Monoamines

Question 1

What are monoamines? Examples?

Answer 1

The monoamines are a group of neurotransmitters that have extensive roles in the CNS and peripheral nervous system. The classic monoamines are:
* Adrenaline
* Noradrenaline
* Dopamine
* Serotonin
* Melatonin
Histamine
There is also trace amines and they are associated with TAAR’s and diet deprived.

Question 2

Briefly explain a typical monoamine synpase.

Answer 2

Nt’s are packed into vesicles, and released by mem pot change so they diffuse across to the post syn n. they cna they be recycled and reuptake for reuse.

Question 3

Key features of monoamines?

Answer 3

Long. diffuse projections
modulatory role on brain pathways’
Specific include dopamine in motor pathways/movement
Multiple r and subtypes
Good sites for drug therapy

Question 4

Key features about serotonin

Answer 4

discovered in LSSD misuse first CNS nt
involved in sleep, appetite, thermoreg, pain and mood
derived form dietary tryptophan
Also known as 5HT

Question 5

How is serotonin metabolised?

Answer 5

1. Hydroxylate tryptophan with the tryptophan hydroxylase 2 enzyme into 5-hydroxytrptophan.
   
   2. Remove carboxyl acid form the end. Using DOPA decarboxylase
   3. MOA enzymes and aldehyde dehydrogenase metabolism it into serotonin/5HT.

Question 6

What are the serotonergic pathways? here do they arise?

Answer 6

Arise in the Raphe nuclei and have large projections to the spinal cord.
cortex, hippo, BG, limbic system, hypothalamus
Cerebellum,medulla,sc.

Question 7

serotonin receptors

Answer 7

Expressed in CNS
use g protein modification
7 alpha subtypes currently 14 r identified
peripheral autonomic actions
pre and post locations
Family A GPCR
there 5HT 2a-c, 1b/d/e/f/a, 5a/b, 7,4,6,3

Question 8

Which receptors decrease cAMP/ increase cAMP, increase inositol phosphates and calcium/ LG cation channel?

Answer 8

-gi- 1a/b-f , 5a/b
-gs- 4,6,7
-gq- 2a-c
-LG cation channel- 3

Question 9

What are specific functions of different 5HT receptors?

Answer 9

1-anxiety, aggression, mood
2-addiction, anxiety, appetite, mood, vascon, resp
3- addiction, anxiety, learning memory, vomit
4- anxiety, gi mobility, learning/memory mood
5- sleep, locomotion
6-anxity, cognition, l/m, mood
7-anxiety, cognition, l/m, mood, res, themroreg, vascon

Have central and peripheral actions at pre and post locations

Question 10

Where is noradrenaline found?

Answer 10

cell bodies in the pons/medulla
10,000 an millions of synapses through the CNS

Question 11

What is the biosynthesis route of adrenaline?

Answer 11

tyrosine broken down by tyrosine hydroxylase into DOPA. DOPA broken down by DOPA decarboxylase into dopamine. Dopamine into noradrenaline using dopamine beta-hydroxylase. Noradrenaline into adrenaline using phenyl ethanolamine n-methyltransferase.

Question 12

What is the degradation of noradrenaline? What 2 main enzymes are involved?

Answer 12

1. Catechol-O-methyl transferase (COMT)
   
   • Add a methyl groupd, mostly degrates serotinin
     2. Monoamine oxidase (MAO)
   • Turn amine group into and aldehyde group
     Cause multiple potential products , and also is the same mechanism to degrade dopamine. Same effect.

Question 13

What structures are involved in the noradrenaline pathways?

Answer 13

locus coeruleus projects to
- solitary nucleus
- to spinal cord
- hypothalamus, neocortex, thalamus, temporal lobe.
cerebellum
also projects to adrenergic neurons and vasomotor/cardiovascular.

Question 14

Noradrenergic synapses?

Answer 14

Have swelling along the axon-have vesicles- they contain nt and have pre syn and have reuptake systems. Called variocositys
These syn are very wide- can cause leaking .
Lots of drug targets
* The rectors
* The breakdown by COMT
* Biosynthesis of nor adrenaline
* Reuptake
Can target all these processes
EMT is a transport is important in the periphery

Question 15

What are the different adrenoceptor subtypes?

Answer 15

a, a1, a1a, a1b, a2,a2a,a2b,a2c,a2d,b,b1,b2,b3
All Family A GPCR- same g protein signalling cascade

Question 16

What is dopamine?

Answer 16

-involved in PD, schizo, ADHD, drug abuse, endocrine disorders.
less widely distributed, diffuse into some pathways.
syn release
those cells lack b-hydroxylase so dopamine’s converted into NA.
-is a diffuse modulatory transmitter.
fast transmission big glu and gaba
projections from remote sparse nuclei
synpases to SN, Straitum.

Question 17

Dopamine degradation

Answer 17

COMT enzymes are involved and MAO . COMT breaks dopamine into 3-MT then MAO turns 3MT into HVA. MAO breaks dopamine into DOPAC and then COMT breaks DOPAC into HVA.

Question 18

What are 4 pathways involved in the dopamine pathway? What brain areas are involved in these pathways?

Answer 18

• mesocortical
  -nigrostriatal
  -tuberos-infundibular
  -mesolimbic
  dorsal striatum, thalamus, putamen, hypothalamus, nucleus accumbens, cerebellum, substantia nigra, ventral tegmental area, pituitary.

Question 19

What type of receptors are dopamine and what types are there?

Answer 19

Family A GPCR
d1-d1/d5- Gs CAMP
d2-d2/3/4- Gi CAMP

Question 20

How does dopamine and CAMP work?

Answer 20

DARPP32 converted to DARPP32 PI as cAMP converted into PKA. can also be reversed back with calcineurin. DARPP32 PI turns into protein phosphatase 1 as a p+ pi back to protein.