Applied Neuro-Pharmacology Flashcards
what is the sequence of events in synaptic transmission?
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
what are the pharmacological manipulation to reduce syncaptic transmission?
Block the voltage gated Na+ channels – eg local anaesthetics, would block all action potentials, not too useful.
Block the voltage gated Ca2+ channels – eg those clever spider toxins, would block all transmitter release, not too useful.
Block the release machinery, eg botox, would block all transmitter release, not too useful.
Block the postsynaptic receptors, eg receptor antagonists, competitive or non-competitive. Selectivity helps. Lots of examples of that.
Activate those presynaptic inhibitory receptors.
Increase breakdown of transmitter (though I can’t think of an example of that).
Increase uptake of transmitter (though I can’t think of an example of that).
Inhibit synthesis and packaging of transmitter.
what are the pharmacological manipulation to increase synaptic transmission?
Increase synthesis by flooding the cells with the appropriate precursors.
Use an agonist to activate the postsynaptic receptors - though that is not so useful because they get activated all the time – most of which is inappropriate.
Better to use an allosteric drug that does activate the receptor on its own, but potentiates the effects of the endogenous transmitter, eg benzodiazepines and barbiturates on GABA receptors.
Block break down of transmitter – eg anticholinesterases on Ach.
Or block the uptake of transmitter.
each neurotransmitter has…?
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 and frontal cortex
what are the physiological functions affected by dopamine?
Voluntary movement
Emotions / reward
Vomiting
what is parkinsons disease in regards to dopamine
Degeneration of DA cells in the SN (nigrostriatal)
DA deficiency in the basal ganglia
how many dopamine receptors are there?
5 subtypes of metabotropic (ie g-protein coupled) receptor named D1-D5
what do dopaminergic drugs improve?
Some motor features of Parkinson’s
e.g. limb rigidity & bradykinesia, tremor
what do dompaminergic drugs worsen or cause?
Nausea
Vomiting
Psychosis
Impulsivity / abnormal behaviours
what do dopaminergic antagonists improve?
Nausea
Vomiting
Psychosis
what do dopaminergic antagonists worsen?
parkinsons
what is the antagonist called that is a DA antagonist that doesnt cross the BBB
domperiodne
what is dyskinesias?
abnormal involuntary movements
are DA drugs or DA antagonist drugs more likely to cause dyskinesias?
DA drugs
