Biogenic Amines Flashcards
(47 cards)
Give example of an indolamine
Serotonin
Give examples of catecholamines
Dopamine
Noradrenaline
Adrenaline
Give example of an imidazoleamine
Histamine
How is dopamine synthesised ?
Tyrosine to L-dihydroxyphenylalanine by tyrosine hydroxylase
L-dihydroxyphenylalanine to dopamine by dopa decarboxylase
Is tyrosine an essential or non essential amino acid ?
Non essential but we still take it in in our diet so there’s a plentiful supply of it
What does alpha- methyl-p-tyrosine do ?
Inhibits tyrosine hydroxylase
It’s used as a research tool but not clinically because if it is given clinically then you wouldn’t be able to produce any of the catecholamines
What is the rate limiting step in dopamine synthesis ?
Tyrosine hydroxylase
L-dopa can be given to bypass this rate limiting step
What drug if administered alongside l-dopa in the treatment of PD and why ?
Carbidopa
Because L-dopa can be converted to dopamine in the periphery but we want it in the brain and dopamine can’t cross the BBB but L-dopa can so the carbidopa blocks periphery dopa decarboxylase
Where is dopamine within neurons ?
Some is stored in ready releasable pools - use VMAT transporter to put dopamine into vesicles
Some is just present in the cytosol
Some is in long term storage - in vesicles just further back from the active zone
What happens to dopamine once it’s released ?
1- some binds to pre and post synaptic receptors
2- some diffuses away from the cleft
3- some is taken back up into the terminal by a specific dopamine transporter
What are the dopamine receptors ?
Metabotropic
D1-D5
2 families : D1 like (1 and 5) and D2 like (2,3 and 4)
How do D1 like receptors work ?
Linked to Gs Activate adenylate Cyclase Increase cAMP Increase pKA Proton phosphorylation Eg inhibits GIRK to cause depolarisation
How do D2 like receptors work ?
Linked to Gi
Inhibit adenylate Cyclase
Decrease cAMP
Decrease pKA and protein phosphorylation
EF cause opening of potassium channels causing inhibition
These are the most important ones for drug therapy but most drugs are not selective
How is dopamine reuptaken ?
Taken up by specialised transporter - reducing its effects
It is a probable site for drug action
What do amphetamines do ?
Block uptake transporter and increase levels of dopamine in the synaptic cleft
Also reverses the transporter to increase the release of dopamine from the cytosol
How does cocaine work ?
Blocks dopamine up take transporter so enhances dopamines effects
What are 2 examples of therapeutic dopaminergic drugs ?
Benzhexol and amantadine
What is cocaine ?
Alkaloid found in leaves of South America shrub erthroxylon coca
Powerful psychostimulant
Acts of dopaminergic pathways involved in reward
Primarily blocks reuptake in the midbrain causing exhilaration
What are amphetamines ?
Synthetic compound
Psychomotor stimulant
Many sympathomimetic effects
Inhibits uptake of catecholamines and inhibits mono amine oxidase so stops them being broken down
What are the 2 pathways involved in dopamine catabolism ?
Monoamine oxidase - 90%
Catechol-o-methyltransferase -10%
Describe the MAO catabolism pathway for dopamine.
Dopamine to 3,4-dihyroxyphenylacetylaldehyde by MAO
3,4-dihydroxyphenylacetylaldehyde to 3,4-dihydroxyphenylacetic acid by aldehyde dehydrogenase
3,4-dihydroxyphenylacetic acid to homovanilic acid by COMT
Describe the COMT pathway to catabolise dopamine
Dopamine to 3-methoxytyramine by COMT
3-methoxytyramine to 3-methoxy-4-hydroxy-phenylacetylaldehyde by MAO
3-methoxy-4-hydroxyphenylaldehyde to homovanilic acid by aldehyde dehydrogenase
Where is MAO found ?
In membrane of mitochondria
2 types a and b
Dopamine metabolised by both
What happens to dopac and hva ?
Dopac can be eliminated directly whereas hva is eliminated in the CSF
