Pathophysiology of

Parkinsonism

Etiology

• Disease is correlated with destructuion of dopaminergic neurons in the substantia nigra with consequent reduction of dopamine actions in the corpus striatum.– The loss of dopamine neurons in the substantia

nigra is evidenced by diminished uptae of dopamine precursors in this region.

Substantia nigra

• Part of the extrapyramidal system• Source of dopaminergic neurons that

terminate in the striatum– Each dopaminergic neuron makes synaptic

contacts within the neostriatum, and modulates the activity of cells .

– Dopaminergic system appears to serve as a tonic, sustaining influence on motor activity rather than participating in specific movements.

Neostriatum

• In Parkinson’s disease, destruction of cells in the substantia nigra results in the degeneration of the nerve terminals responsible for secreting dopamine in the neostriatum– Thus, the normal modulating inhibitory influence of

dopamine on cholinergic neurons in the neostriatum is diminished, resulting in overproduction acetylcholine by the stimulatory neurons

Classification of antiparkinsonicdrugs, agents

1. Levodopa - Levodopa + Carbidopa

2. Dopamine agonists− Bromocriptine− Pramipexole− Ropinirole

3. NMDA– Amantadine

4. MAO B inhibitors – Selegiline– Rasagiline

5. COMT inhibitors– Entacapone– Tolcapone

6. Anticholinergic grugs ( antimuscarinic ) – Benzotropine– Trihexyfenidyl

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