-Direct pathway (movement- enabling) is understimulated 

-Underinhibition of indirect pathway (movement-inhibiting)

First sx- 70% neurons destroyed

Autopsy-95% neurons destroyed

Sx of disease: bradykinesia, rigidity, impaired postural balance, tremor

only treats sx

incerases dopamine activity in brain

Class: Dopamine precursor

Clinical app: use another class first, and then add this on

MAE: precursor so is readily transported across BBB (dopamine cant)

A/E: nausea due to conversion in GI, tolerance and desensitization, dyskinesia

PK:1-3% reaches CNS when alone,administered with carbidopa, does not cross BBB so levodopa can be converted after crossing BBB

Dosing: requires higher doses as pt has been on longer

Class:Dopamine Receptor Agonists

MOA:Directly target postsynaptic DA receptors

pk:no enzymatic conversion required, longer half-life than levodopa (less blood level fluctuations)

A/e: sedation vivid dreams, hallucinations

Selegiline, rasalagine

Inhibitors of dopamine and/or L-DOPA metabolism

- MAOB inhibitors

-doesn't interfere with MAO-A metab

Metabolite is amphetamine- POSSIBLY TOXIC

COMT inhibitors (enzyme that breaks down dopa)

Entacapone works peripherally only

increase levels of levodopa

COMT inhibitors (enzyme that breaks down dopa)

A/e: Hepatotoxicity

Class: Non-dopaminergic agents

MAE: unknown

Clinical use: treatment of levodopa induced dyskinesias

Class: non-dopa agent

Use: Reduction of tremor

receptor: muscarnic receptor antagonist

A/E:ANTICHOLINERGIC