Applied Neuropharmacology Flashcards
(45 cards)
What is the sequence of events in synaptic transmission? What is the exception?
- Synthesis and packaging of neurotransmitter (usually) in presynaptic terminals
- Na+ action potential invades terminal
- Activates voltage gated Ca2+ channels
- Triggers Ca2+ dependent exocytosis of pre packaged vesicles of transmitter
- Transmitter diffuses across cleft and binds to ionotropic and/or metabotropic receptors to evoke postsynaptic response
- Presynaptic autoreceptors inhibit further transmitter release
- Transmitter is (usually) inactivated by uptake into glia or neurones
- Or transmitter is (unusually) inactivated by extracellular breakdown
- Transmitter is metabolised within cells
ACH IS THE EXCEPTION
How is Ach inactivated?
By enzymatic breakdown in the synaptic cleft
How are most transmitters inactivated?
By high affinity uptake into the neurons and glia
Examples of pharmacological manipulation to reduce synaptic transmission
Block the voltage gated Na+ channels e.g. local anaesthetics would block the APs
Block the voltage gated Ca2+ channels e.g. toxins from spiders
Block the release machinery e.g. botox - blocks all transmitter release
Block the post synaptic receptors e.g. receptor antagonists, competitive or non competitive
Activate those presynaptic inhibitor receptors
Increase breakdown of transmitter
Increase uptake of transmitter
Inhibit synthesis and packaging of transmitter
Examples of pharmacological manipulation to increase synaptic transmission
Increase synthesis by flooding the cells with the appropriate precursors
Use an agonist to activate the post synaptic receptors - not that useful cause activated all of the time
Allosteric drug which potentiates the effects of endogenous transmitters e.g. benzodiazepines and barbituates on GABA receptors
Block break down of transmitter e.g. Anticholinesterases on GABA
Block the uptake of transmitter
Examples of neurotransmitters
Acetylcholine Monoamines - noradrenaline - dopamine - serotonin (5-HT) Amino acids - Glutamate - GABA - Glycine Purines - ATP - adenosine Neuropeptides - endorphins - CCK - Substance P NO
What is the brain and the PNS separated by?
BBB
What does BBB stand for?
Blood brain barrier
What does each neurotransmitter have?
Anatomical distribution
Own range of receptors it acts on
Own range of functions in different regions (some seperated by BBB)
Exploited by therapeutic uses
Where is dopamine found in the brain?
Brain stem
Basal ganglia
Limbic system and frontal cortex
What physiological functions are affected by dopamine?
Vomiting
Voluntary movement
Emotions/rewards
Where is the vomiting centre found?
Brainstem
What is the function of the basal ganglia?
Regulates movement
What is involved in the limbic system?
Behaviour
Reward
Pathology of Parkinson’s disease
Degeneration of DA cells in the SN
DA deficiency in the basal ganglia
Fairly selective degeneration of a certain type of neurones
Does dopamine cross the BBB?
No
What are tyrosine and DOPA and can these get into the BBB?
Precursors of dopamine - these can get through the BBB
Where is DOPA broken down into dopamine?
In the liver
What are the dopamine receptors? What types of receptors are these?
D1 D2 D3 D4 D5 These are all metabotropic
Does dopamine have ionotropic receptors? What does this mean?
No
Dopamine cannot evoke fast EPSPs or IPSPs
What is the only neurodegenerative disorder that can be manipulated?
Parkinson’s disease
What TYPES of drugs can be used to treat parkinsons disease?
DA precursor
DA agonists
Enzyme inhibitors
Example of a DA precursor
Levodopa
Examples of DA agonists
Ergots - bromocriptine - pergolife - cabergoline Non-ergots - Ropinirole - Pramipexole - Rotigotine Apomorphine
