Introduction
Parkinsonism is a chronic neurological disorder caused by loss of dopamine-producing neurons in the substantia nigra. This dopamine deficiency leads to the classic symptoms: tremors, rigidity, slow movements and postural imbalance. Drug therapy focuses on restoring dopamine levels or balancing dopamine and acetylcholine activity in the brain. Current medicines improve symptoms but do not cure the disease.
1. Levodopa and Carbidopa
Levodopa (L-Dopa) is the most effective drug for Parkinsonism. Dopamine cannot cross the blood–brain barrier, but levodopa can. Inside the brain, it is converted into dopamine and improves movement.
Why Carbidopa Is Added?
Carbidopa inhibits peripheral dopa decarboxylase, preventing levodopa breakdown in the intestines and tissues. This allows more levodopa to reach the brain and reduces side effects such as nausea and vomiting.
Actions
- Reduces tremors, rigidity and bradykinesia
- Improves mobility and quality of life
Major Problems with Long-Term Use
- On-off phenomenon: sudden changes between mobility and immobility
- Dyskinesias (involuntary movements)
- Effect reduces after 3–5 years due to progressive neuron loss
Side Effects
- Nausea, vomiting, anorexia
- Postural hypotension, tachycardia
- Hallucinations, mood changes, psychosis
- Brownish discoloration of urine or saliva
Interactions
- Vitamin B6 increases levodopa breakdown
- MAO inhibitors may cause hypertensive crisis
- Antipsychotics reduce effectiveness
2. MAO-B Inhibitors (Selegiline & Rasagiline)
Selegiline and rasagiline block monoamine oxidase-B, the enzyme that breaks down dopamine in the brain. This increases dopamine availability and enhances the effect of levodopa.
Advantages
- Reduce “wearing-off” effect of levodopa
- Allow lowering levodopa dose
Side Effects
- Insomnia (selegiline → metabolized to amphetamine-like products)
- Headache, confusion
- Risk of hypertension at high doses
3. COMT Inhibitors (Entacapone & Tolcapone)
These drugs block catechol-O-methyltransferase (COMT), an enzyme that converts levodopa to inactive metabolites.
Benefits
- Increase levodopa levels in the brain
- Reduce “wearing-off” symptoms
Important Differences
- Entacapone: safer, short acting
- Tolcapone: long acting but may cause fatal liver damage
Side Effects
- Diarrhoea
- Postural hypotension
- Dyskinesias
- Hallucinations, confusion
4. Dopamine Receptor Agonists
Drugs like bromocriptine, pramipexole, ropinirole, rotigotine and apomorphine directly stimulate dopamine receptors.
When Are They Useful?
- Early Parkinsonism to delay levodopa need
- Advanced cases with motor fluctuations
- Patients who cannot tolerate levodopa
Advantages
- Longer duration of action
- Lower risk of dyskinesias compared to levodopa
Side Effects
- Hallucinations, confusion, insomnia
- Nausea, vomiting
- Postural hypotension
- Impulse control disorders (rare)
5. Amantadine
Amantadine is an antiviral drug accidentally found to improve Parkinson symptoms.
Mechanism
- Increases dopamine release
- Blocks NMDA glutamate receptors
- Mild anticholinergic effect
Best For
- Bradykinesia
- Rigidity
- Levodopa-induced dyskinesias
Side Effects
- Confusion, agitation, hallucinations
- Ankle swelling
- Livedo reticularis (mottled skin)
- Dry mouth, urinary retention
6. Antimuscarinic Agents
Examples: Benztropine, Trihexyphenidyl, Procyclidine, Biperiden.
Role in Therapy
- Helpful in tremor-dominant Parkinsonism
- Useful in younger patients
- Less effective for rigidity and bradykinesia
Side Effects
- Dry mouth, constipation, urinary retention
- Blurred vision, mydriasis
- Confusion in elderly
Detailed Notes:
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