Amines Flashcards
What are the 4 key amines involved in the CNS?
Noradrenaline, dopamine, 5-hydroxytryptamine and acetylcholine.
What are the features of amine systems in the CNS?
Cell bodies are restricted to a small number of brainstem nuclei and they lack specialised synaptic contacts.
What key roles do amines have in the CNS?
Arousal, attention, sleep and survival.
What is the name of an axon that contains amine neurotransmitters?
Aminergic axon.
What is the effect of amines when they bind to their receptors?
The change the response to the transmitter of an excitatory glutamate synapse. They are involved in neuromodulation.
What is noradrenaline involved in?
Arousal and emotional aspects of the brain - the “love” chemical.
Where do noradrenaline neurones originate?
The locus coeruleus.
Where do noradrenaline neurones project to?
It has diffuse innervation of the forebrain - in particular the cerebral cortex. They form a distinct neurotransmitter system.
What receptors does noradrenaline act at?
Alpha 1, beta1 and beta2 receptors. These are GPCRs.
What role does noradrenaline have in the brainstem?
Blood pressure control (baroreceptor reflex).
What role do descending noradrenaline pathways have?
Involvement in movement and pain.
What role does noradrenaline have in ascending pathways?
Arousal and mood, cognitive processes such as learning and memory, movement and attention.
What is depletion of noradrenaline in the forebrain involved in?
Depression.
What are the parts of the forebrain involved with noradrenaline?
The cortex and hippocampus.
What is overactivity of noradrenaline involved in?
Mania disorders such as bipolar.
What is the substrate for noradrenaline?
Tyrosine.
How is noradrenaline formed from its substrate?
Tyrosine is hydroxylated to L-DOPA by tryosine hydroxylase (TH) which then is decarboxylated by AADC (dopa decarboxylase) to dopamine and taken into vesicles by vesicular monoamine transporter (VMAT). Beta hydroxylation occurs within the vesicles.
What does dopamine-beta-hydroxylase do?
It converts dopamine to noradrenaline.
What neurones express dopamine-beta-hydroxylase?
Only noradrenaline neurones.
What is the limiting step of noradrenaline synthesis?
The hydroxylation to L-DOPA as the enzyme can become saturated, no matter how much tyrosine is present.
What can be produced by synthesis on demand in the noradrenaline production pathway?
Tyrosine hydroxylase and dopamine-beta-hydroxylase.
What happens if tyrosine hydroxlyase is blocked?
The pathway is stopped and no noradrenaline is produced, which can lead to depression.
What is reserpine?
A drug that prevents dopamine from being taken up and hydroxylated in the vesicles.
What can reserpine cause?
In rodents it has been shown to cause depressive symptoms.
What are the two ways in which noradrenaline can be inactivated?
It can be taken up into glial cells or taken up back into the presynaptic neurone.
What happens after noradrenaline has been reuptaken?
It is degraded by monoamine oxidase (MAO) and catecholo-methyltransferase (COMT).
What can MAO inhibitors be used for?
Depression.
What is overexpression of COMT linked to?
Schizophrenic phenotypes.
What else can be used to treat depression involving noradrenaline?
Uptake blockers.
What involvement does cocaine have on noradrenaline?
It blocks the uptake.
What does amphetamine do?
It displaces noradrenaline to cause stimulatory effects.
What is dopamine important for in the brain?
Reward mechanisms e.g. in wanting more chocolate.
What drugs of abuse release dopamine?
Alcohol, cocaine, amphetamine and cigarettes.
Where do dopamine neurones originate?
The substantia nigra and ventral tegmental area.
What receptors does dopamine act on?
D1-5 receptors (GPCR).
What part of the brain involved with dopamine controls movement?
The nigro-striatal area.
What part of the brain is involved with dopamine relating to attention , emotion and reward?
The mesocorticolimbic system.
How is dopamine synthesised?
The same as noradrenaline, but there is no dopamine-beta-hydroxylase in the vesicles, so only dopamine is released.
What is involved in the treatment of Parkinson’s disease?
L-DOPA, MAO inhibitors and COMT inhibitors.
How is dopamine involved in schizophrenia?
There is overactivity in the dopamine mesolimbic/cortical pathways.
How can schizophrenia be treated, in terms of dopamine?
Psychotropics can block DA receptors, however this can cause Parkinson’s like side effects. There is a hormonal imbalance via the TI pathway.
What is the other name for 5HT?
Serotonin.
Where do the neurones for 5HT originate in the brain?
Raphe nuclei.
What are the areas that forebrain projections go up to from 5HT neurones?
The dorsal and medium raphe areas.
What are the receptors for 5HT?
5HT1-7.
What is the key role of 5HT?
Mood - there is a dysfunction of serotonin in depression sufferers.
What else is serotonin involved in?
Sleep, appetite and sensory transmission.
What happens if there are large amounts of serotonin, in terms of sleep and hunger?
There is activation - insomnia and a loss of appetite and weight.
What is the substrate for 5HT?
Dietary tryptophan.
What is the synthesis process for 5HT?
It is taken up unto cell terminals by transporters and hydroxylated by tryptophan hydroxylase. It is then decarboxylated by 5HTP decarboxylase. It is then stored in vesicles.
How is 5HT inactivated?
It is inactivated by being reuptaken and the action of MAO.
Does the process have any rate limiters?
No - if there is more tryptophan there will be more production of serotonin as tryptophan hydroxylase is not saturated.
What is acetylcholine involved in?
Memory, amnesia arousal, sleep and walking.
Where do the neurones for acetylcholine originate?
Magnocellular neurones.
What receptors does acetylcholine act on?
Nicotinic (ionotropic) and muscarinic (GPCR).
What part of the brain (involved in acetylcholine) is involved in Alzheimer’s
Basal forebrain nuclei- there is degeneration.
What pathway of acetylcholine is involved in learning and memory?
The septo-hippocampal pathway.
What is the substrate for acetylcholine synthesis?
Dietary choline,
What is the process for synthesis of acetylcholine?
Choline is taken up into neurones and combines with acetyl coA, catalysed by choline acetyltransferase. Acetylcholine is then stored in vesicles.
Is the amount of choline rate limiting?
Yes - you can increase the synthesis of ACh by eating more.
How is ACh inactivated?
In the synaptic cleft by acetylcholine esterase.
What is formed when ACh is broken down?
Free choline and acetic acid. The choline is taken back into the axon.
