Antiparkinsonian Drugs

Dr. maged bin hariz

• Definition
 Parkinson's disease is a slowly progressive neurological disease →Degeneration of
nigrostriatal DA (Dopamine) neurons → ↓striatal DA & dominance of cholinergic
system
 Symptom of Parkinson's disease :
 Bradykinesia or akinesia (failure to initiate movement)- Tremors at reset- Rigidity-
postural instability.
 Causes of Parkinsonism (most common in the elderly)
 Idiopathic - Viral encephalitis
 Drug-Induced Parkinsonism:
o Antipsychotics → block D2 receptors.
o Reserpine → depletes DA stores.
o Methyldopa → inhibits DA synthesis.
 Antiparkinsonian Drugs
 Antiparkinsonian Drugs aim to restore DA/Ach balance

↑ Dopaminergic Activity ↓ Cholinergic Activity

Dopaminergic Drugs Anticholinergics.
• Levodopa/carbidopa. • Benztropine
• Bromocriptine (ergot) • Trihcxphcnidyl
• Pramipexole- ropinirol
(non-ergots)
• Amantadine.
• Entacapone.
 Antiparkinsonian Drugs
 Dopaminergic Drugs

 Levodopa (L-dopa) : (Mainstay of Therapy)

 L- dopa is a DA precursor that crosses BBB &is decarboxylated to DA in the CNS.
 It is given with the peripheral decarboxylase inhibitor, carbidopa, as Ldopa/
carbidopa (sinemet).
 Carbidopa : prevents peripheral decarboxylation of L-dopa to DA →↓ dose of
Ldopa by 75%.
 benefits of L-dopa decrease in a few years due to gradual neuronal degeneration
• Adverse Effects of L-dopa:
A. Peripheral (due to↑ DA peripherally;↓ DA with carbidopa)
 GIT: Nausea - vomiting .
 CVS: postural hypotension & arrhythmias
B. Central (due to ↑ DA centrally; ↓ DA with carbidopa)
 Dyskinesia.
 Confusion, hallucinations; psychosis.
C. Fluctuations in Response
 On-off effect (sudden swings from mobility to bradykinesia).
 Other Dopaminergic Drugs Used in Parkinsonism

Drug Mechanism of Action

Pramipexole - Ropinirole  Direct D2 agonists.

Bromocriptine- Apomorphine  Similar to L-dopa
Amantadine ↑ DA release (mild effect)
↓ DA reuptake
Selegiline Selective inhibitor of MAO-B (brain)
Entacapone COMT inhibitor(GIT , liver)

 Anticholinergics (Benztropine – Trihexphenidyl)

 Block central cholinergic activity
 restore DA/Ach balance.
Improve tremors (mainly)& rigidity, but less effective on bradykinesia.
 Used in:
 Drug induced Parkinsonism:
 Parkinson disease (especially in the young)
 Side Effects:
 Similar to atropine but less severe (dry mouth, constipation, confusion ).