Med chem PD

Question 1

symptoms of PD are induced by

Answer 1

1. depletion of intraneuronal dopamine stores
2. altering affinity of dopamine receptor for dopamine
3. increasing ACh levels
4. dopamine neurotoxins

Question 2

basic etiology of PD

Answer 2

dopamine deficiency

excess ACh

Question 3

what kind of receptors are dopamine receptors

Answer 3

GPCR

Question 4

dopamine pKa

Answer 4

10.6

protonated at physiological pH so it won’t cross BBB

Question 5

why is dopa’s pKa lower than dopamines

Answer 5

it is better able to stabilize a negative charge

Question 6

make up of GPCR

Answer 6

• 7 transmembrane helices
• alpha, beta, and gamma subunits
• alpha subunits determines its specific function

Question 7

agonist

Answer 7

• binds and stimulates receptor
• produces biologic response
• stabilizes active conformation

Question 8

partial agonist

Answer 8

• binds and stimulates receptor

- produces PARTIAL response

Question 9

antagonist

Answer 9

• binds receptor
• no biologic response
• prevents agonist binding

Question 10

inverse agonist

Answer 10

• binds receptor

- stabilizes inactive conformation

Question 11

agonists in terms of equilibrium

Answer 11

shifts equilibrium towards the active state

Question 12

inverse agonists in terms of equilibrium

Answer 12

shifts equilibrium towards the inactive state

Question 13

antagonists in terms of equilibrium

Answer 13

do not affect the equilibrium

Question 14

strategies for treating PD

Answer 14

1. restore lost dopamine
2. directly stimulate dopamine receptors (D2)
3. block glutamate
4. block acetylcholine’s effect through muscarinic receptors

Question 15

2 options for replacing dopamine deficiency

Answer 15

1. augment synthesis of dopamine in the brain

2. decrease dopamine catabolism

Question 16

how can we increase dopamine synthesis in the brain

Answer 16

inhibit dopa decarboxylase activity in the periphery

Question 17

drug that inhibits dopa decarboxylase activity in pheriphery

Answer 17

carbidopa

Question 18

side effects of inhibiting peripheral dopa decarboxylase

Answer 18

• GI disturbances
• activation of adrenergic and dopaminergic receptors
• hallucinations, psychosis

Question 19

how can we decrease dopamine catabolism

Answer 19

MAO-B inhibitors
COMT inhibitors
(reduce metabolism of L-dopa)

Question 20

pharmacophore of drugs that directly agonize dopamine receptors

Answer 20

• phenylethylamine structure

- carbon ring with 2 carbons separating it from the amine and an OH or NH in the meta position of the ring

Question 21

drug that blocks glutamate action at NMDA receptor

Answer 21

amatadine

Question 22

drugs that block acetylcholine’s effect through muscarinic receptors

Answer 22

• benztropine

- trihexyphenidyl