Applied Neuro-Pharmacology Flashcards
What is the sequence of evens in synaptic transmission?
- Synthesis and packaging of neurotransmitter (usually) in presynaptic terminals
- Na+ action potential invades terminal which 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
How can synaptic transmission be reduced by pharmacological manipulation?
- Block voltage gated Na channels
- Inhibit synthesis and packaging of NT
- Activate presynaptic inhibitory receptors
- Block postsynaptic receptors (eg. competitive antagonists, non competitive antagonists)
- Block voltage gated Ca channels
- Increase breakdown of transmitter
- Block release machinery
- Increase uptake of transmitter
- Block voltage gated Na channels
How can synaptic transmission be increased by pharmacological manipulation?
- Increase synthesis and packaging of NT (eg. by increasing availability of precursors)
- Activate postsynaptic receptors with an agonist
- Potentiate effects of transmitter on receptor (eg. increase channel open time)
- Block breakdown of transmitter
- Block uptake of transmitter
What types of neurotransmitters are there?
- Acetylcholine
- Monoamines
- Amino acids
- Purines
- Neuropeptides
- NO
Give examples of monoamine neurotransmitters
- Noradrenaline
- Dopamine
- Serotonin (5-HT)
Give examples of amino acid neurotransmitters
- Glutamate
- GABA
- Glycine
Give examples of purine neurotransmitters.
- ATP
- Adenosine
Give examples of neuropeptide neurotransmitters
- Endorphins
- CCK
- Substance P
Why is it no surprise that neurotransmitters have different functions in different regions?
There is a limited range of neurotransmitters
What does each neurotransmitter have?
- Its own anatomical distribution
- Its own range of receptors it acts on
- Its own range of functions in different regions (some separated by the blood brain barrier)
What is the anatomical distribution of dopamine in the brain?
- Brain stem
- Basal ganglia
- Limbic system an frontal cortex
What physiological functions are affected by dopamine?
- Vomiting
- Voluntary movement
- Emotions/reward
What is Parkinson’s caused by?
- Degeneration of DA cells in the substantia nigra (nigrostriatal)
- DA deficiency in the basal ganglia
How is dopamine synthesised?
- Glycine
- Alanine
- Phenylalanine
- Tyrosine
- DOPA
- Dopamine
Why can dopamine not evoke fast EPSPs or IPSPs?
No inotropic receptors
What are the names of the dopamine receptors?
5 subtypes of metabotropic (ie. g-protein coupled) receptors names D1-D5
How does the effect of dopamine differ through the brain?
It can produce many effects and different effects in different brain regions depending on the receptors expressed
What are the key enzymes in dopamine metabolic breakdown?
- MAO-B
- COMT
What does dopamine metabolic breakdown result in?
Homovanillic acid
How does Parkinson’s present?
Stiffness, slow movements, change in posture, tremor
What type of drugs can improve some symptoms of PD?
Dopaminergic drugs
What types of dopaminergic drugs are there?
- DA precursors
- DA agonists
Give an example of a DA precursor
Levodopa
Give examples of DA agonists ergots.
- Bromocriptine
- Pergolide
- Cabergoline
