Principles of Neurupharmacology

Question 1

What are the 4 components of the BBB?

Answer 1

• microvascular endothelial cells
• pericytes
• the capillary basement membrane
• astrocyte end-feet

Question 2

What are transport processes at the BBB?

Answer 2

• passive exchange via transcellular or paracellular diffusion
• uptake by facilitative or active carriers and receptor-mediated transport
• active efflux
• exchange by diffusion and bulk flow between brain interstitial fluid and CSF, which are not separated by a tight cellular barrier

Question 3

Give examples of in vivo methods for measurement of drug uptake in the brain

Answer 3

• whole tissue samples include vascular content, vasculature, brain cells and interstitial fluid
• microdialysis methods sample interstitial fluid
• catheters in ventricles or subarachnoid space collect CSF

Question 4

Give examples of in vitro methods for drug screening

Answer 4

• endothelial cell culture models (problem is the down regulation of BBB-specific transporters)
• conditionally immortalised cell lines
• in silico approaches (limitations are that the predictive capability is limited to passive, diffusional uptake since there are few molecular descriptors)

Question 5

Give examples of novel methods to temporarily open the BBB to allow drugs to reach their targets

Answer 5

• solution to draw out water from brain endothelial cells
• focussed ultrasound
• trojan horse method; attaching drugs to molecules naturally transported across the barrier

Question 6

What do neuroactive drugs act on?

Answer 6

• ion channels
• receptors
• enzymes
• transport proteins

Question 7

What can block voltage-gated ion channels?

Answer 7

some anaesthetics and anticonvulsants

Question 8

What causes an EPSP?

Answer 8

↑ Na+/Ca2+ influx or ↓ K+ efflux

Question 9

What causes an IPSP?

Answer 9

↑ Cl- and ↓ Ca2+ influx or ↑ K+ efflux

Question 10

What is an EPSP?

Answer 10

the change in membrane voltage of a postsynaptic cell following the influx of positively charged ions into a cell as a result of the activation of ligand-sensitive channel

Question 11

What does an EPSP result in?

Answer 11

depolarisation of the postsynaptic cell, thus increasing the likelihood of AP propagation

Question 12

What is an IPSP?

Answer 12

the influx of negative ions into, or the efflux of positive ions out of the postsynaptic cell

Question 13

What does an IPSP result in?

Answer 13

cell hyperpolarisation and thus decreases the likelihood of AP propagation

Question 14

How can presynaptic inhibition occur?

Answer 14

via a decreased Ca2+ influx elicited by activation of metabotropic receptors

Question 15

What are ionotropic ligand gated receptors?

Answer 15

directly linked to ion channels

Question 16

What are metabotropic ligand gated receptors?

Answer 16

indirectly linked by change in ion channel function via second messenger system

Question 17

What are possible mechanisms of CNS drug acting at synapses?

Answer 17

• presynaptically to alter the synthesis, storage, release, reuptake, or metabolism of transmitter chemicals
• pre-post synaptic receptors to activate or block

Question 18

Give examples of neurotransmitters and their function

Answer 18

• adrenaline - fight or flight
• noradrenaline - concentration
• dopamine - pleasure
• serotonin - mood
• GABA - calming
• acetylcholine - learning
• glutamate - memory
• endorphins - euphoria