PED1003/L16 Antidepressants

Question 1

Give 3 symptoms of depression.

Answer 1

Low mood
Hopelessness, despair
Guilt, suicidality
Anhedonia
Altered appetite

Question 2

What is the pathology of depression?

Answer 2

Unknown

Question 3

What does the pharmacology of effective antidepressant drugs suggest about the pathology of depression?

Answer 3

Dysnfunction of 5-HT and/or NA systems

Question 4

Give another name for serotonin.

Answer 4

5-HT

Question 5

What does the locus coeruleus contain? (3)

Answer 5

NAergic cell bodies
Projections to hypothalamus and midbrain
Projections to hippocampus and cortex

Question 6

What do the dorsal and median raphe nuclei contain? (2)

Answer 6

Serotonergic cell bodies
Projectioons to hypothalamus, hippocampus and cortex

Question 7

Describe the synthesis of noradrenaline (3).

Answer 7

Tyrosine -> L-DOPA
L-DOPA -> dopamine
Dopamine -> noradrenaline

Question 8

Name the 3 enzymes involved in noradrenaline synthesis.

Answer 8

Tyrosine hydroxylase
DOPA decarboxylase
Dopamine B-hydroxylase

Question 9

Describe 5-HT synthesis (2).

Answer 9

Tryptophan -> 5-HTP
5-HTP -> 5-HT

Question 10

Give the 2 enzymes involved in 5-HT synthesis.

Answer 10

Tryptophan hydroxylase
5-HTP decarboxylase

Question 11

How is NA/5-HT stored?

Answer 11

In vesicles (vesicular monoamine transporters - VMAT2)

Question 12

Where is monoamine oxidase present?

Answer 12

DA, NA and 5-HT terminals

Question 13

What breaks down transmitter in cytosol?

Answer 13

MAO

Question 14

What metabolises both NA and 5-HT?

Answer 14

MAO(A) and MAO(B)

Question 15

Describe NA metabolism (2)

Answer 15

NA -> DOPEG via MAO and aldehyde dehydrogenase
DOPEG -> MHPG via catechol-O-methyl transferase

Question 16

Describe 5-HT metabolism. (2)

Answer 16

5-HT -> aldehyde via MAO
Aldehyde -> 5-HIAA via aldehyde dehydrogenase

Question 17

Describe release and receptors of NA & 5-HT. (2)

Answer 17

Depolarisation causes exocytotic release
Receptors bind of pre- and postsynaptic membrane

Question 18

Give the 3 kinds of NA receptors.

Answer 18

A1
A2
B1, 2, 3

Question 19

What do A1 NA receptors do? (2)

Answer 19

Stimulate PI cycle
Increased DAG & [Ca2+]

Question 20

What do A2 NA receptors do? (2)

Answer 20

Inhibit adenylate cyclase, decreased cAMP
Open K+ channels (GIRK), hyperpolarise

Question 21

What do B1, 2, 3 NA receptors do?

Answer 21

Stimulate adenylate cyclase, increased cAMP

Question 22

Give 4 kinds of 5-HT receptor and their actions.

Answer 22

5-HT(A-F) inhibit adenylate cyclase, decreased cAMP
5-HT(1A) open K+ channel
5-HT(2(A-C)) stimulate PI cycle, increased DAG & [Ca2+]
5-HT(3) ligand-gated ion channel

Question 23

What kind of receptors are NA and 5-HT terminal autoreceptors?

Answer 23

NA - a2
5-HT - 5-HT(1B)
Both inhibitory

Question 24

How is NA/5-HT removed from the synaptic cleft?

Answer 24

Transporter proteins

Question 25

Give 2 1950's drugs found to elevate mood.

Answer 25

Iproniazid Imipramine

Question 26

What is the monoamine theory of depression?

Answer 26

Relative decrease in NA and/or 5-HT neurotransmission underlies the symptoms of depression

Question 27

What is the main target of current antidepressants? (2)

Answer 27

Presynaptic elements of NA/5-HT neurotransmission Inhibition of MAO or reuptake

Question 28

What are the issues with MAOIs? (2)

Answer 28

Increased DA transmission - stimulant Increased actions of sympathomimetic amines

Question 29

How do TCAs work?

Answer 29

Inhibit reuptake of 5-Ht and NA

Question 30

Give 3 side effects of TCAs.

Answer 30

H1 antagonism - sedation mACh antagonism - dry mouth A1 antagonism - postural hypotension

Question 31

Give 2 SSRIs/

Answer 31

Fluoxetine - Prozac Parxetine - Seroxat Sertraline - Zoloft Escitalopram - Cipralex

Question 32

How do SSRIs work?

Answer 32

Inhibit reuptake of 5-HT selectively and no receptor interactions

Question 33

Describe serotonin syndrome. (2)

Answer 33

MAOI plus reuptake inhibitor (TCA or SSRI) Synergistic increase in synaptic 5-HT provokes malignant hyperthermia

Question 34

Why don't antidepressant work acutely? (2)

Answer 34

Autoreceptor desensitisation Synaptic remodelling

Question 35

Describe acute desensitisation of autoreceptors. (5)

Answer 35

Reuptake blocked at cell body and terminal Autoreceptors activated Firing inhibited Terminal release inhibited Synaptic 5-HT levels are not increased

Question 36

Describe long-term desensitisation of autoreceptors. (4)

Answer 36

Autoreceptors desensitise Firing is restored Terminal release is restored Reuptake still blocked 5-HT levels in synaptic cleft elevated

Question 37

What does increased synaptic 5-HT do? (2)

Answer 37

Promotes synaptic remodelling Supports plasticity in forebrain neurones