Basal Ganglia Drugs

Question 1

D1 and D2 Rs

Answer 1

D1 on GABA neurons in striatum that project to direct pathway. Stimulated by DA.
D2 on GABA neurons projecting to indirect. Inhibited by DA

Question 2

Parkinson’s

Answer 2

Loss of DAergic neurons from SN, so lose activation of direct pathway and inhibition of indirect

Question 3

2 Enzymes of DA Synth

Answer 3

Tyrosine hydroxylase converts tyr to Dopa, and Dopa decarboxylase converts Dopa to DA

Question 4

2 Enzymes of DA Degradation

Answer 4

COMT and MAO. Can switch positions

Question 5

Carbidopa (what it is and 2 effects)

Answer 5

Inhibitor of Aromatic L-AA decarboxylase, enzyme that converts L-Dopa to DA.
1. Increases drug in circulation bc stays as L-Dopa (form that can cross BBB
2. Reduces side effects bc less exogenous DA in periphery
Overall can lower the dose and have fewer side effects

Question 6

4 Problems of PD Treatments

Answer 6

Dietary AAs compete w/ L-Dopa for transport from gut to circulation and circ into brain, so don’t take w/ meals
GI problems and cardiac problems from periphery, so take w/ carbidopa
Degeneration of neurons continues and effectiveness of LDopa declines

Question 7

3 Other PD D Drugs

Answer 7

Pergolide: D1 and 2 agonist
Bromocriptine: D2 agonist, restores indirect inhibition
Ropinirole: D2 agonist

Question 8

Ach in Striatum

Answer 8

M1/M4 stimulate GABAs going to direct, M1 stimulates GABAs going to indirect

Question 9

3 Ach PD Drugs

Answer 9

Benztropine: AChR antagonist
Trihexyphenidyl: M1 muscarinic R antagonist
Biperiden: M1 R antagonist

Question 10

Huntington’s Disease

Answer 10

Loss of GABAergic neurons in BG. Ones going to indirect pathway loss first so get hyperactivity

Question 11

2 HD Drugs

Answer 11

Haloperidol - block DA Rs

Dizepam - enhance GABA Rs