Drugs 3 - Catecholamines

Question 1

Noradrenaline cell bodies:

Answer 1

around 10,000 in the medulla and pons. mainly the locus coreleus but also solitary nucleus and lateral tegmental area

Question 2

Noradrenaline projections

Answer 2

LTA and SN to the spinal cord. locus coreleus to the amygdala, hypothalamus and thalamus cerebellum and cortex

Question 3

Noradrenaline transmission

Answer 3

almost paracrine from noradrenergic viscosities rather than nerve terminals. occur along the length of a population of neurons effecting all cells they pass.SYNAPSES EN PASSANT

Question 4

Noradrenaline reuptake

Answer 4

both synaptic degradation (MAO and COMT) and transporters (NET)

Question 5

Noradrenaline receptors

Answer 5

a1/2 b1/2/3

Question 6

Noradrenaline a1

Answer 6

cAMP (-)

Question 7

Noradrenalinea2

Answer 7

autorecptor IP3 (+)

Question 8

Noradrenaline B1

Answer 8

cAMP (+)

Question 9

Noradrenaline B2

Answer 9

cAMP (+)

Question 10

Noradrenaline B3

Answer 10

cAMP(+) periphery only

Question 11

functions of Noradrenaline receptors

Answer 11

autonomic function (HR, blood pressure and motor) and cognitive function (mood, fear, attention) TPJ = circuit breaker

Question 12

Drug targets:

Answer 12

–synthesis –reuptake (NET) –a2 –a/1b1/2/3 –MAO –vesicular packaging and release (reserpine)

Question 13

what is responsible for Noradrenaline vesicular packaging and release

Answer 13

reserpine

Question 14

what is NA synthesised from

Answer 14

tyrosine

Question 15

Dopamine is synthesised in

Answer 15

cells in the Substantia nigra and ventral tegmentum

Question 16

how do dopaminergic cells differ from adrenergic ones

Answer 16

they don’t contain phenylethanolamine N-methyltransferase

Question 17

dopaminergic pathways

Answer 17

meso limbic
meso cortical
nigrostriatal
tuberohypophoseal

Question 18

mesocortical pathway

Answer 18

from VTA to frontal lobe -the reward pathway. when we plan an action and its successful we reward ourselves with dopamine

Question 19

mesolimbic pathway

Answer 19

VTA to the amygdala and nucleus accumbens

Question 20

tuberophypophoseal

Answer 20

VTA to the pituitary, median eminence, hippocampus, hypothalamus - very short

Question 21

Nigrostriatal

Answer 21

SN to BG - movement, 75% of dopaminergic cells. 1 SN cell has 500,000 striatal synapses

Question 22

Dopamine functions

Answer 22

reward, movement, cognitive functions and modulation of other modulators (NA by locus coreleus and ACh) attention

Question 23

Dopamine modulation of ACh

Answer 23

Acts in the prabrachium presnaptically to increase ACh release (cog enhancement - attention and arousal)

Question 24

Dopamine receptors

Answer 24

Genreally post synaptic. D1 and D2 change levels of cAMP which acts with PKA to convert darpp to phospho darpp. phosphodarpp inhibits protein phophotase 1. PP1 strips other proteins and phosphotase enzymes to decrease activity.
This process is amplified so a little receptor inout has a big effect.
d1 and 2 generally found on different cells

Question 25

D1

Answer 25

excitatory. D1, D5. increase cAMP

Question 26

D2

Answer 26

inhibitiory, decrease cAMP, | d2,3,4

Question 27

Seratonin synthesised

Answer 27

from tryptophan (diet) in the raphe nuclei (medula and pons)

Question 28

serotonin projections

Answer 28

project back to spine medulla and cerebellum. Mainly forward to cortices and to hippocmapus, striatum, thalamus, hypothalamus, amygdala through same bundle as NA.

Question 29

serotonin metabolism

Answer 29

broken down by MAO to aldehydes then to v. soluble easily removable substrate by aldehyde dehydroxylase. No COMT involvement because its not a catecholamine

Question 30

serotonin receptors

Answer 30

all GPCRS except 5HTR-3. 1-7. Huge diversity is very good for drug targets.

Question 31

5HTR-1

Answer 31

presynaptic autoinhibitor

Question 32

5HTR-2

Answer 32

pre and post synaptic in cortex

Question 33

5HTR-3

Answer 33

ligand gated in cortex

Question 34

5HTR-4

Answer 34

limbic system and basal ganglia. also increases presynaptically increases ACh release so cog enhancement

Question 35

5HTR-5

Answer 35

No one knows!

Question 36

5HTR-6

Answer 36

hippocampus, cortex, limbic system

Question 37

5HTR-7

Answer 37

hippocampus, cortex, amygdala and thalamus - also GABA modulation

Question 38

Dopamine metabolism

Answer 38

MAO --> aldehyde | Aldehyde dehydroxylase + COMT --> HVA (verysoluble and easy to remove)

Question 39

serotonin dopamine and ach receptors also found

Answer 39

on the area postremma for vomiting