druggable targets

Question 1

what is a receptor?

Answer 1

a protein involved in the normal process of cell communication within an organism

Question 2

what can be a drug target?

Answer 2

-proteins: receptors, enzymes, transport proteins and ion transporters
-nucleic acids: DNA, RNA, and the ribosome
or miscellaneous e.g. antacids neutralise H+

Question 3

how do enzyme inhibitors work? give an example

Answer 3

interfere with the conversion of substrate into product.
example: acetylsalicylic acid acts cyclooxygenase, converting arachidonic acid into active lipid product that interacts with prostaglandins

Question 4

how do statins work?

Answer 4

simvastatin targets HMG-CoA reductase, competitively inhibiting it and interfering with de novo cholesterol synthesis

Question 5

how do enzyme false substrates work?

Answer 5

they are recognised by the enzyme due to similar structure, but generate an abnormal product

Question 6

how does a-methylDOPA work as a false enzyme substrate?

Answer 6

its coverted into a-methylnoradrenaline by DOPA decarboxylase/dopamine-B-hydroxylase

Question 7

what do transporters do?

Answer 7

bind the substrate and alter to make it active, whilst moving it across the membrane

Question 8

why are transporters required?

Answer 8

some molecules are too polar to permeate the membrane

Question 9

what is a symport?

Answer 9

where the transport of organic molecules is coupled to the transport of ions in the same direction

Question 10

what does a transporter false substrate do?

Answer 10

competes with normal substrate, leading to an accumulation of abnormal compound

Question 11

give an example of a transporter inhibitor

Answer 11

cocaine
binds to monoamine transporters, inhibiting transport of NTs, causing the presence of NT outside the cell to remain high for longer

Question 12

give an example of a transporter false substrate

Answer 12

amphetamine
transported into the noradrenaline/dopamine nerve terminal, causes extracellular NT to increase and increases NT release from vesicles

Question 13

in which ways can drugs affect ion channels?

Answer 13

• binding to the channel protein itself
• by indirect interaction involving a G protein and other intermediaries
• by altering the expression of ion channels on the cell surface

Question 14

how do ion channel blockers work?

Answer 14

they bind in the channel pore and affect ion permeation

Question 15

how do ion channel modulators work?

Answer 15

they bind to the ion channel and affect gating, they can have a positive or negative effect on permeation in response to a ligand

Question 16

what are ligand gated ion channels and what type of transmission are they responsible for?

Answer 16

a subfamily of ion channels that are regulated by the binding of a specific agonist to alter membrane permeability. they are involved in rapid transmission of a signal

Question 17

what is a pro-drug?

Answer 17

a drug which requires chemical or enzymatic modification before becoming active

Question 18

give an example of a pro-drug

Answer 18

enalapril - ACE converting enzyme inhibitor that is converted to the ACE inhibitor enalaprilat by cellular esterases

Question 19

give an example of a drug which inhibits a transporter

Answer 19

H+ pump inhibitor esomeprazole

Question 20

what is the difference between an ion channel blocker and an ion channel modulator?

Answer 20

blockers bind in the channel pore to affect ion permeation

modulators bind to the ion channel protein to affect gating

Question 21

what is an example of an ion channel blocker?

Answer 21

tetrodotoxin - voltage gated sodium channel blocker from a puffer fish

Question 22

what is an example of an ion channel modulator?

Answer 22

gliclazide - a sulfonylurea used in the treatment of diabetes type II. modulator of ATP sensitive potassium channels

Question 23

what is salbutamol?

Answer 23

a B2-adrenoceptor selective agonist

Question 24

what is a nuclear receptor?

Answer 24

a receptor for lipophilic signalling molecules. it can be located in the nucleus or the cytoplasm and act as transcriptional regulators

Question 25

what are examples of lipophilic signalling molecules?

Answer 25

• steroid hormones
• thyroid hormones
• vitamin D and retinoid acid
• fatty acidreceptors

Question 26

what are the main classes of cell surface receptors?

Answer 26

1- ligand gated ion channels
2- G protein coupled receptors
3- enzyme linked receptors

Question 27

what is a ligand gated ion channel?

Answer 27

a sub family of the ion channel superfamily that is regulated by binding of a specific agonist

Question 28

what do ligand-gated ion channels regulate?

Answer 28

ionotropic signalling in the nervous system. e.g. communication between neurones at synapses

Question 29

what is a nicotinic acetylcholine receptor?

Answer 29

a ligand-gated ion channel that is pentameric and found at the neuromuscular junction. it is made up of four different types of subunit (ax2, B,Y, omega). ACh binds to the extracellular domain of a-subunits only

Question 30

give an example of a nicotinic acetylcholine receptor agonist and antagonist

Answer 30

agonist - nicotine

antagonist - a-bungarotoxin