Neuropharmacology IGNORE

Question 1

Aripiprazol

Answer 1

Antipsychotic (atypical), D2 partial agonist, 5-HT1A partial agonist

Question 2

Why is developing CNS drugs very difficult?

Answer 2

Aetiology of most CNS disorders is not well understood
Side effects of CNS active compounds are often unacceptable
Compounds must be able to cross the BBB

Question 3

Describe the blood brain barrier

Answer 3

Thick basement membrane on which endothelial cells are linked together by tight junctions, preventing the free movement of substances out of the capillaries
Surrounded by astrocytic endfeet, further preventing drug penetration

Question 4

How can drugs cross the BBB?

Answer 4

Non-polar
Amphipathic (hydrophobic or hydrophilic groups)
Transported by membrane transporters

Question 5

Levodopa/L-DOPA

Answer 5

Substrate for DOPA decarboxylase
Used to treat Parkinson’s
Transported by BBB neural amino-acid transporter (unlike DA)

Question 6

Domperidone

Answer 6

Antiemetic
D2/3 receptor antagonist
Used to limit levodopa-induced nausea
Peripherally restricted as pumped out across the BBB by multidrug resistance transporters (MDR1/p-glycoprotein)

Question 7

In which conditions can the BBB become leaky?

Answer 7

Trauma, epilepsy, migraine

Question 8

Which brain regions don’t have a BBB? Why?

Answer 8

Area postrema and circumventricular organs

Usually involved in sampling of humoral content/hormonal release/border ventricular system

Question 9

How many CNS neurons?

Answer 9

10^11

Question 10

Subtypes of glial cell?

Answer 10

NB More glial cells than neurons

1. Astrocytes - maintain extracellular environment around neurons and synapses via reuptake systems. Also synthesise NTs.
2. Oligodendrocytes - form myelin sheaths around axons
3. Microglia - mphage like, provide immune defence activated by brain injury and disease pathology.

Question 11

Name the 4 main parts of the neuron and their function

Answer 11

1. Cell body - synthesises and processes proteins
2. Dendrites - receive information
3. Axon - enables transmission of AP from one neuron to another
4. Presynaptic terminals - release molecules that diffuse across the synaptic cleft to the postsynaptic cell.

Question 12

What are the physical types of synapse?

Answer 12

1. Axodendritic
2. Axosecretory (blood vessels)
3. Axoextrafcellular
4. Axosomatic
5. Axosynaptic (other presynaptic synapses)
6. Axoaxonic

Question 13

Glutamate
Type
Action
Receptor

Answer 13

Amino acid
Fast excitatory 
Ionotropic: AMPA/Kainate/NMDA
GPCR:
mGluR

Question 14

GABA
Type
Action
Receptor

Answer 14

Amino acid
Fast inhibitory
Ionotropic GABA A/C
GPCR GABAB

Question 15

Glycine
Type
Action
Receptor

Answer 15

Amino acid
Fast inhibitory
Ionotropic Glycine receptor

Question 16

Dopamine
Type
Action
Receptor

Answer 16

Catecholamine
Modulatory
GPCR D1-5

Question 17

NA
Type
Action
Receptor

Answer 17

Catecholamine
Modulatory
GPCR alpha12 beta123

Question 18

5-HT
Type
Action
Receptor

Answer 18

Indolamine
Modulatory
GPCR 5-HT1247
Ionotropic 5-HT3

Question 19

Acetylcholine
Type
Action
Receptor

Answer 19

x
Modulatory
GPCR Muscarinic
Ionotropic Nicotinic

Question 20

Histamine
Type
Action
Receptor

Answer 20

x
Modulatory
GPCR
H1-3

Question 21

Name the neuropeptides
Type
Action
Receptor

Answer 21

Substance P, neuropeptide Y, endorphins, CTRH
GPCR
Neuromodulation

Question 22

Lipid mediators
Type
Action
Receptor

Answer 22

Prostaglandins, endocannabinoids, GPCR

Neuromodulation

Question 23

Gaseous
Type
Action
Receptor

Answer 23

NO CO
GC
Neuromodulation

Question 24

Neurotrophins, cytokines
Type
Action
Receptor

Answer 24

NGF, brain-derived neurotrophic factor, IL-1
Kinase-linked receptors
Neuronal growth, survival and functional plasticity

Question 25

Steroids
Type
Action
Receptor

Answer 25

Androgens, oestrogens
Nuclear and membrane receptors
Functional plasticity

Question 26

What is the difference between neurotransmission and neuromodulation?

Answer 26

Transmission = fast = ligand-gated ion channel
Modulation = slower GPCR, or GC

Question 27

Define metabotropic

Answer 27

GPCR

Question 28

Define ionotropic

Answer 28

Ligand-gated ion channel

Question 29

Define volume transmission

Answer 29

NT release from varicosities

Diffusion of NT a wider area involves non-synaptic localisation of receptors

Question 30

Define retrograde transmission

Answer 30

NTs may diffuse back to the presynaptic terminal to activate receptors

Question 31

Define paracrine transmission

Answer 31

NTs diffuse back away from the synapse to activate nearby cells

Question 32

How do you modulate synaptic communication?

Answer 32

1. Inhibit NaV
2. Reduce or enhance NT production in the terminal
3. Inhibit presynaptic vesicular transport
4. Displace transmitter from vesicles
5. Inhibit KvS to lengthen AP and cause more release of NT
6. Alter CaV to change the amount of vesicle exocytosis
7. Block vesicle release machinery
8. Agonists and antagonists
9. Add or remove receptors
10. Modulate receptors (ie phosphorylation)
11. Change receptor subunits
12. Inhibit presynaptic transmitter re-uptake
13. Alter breakdown of transmitters in presynaptic terminal of synaptic cleft

Question 33

How do you synthesise glutamate?

Answer 33

GABA + alpha-oxoglutarate = glutamate + succinic aldehyde.