Neuro-Drug Targets Flashcards Preview

Pharmacology > Neuro-Drug Targets > Flashcards

Flashcards in Neuro-Drug Targets Deck (40):
1

What are the major five classes of drug targets

1) Membrane receptors
2) Nuclear receptors
3) Ion Channels
4) Transport Proteins
5) Enzymes

2

What is the very basic order of membrane receptors signal transduction

1) Ligand binds
2) Membrane receptors are bound
3) Intracellular signaling intermediates
4) Cellular response

3

What is the most common membrane protein drug target

GCPR

4

What is the target of dobutamine

B1 agonist

5

What is the process of down-regulation in GCPRs

When a true triggers activity in the G protein, it will illicit the result, however over time, as the drug remains, the effect will become desensitized

6

What the result of a patient on Beta blockers over time that suddenly stops

The presence of a beta bloacker will lead to the up regulation of the B2 receptor, but the beta blocker will keep from ever seeing a result. If the patient suddenly stops, they become very sensitive to NE with devastating responses

7

What must all transcription factors contain

DNA binding segment

8

Where do transcription factors usually bind

Promoters or enhancing regions that are adjacent to the coding region of the regulated gene

9

What is the specific region that a transcription factor will bind to

Response elements

10

What usually occurs at the N-terminal of the GCPR

Glycosylated

11

Where is the N terminal located in the GCPR

Extracellular portion

12

Where is the C terminal of the GCPR located

Cytosol

13

What usually occurs at the C terminal of GCPR

Phosphorylated at serine/threonine sites)

14

What portion of the GCPR contains the G protein binding sites

Cytoplasmic loops

15

Which region of the GCPR usually interacts with cytoplasmic regions upon ligand binding

Third cytoplasmic loop connecting regions 5 and 6

16

What is the event with GCPR that can lead to receptor endocytosis

Phosphorylation of the terminal serine and threonine hydroxyl sites

17

What is the process of ligand binding causing the activation of the GCPR

1) Ligand binds and activates the heterotrimeric G protein by the receptor
2) GDP is released and GTP is able to bind
3) GTP bound state is able to activated enzymes/channel
4) GTP is cleaved to GDP in order to deactivate the GCPR

18

The Gs family of GCPR activates which enzymes

All adenyl Cyclase and Src Tyrosine kinases

19

What group of enzymes are affected by the Gi family of GCPR

Inhibition of adenylyl cyclase, but will activate Src tyrosine kinase

20

What enzymes are affected by the Gq family of GCPR

Phospholipase Cbeta

21

Activation of phosphodiesterase results in what effect

Breakdown of cAMP and reduction of downstream results

22

What is the result of increase in catalytic subunits

Phosphorylation and activation of response elements

23

What is the result of an increase in phophatase activity

Removal of phosphates and decrease actions of response elements

24

What is the result of an increase in PLC activity

Increase production of IP3 and DAG from PIP2 leading to more activation

25

What is the result of increased activity of PKC

Increased phosphorylation of substrates leading to more of a response

26

What are the characteristics of lipophilic drugs with regards to onset and elimination

Onset is delayed, but the effects can persist after the drug has been eliminated

27

What is the mechanism of action of steroid drugs

1) DNA binding region of receptor is bound by HSP90
2) Drug binds to the ligand binding site, removing HSP90
3) Receptor becomes activated and can affect transcription

28

What type of NT is acetylcholine

Excitatory

29

What type of NT is glutamate

Excitatory

30

What type of NT is GABA

Inhibitory

31

What type of NT is Glycine

Inhibatory

32

How doe excitatory NTs work

Open cation channels that cause deoplarization

33

How do inhibitory NTs work

Open anion channels and move away from threshold, hyper-polarize the cells

34

Binding and activation of nAchR leads to influx of which ion

Sodium

35

Binding and activation of GABA receptors allows the flow of which ion

Calcium influx and hyperpolarization

36

GABA receptors are the targets for which drugs

-General anesthetics
-Hypnotic and anti anxiety
-ethanol

37

What does the SH2 domain bind to

Phosphotyrosines

38

What does the SH3 domain bind to

Phosphoprolines

39

What is the process of activation of a tyrosine kinase leading to downstream

1) TK dimerizes leading to phosphorylated tyrosine
2) P-tyrosines bind to SH2 on Grb2
3) SH3 on Grb2 binds to SOS (a GEF)
4) SOS moved from RAS-GDP to RAS-GTP

40

What is the effect on the level of ENaC and Na/K ATPase with the administration of spironolactone

Decreased expression