Drug Discovery

Question 1

What are ionotropic receptors

Answer 1

Ligand-gated ion channels
Charged ions move in or out of the cell to make the cell more
-positively charged
-negatively charged

Question 2

What are metabotropic receptors

Answer 2

G-protein coupled receptors
Receptors activate intracellular signals that
-activate other intracellular signalling cascades
-activate ion channels

Question 3

Name fast neurotransmitters that act on ligand-gated ion channels

Answer 3

Glutamate- main excitatory
GABA- main inhibitory
Acetylcholine

Question 4

Name slow neurotransmitters that act on GPCRs

Answer 4

Dopamine
Serotonin
Noradrenaline

Question 5

Challenges with drug design in the CNS

Answer 5

-receptors are expressed through the brain
-the brain is protected by the blood brain barrier
-placebo effect

Question 6

How to design selective drugs

Answer 6

-have the correct functional groups for binding interactions
-have those binding groups correctly positioned
-be the right size

Question 7

Outline the binding interactions

Answer 7

Strong enough for ligand to bind, weak enough to allow it to leave

Question 8

Outline the position of the functional groups

Answer 8

Functional groups in the correct relative position
Chiral molecule - enantiomer

Question 9

Outline the blood brain barrier

Answer 9

Prevents pathogens getting into the brain
Lies at the interface between the blood capillaries of the brain and brain tissues
Endothelial cells are tightly packed together- surrounded by astrocytes and pericytes
Efflux transporters pump undesired compounds out of the BBB

Question 10

What happens to drugs that have high lipophilicity

Answer 10

Poor stability and metabolic stability

Question 11

What happens to drugs that are too hydrophobic

Answer 11

Wont dissolve in blood or gastrointestinal fluid

Question 12

What is a prodrug

Answer 12

A compound that has no activity in its administered form and that is converted to its active form inside the body- crossed the BBB

Question 13

Dopamine replacement for Parkinson’s

Answer 13

Dopamine cannot cross the BBB
Levodopa is a prodrug for dopamine
Uses the transport protein for the amino acid phenylaline to cross the blood brain barrier
Converted to dopamine once in the brain by DOPA decarboxylase

Question 14

Outline carbidopa

Answer 14

Stops l-DOPA being broken down before reaching the brain, cant cross the BBB

Question 15

Outline Monoamine oxidase inhibitors

Answer 15

Dopamine is metabolised by this enzymes
Inhibition of this enzyme can prevent degradation and lead to an increase of extra cellular dopamine

Question 16

How to measure lipophilicity of drugs

Answer 16

Partition coefficient describes the lipophilicity/hydrophillic nature of a compound
Measure the relative distribution of the compound in an n-octanol/water mixture, expressed as log P
Hydrophobic drugs prefer to dissolve in the n-octanol (high P)
Hydrophillic drugs prefer to dissolve in water (low P)

Question 17

Which drugs prefer to dissolve in high P

Answer 17

Hydrophobic drugs in n-octanol

Question 18

Which drugs prefer to dissolve in low P

Answer 18

Hydrophillic drugs in water