Neuropharmacology Flashcards
what is the sequence of events in synaptic transmission?
synthesis and packaging of the neurotransmitter in presynaptic terminals, Na+ action potential invades terminal and activates voltage gated Ca2+ dependent exocytosis of pre-packaged vesicles of transmitter, transmitter diffuses across cleft and binds to ionotopic and/or metabotropic receptors to evoke postsynaptic response, presynaptic autoreceptors inhibit further transmitter release, transmitter is inactivated by uptake into glia or neurones or transmitter is inactivated by extracellular breakdown and transmitter is metabolised within cells
why is it no surprise that a single neurotransmitter has multiple functions in different regions and what does this mean?
as there is a limited range of neurotransmitters so when you manipulate a single neurotransmitter you are probably going to manipulate multiple functions
what are the different types of neurotransmitter?
acetylcholine, monoamines (NA, dopamine, serotonin), amino acids (glutamate= excitatory, GABA and glycine= inhibitory), purines (ATP and adenosine) and neuropeptides (endorphins, CCK, substance P) and NO
what is the anatomical distribution of dopamine in the brain?
brainstem, basal ganglia, limbic system and frontal cortex
what physiological functions are affected by dopamine?
voluntary movement, emotions/reward and vomiting
describe the pathway of dopamine synthesis.
glycine, alanine, phenylalanine, tyrosine, DOPA, dopamine
why can we not give tyrosine to modulate DA in vivo?
dopamine cannot cross the BBB but tyrosine and DOPA can, tyrosine hyrdoxlyase is lost through degeneration so cannot give tyrosine as will not be converted to DOPA and so dopamine
what do we usually give then to modulate DA in vivo?
DOPA as it can be converted to dopamine
what is a problem of DOPA and how do we fix this?
DOPA can however be converted to dopamine in the periphery which can lead to unwanted side effects to due excess dopamine in the periphery leading to vomiting and hypotension so can be pharmacologically blocked to prevent this and more of the DOPA administered will cross the BBB
describe the dopamine receptors.
dopamine acts on dopamine receptors at the post-synaptic membrane, there are 5 subtypes of metabotropic (ie g-protein coupled) receptors names D1-D5 so dopamine can produce many effects and different brain regions so depending on which receptors are expressed so in theory at least a selective agonist or antagonist could produce a specific therapeutically useful effect
what are the possible DA precursor drugs?
levodopa which is converted into dopamine in the brain
what are the possible DA agonist drugs?
non-ergots= ropinirole, pramipexole, rotigotine and apomorphine which act on the dopamine receptors
what drugs are used to inhibit peripheral AAAD enzymes?
carbidopa and benserazide which reduce the peripheral side-effects of levodopa and allows a greater dose to reach the CNS
what are the MAOB inhibitors?
selegiline, rasagiline, safinamide
what are the COMT inhibitors?
entacapone and opicapone
