Neurotransmission and Drug Mechanisms (Yvonne Mbaki) Flashcards
Describe an electrical synapse
a.k.a gap junctions between cells
Each connexon has 6 connexcins in its structure - the connexon is the barrel shaped tunnel made up of 6 segements. Ions and small molecules are able to pass from one cell to another.
Describe chemical synapses
Acetylcholine, adrenaline etc are transported via chemical synapses. They are the main mode of communication.
- The NT is synthesised and packed into vesicles in the presynaptic nerve
- An action potential permits the fusion of the vesicle
- Exocytosis of the NT from the fused vesicle into the synaptic cleft
- NT binds to relevant receptors on the post synaptic membrane
- This initiates a signalling cascade downstream and cellular response
- Reuptake transporters on the presynaptic membrane take up excess NT
- Some NT in the cleft is terminated by enzymes into respective metabolites.
What is an excitation NT?
Glutamate causes downstream cascade as a result of Na+ depolarisation.
What is an inhibitory NT?
GABA is released from the presynpapse and causes hyperpolarisation in the post synaptic neurone as a result of Cl- inhibition.
Explain how ACh is released and recycled as a NT
AcetylCoA combines with choline to form Acetylcholine, this process is facillitated by choine-acetyltransferase. It is released by exocytosis from vesicles. In the synaptic cleft it is metabolised by acetylcholinesterase to acetate and choline. The choline can be recycled.
What kind of transmitters are GABA and glutamate?
Amino-acid transmitters
What are biogenic amines and how are they synthesised?
Dopamine, NA and Adrenaline are all biogenic amines. They are synthesised from tyrosine.
Tyrosine is converted to L-DOPA by tyrosine hydroxylase. L-DOPA becomes Dopamine via a DOPA decarboxylase. Dopamine is converted to noradrenaline via Dopamine beta-hydroxylase.
Noradrenaline to adrenalin is converted in the medulla and is facilitated by phenylethanolamine N-methyl-transferase.
What are Indolamines and how are they synthesised?
5H-T a.k.a serotonin
Synthesis starts with tryptophan, converted to 5 HTP (5-hydroxytryptophan) via tryptophan hydroxylase. 5 HTP is the converted to 5 HT by a 5-HTP decarboxylase.
Serotonin is terminated by MAO/COMT or reuptake.
What is MOA or COMT and its relevance to serotonin levels?
Enzymes that metabolise 5-HT in the synaptic cleft. Monoamine oxidase
Catechole-O-methyltransferase
Why is Nitric Acid described as an “atypical” neurotransmitter?
L-arginine is converted to NO It is not stored in vesicles Diffuses freely across cell membranes It is not released by exocytosis Termination is a passive process It is a retrograde messenger meaning that it doesn;t just move from pre to post synaptic membranes.
What is depleted in Parkinson’s disease? How can we treat this?
Dopamine is depleted/
We treat this by increasing levels of L-DOPA so that it can be converted into Dopamine
How can we treat anxiety and depression?
MAOi?
SSRi?
Effect the storage and release of serotonin.
By inhibiting MOA or COMT then we reduce the rate of metabolism of 5-HT (serotonin) from the synaptic cleft.
SSRi’s ihibit the reuptake of 5-HT therefore increasing its residency time at the synaptic cleft.
How do drugs of abuse affect the release of NTs? Namely MDMA and amphetamine.
MDMA (ecstasy) increases the release of serotonin, DA and NA.
Amphetamine causes non-exocytotic release of NA and DA
Both lead to an increase of NA that can increase heart rate and blood pressure.
How can we treat Alzheimer’s with an effect of neurotransmission termination?
Inhibition of acetylcholinesterase allows prolonged exposure of ACh in the synaptic cleft. This has minimal improvement on cognitive performance but does not stop progressive degeneration.
What drugs / receptors are targets in migraine?
Triptans - 5HT1 agonist
