Dopaminergic pathways

Question 1

Dopaminergic pathways

1) Behavior, emotion, “feelings”
2) Coordination of movement, posture
3) Release of pituitary hormones
4) Nausea and vomiting

Answer 1

1) Mesolimbic
2) Nigrostriatal
3) Hypothalamus and pituitary
4) Chemo-receptor triggerzone

Question 2

Levadopa

Answer 2

Use: treat parkinsons
Mechanism: Supplies substrate for dopamine synthesis in the neuron

Short duration of action

**Can cause dopamine poisoning: Nausea/vomiting, dyskinesias, arrhythmias

Drug interactions: non-specific MAO inhibitors = hypertension, antipsychotic drugs and antimimetics = block DA receptors, Anticholinergic drugs = delay gastric empying

Question 3

Carbidopa

Answer 3

Use: In conjuction with Levadopa to reduce toxicity.

Mechanism: Decarboxylase Inhibitor. Does NOT cross blood brain barrier

No effect by itself, less DA (dopamine) formed peripherally
(because it inhibits the peripheral enzymes that break it down)

(so Carbidopa allows less levadopa to be administered since normally decarboxylase in gut/etc break it to dopamine and only 1-3 percent reach brain, requiring high/dangerous does…now it will break down to dopamine mostly in the brain)

Question 4

Entacapone (Comtan)

Answer 4

Use: reduce wearing off effect during levodopa/carbidopa treatment

Mechanism: Inhibit COMT reducing levodopa metabolism

Question 5

**Selegiline

Answer 5

• *Use: Treatment of Parkinsons
• **Mechanism: Inhibiting “MAO-B” (Dopamine Breakdown in brain)
• *-Life threatening if taken too large of a dose w/ levadopa (probably because too much dopamine)

**-Metabolites = amphetamines and methamphetamines

Question 6

Bromocriptine
Pramipexole
Ropinisole

Answer 6

Use: treatment of parkinsons
Mechanism: Dopamine Receptor AGONIST
Well absorbed and Longer duration of action
Adverse effects: expected DA agonist effects (same as levadopa)
**Bromocriptine is used to treat amenorrhea-galactorrhea

Question 7

Apomorphine

Answer 7

Use: Used for rescue treatment of patients experiences severe bradykinesias

Mechanism: DA Agonist

Often severe adverse effects of excess DA

Question 8

Amantadine

Answer 8

Use: treatment of parkinsons

*Mechanism: Stimulates release of DA

Used in early states of disease as effects often disappear w/ progression (I think since it relies on neurons to be alive)

*Well absorbed and excreted

Question 9

Benztropine

Answer 9

**Uses: treatment of idiopathic parkinsonism

**Mechanism: Inhibit cholinergic neurotransmission in the striatum

**Useful for antipsychotic drug induced parkinsonism