Applied Neuropharmacology Flashcards
What are the steps in synaptic transmission?
- Synthesis and packaging of neurotransmitter (usually) in presynaptic terminals
- Na+ action potential invades terminal (action potential along axon)
- Activates voltage gated Ca2+-channels (flows in)
- 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 as its inactivated by enzymatic breakdown in synaptic cleft
What is the difference between ionotropic and metabotropic receptors?
Ionotropic receptors change shape when a neurotransmitter binds, creating a channel for molecules to travel through.
Metabotropic receptor activation result in the opening of channels somewhere else on the membrane
List eight ways drugs can reduce synaptic transmission
- Inhibit synthesis and packaging of neurotransmitter
- Activate presynaptic inhibitory receptors
- Block voltage gated Na+ channels
- Block post-synaptic receptors (i.e. non-comp/competitive antagonists)
- Block voltage-gated Ca2+ channels
- Increase breakdown of transmitter
- Block release machinery
- Increase uptake of transmitter
What is the effect of local anaesthetics?
Block voltage gated Na channels and therefore all action potentials (not too useful)
What is the effect of spider toxins?
Block the voltage gated Ca2+ channels and therefore block all transmitter release (not too useful)
What is the effect of botox?
Block the release machinery and therefore would block all transmitter release (not too useful)
List five ways drugs can increase synaptic transmission
- Increase synthesis and packaging of neurotransmitter (i.e. increasing availability of precursors)
- Activate post-synaptic receptors with an agonist
- Potentiate effect of transmitter on post-synaptic receptors (i.e. increase channel open time)
- Block breakdown of transmitter
- Block take of transmitter
What are the effects of allosteric drugs?
Activates the post-synaptic receptor, but potentiates the effects of the endogenous transmitter
I.e. benzodiazepines and barbiturates on GABA receptors
Give an example of a drug which blocks breakdown of transmitter
Anticholinesterases on ACh
Name six different types of neurotransmitters
- Acetylcholine
- Monoamines
- Amino acids
- Purines
- Neuropeptides
- NO
Give examples of monoamines
- Noradrenaline
- Dopamine
- Serotonin (5-HT)
Give examples of amino acids
- Glutamate
- GABA
- Glycine
Give examples of purine
- ATP
* Adenosine
Give examples of neuropeptides
- Endorphins
- CCK
- Substance P
What are the consequences of there bring a limited range of neurotransmitters?
A single neurotransmitter has multiple functions in different regions
Often in the brain and in the peripheral nervous system – separated by the blood brain barrier
What are the features of each neurotransmitter?
- Its own distribution
- Its own range of receptors it acts on
- It own range of functions in different regions (some separated by the blood brain barrier)
What are the different anatomical distribution of dopamine (DA) in the brain?
- Mesocortical pathway
- Nigrostriatal pathway
- Tubero-infundibular pathway
- Mesolimbic pathway
What is the mesocortical pathway?
Dopaminergic pathway which connects the ventral tegmental area (of midbrain) and the prefrontal cortex
What is the nigrostriatal pathway?
Dopaminergic pathway which connects the susbtantia nigra and corpus striatum (basal ganglia)