Biogenic Amine Theory of Parkinsonism and Antiparkinson Drugs

Biogenic Amine Theory of Parkinsonism

• The biogenic amine theory of Parkinsonism posits that Parkinson's disease (PD) is primarily due to a deficiency of dopamine in the brain, particularly in the basal ganglia. The degeneration of dopaminergic neurons in the substantia nigra leads to reduced dopamine levels in the striatum, disrupting motor control and causing symptoms such as tremors, rigidity, bradykinesia, and postural instability.

Classification of Antiparkinson Drugs

• Dopamine Precursors (Levodopa)
• Dopamine Agonists (Pramipexole, Ropinirole)
• Monoamine Oxidase B Inhibitors (Selegiline, Rasagiline)
• Catechol-O-Methyltransferase (COMT) Inhibitors (Entacapone, Tolcapone)
• Anticholinergic Drugs (Benztropine, Trihexyphenidyl)
• Amantadine

1. Dopamine Precursors (Levodopa)

• Mechanism of Action: Levodopa is a precursor to dopamine and crosses the blood-brain barrier, where it is converted into dopamine to compensate for the deficiency in Parkinson’s disease.
• Therapeutic Uses: Levodopa is used as the primary treatment for motor symptoms of Parkinson's disease.
• Adverse Effects:
• Nausea, vomiting, orthostatic hypotension
• Dyskinesias, motor fluctuations (on-off phenomena)
• Wearing-off effect with long-term use
• Contraindications: Contraindicated in patients with narrow-angle glaucoma and psychiatric disorders.

2. Dopamine Agonists (Pramipexole, Ropinirole)

• Mechanism of Action: Dopamine agonists directly stimulate dopamine receptors in the brain, bypassing the need for dopamine production.
• Therapeutic Uses: Used as monotherapy in early Parkinson's disease or as an adjunct to Levodopa.
• Adverse Effects:
• Nausea, dizziness, somnolence
• Impulse control disorders (e.g., gambling, hypersexuality)
• Peripheral edema, hallucinations in the elderly
• Contraindications: Use with caution in patients with severe cardiovascular disease or psychiatric conditions.

3. Monoamine Oxidase B Inhibitors (Selegiline, Rasagiline)

• Mechanism of Action: MAO-B inhibitors prevent the breakdown of dopamine by inhibiting the enzyme monoamine oxidase B, increasing dopamine levels in the brain.
• Therapeutic Uses: Used as adjuncts to Levodopa therapy in Parkinson’s disease to reduce motor fluctuations.
• Adverse Effects:
• Headache, insomnia, dizziness
• Hypertensive crisis if combined with tyramine-rich foods
• Contraindications: Contraindicated in patients taking SSRIs or tricyclic antidepressants due to risk of serotonin syndrome.

4. Catechol-O-Methyltransferase (COMT) Inhibitors (Entacapone, Tolcapone)

• Mechanism of Action: COMT inhibitors increase Levodopa's half-life by blocking the enzyme catechol-O-methyltransferase, which normally metabolizes Levodopa.
• Therapeutic Uses: Used in combination with Levodopa to reduce wearing-off phenomena and prolong its action.
• Adverse Effects:
• Diarrhea, liver toxicity (especially with tolcapone), orange-colored urine
• Contraindications: Contraindicated in patients with liver disease or cardiac arrhythmias.

5. Anticholinergic Drugs (Benztropine, Trihexyphenidyl)

• Mechanism of Action: These drugs block muscarinic receptors and help restore the balance between acetylcholine and dopamine in the basal ganglia.
• Therapeutic Uses: Effective for controlling tremors, especially in younger Parkinson’s patients.
• Adverse Effects:
• Dry mouth, blurred vision, constipation
• Urinary retention, confusion (in elderly patients)
• Contraindications: Contraindicated in patients with glaucoma, urinary retention, or intestinal obstruction.

6. Amantadine

• Mechanism of Action: Amantadine increases dopamine release, inhibits its reuptake, and has mild NMDA receptor antagonism.
• Therapeutic Uses: Used in early Parkinson’s disease and for managing dyskinesias in Levodopa therapy.
• Adverse Effects:
• Livedo reticularis, nausea, insomnia
• Confusion, especially in elderly patients
• Contraindications: Caution in patients with renal impairment or congestive heart failure.