Occurs due to the DEGENERATION OF NEURONS
AT SUBSTANTIA NIGRA PARS COMPACTA &
NIGROSTRIATAL (Dopaminergic) TRACT
Dopamine controls muscle tone and coordinates
movements
Parkinsonism disorder occurs due to the
deficiency of dopamine in the brain,

7. ANTI-PARKINSONISM DRUGS
“DRUGS USED TO TREAT PARKINSONISM
DISORDER”

8. CLASSIFICATION:
DRUGS AFFECTING BRAIN DOPAMINERGIC SYSTEM
 DOPAMINE PRECURSOR
LEVODOPA
 PERIPHERAL DECARBOXYLASE INHIBITORS
CARBIDOPA
BENSERAZIDE
 DOPAMINERGIC AGONIST
BROMOCRIPTINE
ROPINIROLE
PRAMIPEXOLE
 MAO-B INHIBITOR
SELEGILINE
 COMT INHIBITORS
ENTACAPONE
TOLCAPONE
 DOPAMINE FACILITATOR
AMANTADINE

9. DRUGS AFFECTING BRAIN CHOLINERGIC SYSTEM
 CENTRAL ANTICHOLINERGICS
TRIHEXYPHENIDYL(BENZHEXOL)
PROCYCLIDINE
BIPERIDEN
 ANTIHISTAMINICS
ORPHENADRINE
PROMETHAZIN

10. DRUGS AFFECTING BRAIN DOPAMINERGIC SYSTEM:
DOPAMINE PRECURSOR:
Eg: Levodopa
Also known as L-dopa.
It is inactive by itself, but It is the precursor of
DOPAMINE.
It has salutary effect in PD
LEVODOPA (Within the brain)
converted to
DOPAMIN

11. More than 95 % of oral dose is decarboxylated
in peripheral tissues.(Gut and liver)
1-2 % of administered Lavadopa crosses Blood
Brain Barrier (BBB) and reaches the brain.
It is taken up by the surviving dopaminergic
neurons and converted to DOPAMINE, which is
stored and released as a neurotransmitter,
Peripherally formed dopamine produces some
unwanted effects.

12. MECHANISM OF ACTION:
LEVODOPA
1-2 % crosses BBB & reaches brain

Taken up by surviving Dopaminergic neuron in Brain
 Converted into
Dopamine
 This is
Stored and released as Neurotransmitter

Binds to dopamine receptor
 Resolves
Rigidity, Hypokinesia, Tremor, Defective posture

Anti Parkinsonism activity

13. PHARMACOKINETICS
Rapidly absorbed from small intestine
Undergoes high first pass metabolism
t1/2 – 1 to 2 hours
Metabolized by conjugation in liver
Excreted in urine

14. ADR
AT INITIAL THERAPY Nausea
– Vomiting
– Postural hypertension (A form of low blood
pressure that happens when standing up from
sitting or lying down.)
– Cardiac arrhythmia
AFTER PROLONG THERAPY
- Abnormal movements
USES
Used in the treatment of Parkinsonism disorder.

15. PERIPHERAL DECARBOXYLASE INHIBITOR
CARBIDOPODA AND BENZERAZIDE
• They are extra cerebral “Dopamine
Decarboxylase Inhibitors”
• They do not penetrate BBB and do not inhibit
the conversion of Levodopa  Dopamine in
brain
• Mostly administered along with levadopa
• CARBIDOPA + LEVODOPA is known as
- CO CARELDOPA

16. MECHANISM OF ACTION:
LEVADOPA + CARBIDOPA

CARBIDOPA PREVENTS THE DECARBOXYLATION OF
LEVADOPA IN PERIPHERAL TISSUES

MORE AMOUNT OF LEVADOPA CROSSES THE BBB

 MORE LEVADOPA IS CONVERTED IN TO
DOPAMINE IN BRAIN

MORE IMPROVED ANTI-PARKINSONISM ACTIVITY

17. DOPAMINERGIC AGONISTS:
Dopamine agonist can act on striatal dopamine
receptors and activate it
Produce long duration of action
Eg: Bromocriptine, Ropinirole
It is an ergot derivative
Potent Dopamine D2 receptor agonist
Partial agonist / antagonist on Dopamine D1
receptor
Improvements in parkinsonian symptoms
occurs within half to one hour of an oral dose of
bromocriptine

18. Action lasts for 6-10 hours
It has been largely replaced by the newer
Dopamine agonists Ropinirole and Pramipexole
MECHANISM OF ACTION:
BROMOCRYPTINE

BINDS TO DOPAMINE D2 RECEPTOR PRESENT IN
THE BRAIN

PRODUCES AGONIST ACTION

ANTI- PARKINSONISM ACTIVITY

19. PHARMACOKINETICS
Used alone
High dose needed
Expensive
ADR
Nausea
Vomiting
Postural hypertension
Insomnia

20. MONOAMINE OXIDASE-B INHIBITORS
(MAO-B INHIBITORS):
Eg: SELEGILINE
Selegiline also known as – DEPRENYL
It is a selective , irreversible inhibitor of MAO-B
(Monoamine Oxidase-B)
MAO-B present in brain
MAO-B involved in the breakdown of Dopamine
in brain
Selegiline always administered with Levadopa
It prolongs the action of Levadopa

21. MECHANISM OF ACTION:
SELEGILINE

SELECTIVELY & IRREVERSIBLY INHIBIT THE ENZYME
MAO-B IN BRAIN

IT PREVENTS THE BREAKDOWN OF DOPAMINE IN
BRAIN
 LEADS TO
ACCUMULATION OF DOPAMINE IN BRAIN

RESOLVES PARKINSONISM EFFECTS

ANTI- PARKINSONISM ACTIVITY

22. PHARMACOKINETICS:
Selegiline is readily absorbed from the gastro
intestinal tract.
It is distributed rapidly into the tissues, including
the brain.
Selegiline is metabolized in the liver.
The metabolites of selegiline were excreted in
urine
ADR
Postural hypotension
Nausea
Confusion
Convulsion

23. COMT INHIBITORS
Entacapone & Tolcapone are the drugs which
selectively and reversibly inhibit the enzyme
COMT (Catechol-O-methyl transferase)
It have been introduced as adjuvant to
levadopa - carbidopa for advanced PD
COMT plays a major role in the
Degradation of levadopa to 3-O-
methyldopa (in Periphary)
Degradation of dopamine in brain

24. MECHANISM OF ACTION:
TOLCAPONE, ENTACAPONE

INHIBIT THE ENZYME COMT

PREVENTS THE DEGRADATION OF LEVEDOPA TO 3-
OMD

PROLONGS THE t1/2 OF LEVADOPA

LARGER FRACTION OF ADMINISTERED DOSE
CROSSES THE BBB AND REACHES BRAIN

ANTI- PARKINSONISM ACTIVITY

25. ADR:
Nausea
Vomiting
Dyskinesia
Postural hypotension (it is a type of low BP
when u are standing up from sitting or lying
down)
Hallucinations
Diarrhea

26. DOPAMINE FACILITATOR:
It is also known as
– GLUTAMATE ANTAGONIST
– NMDA RECEPTOR ANTAGONIS
Eg: AMANTADINE
 Developed as anti viral drug for prophylaxis
of influenza A2
 It was found serendipitously to benefit
Parkinsonism
 It acts rapidly but has lower efficacy than
levodopa

27. • Tolerance develops over months & efficacy is
gradually lost
• It promotes pre synaptic synthesis and
release of dopamine in the brain
• Also it act by antagonizing the NMDA type of
glutamate receptors
• It can be used in milder cases

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