ANS pharmacology Flashcards
NANCs
examples: NO 5 - HT (serotonin) GABA ATP neuropeptides (e.g. Y + VIP) purines
they allow for:
co transmission (simultaneously 2 or more NTs can be acting on target cell)
neuromodulation (individual nerve endings influence the behaviour of nearby nerve endings)
increasing cholinergic NT
2 ways:
cholinoceptor agonists
acetylcholineesterase inhibitors
decreasing cholinergic NT
cholinoceptor antagonists
cholinoceptor agonist: carbachol
terminal methyl group replaced by amino group.
agonist of both NAChR and MAChR
higher potency for NAChR
NAChR +++
MAChR ++
hydrolysed slowly by AChE as amino group blocks binding site at the enzyme
cholinoceptor agonist: methacholine
methyl group added to middle of the chain
agonist of MAChR and structural change has given produced a subtype specific agonist
is readily hydrolysed by AChE
cholinoceptor agonist: bethanecol
combination of changes in carbachol + methacholine
agonist of MAChR
is not hydrolysed by AChE and produces long lived muscarinic agonism
AChE activation
2 sites:
1. ser203 residue = esteric site which forms short lived ester bonds with ACh during its hydrolysis
- glutamate residue = anionic site
positively charged head group of ACh (carboxyl group) interacts ionicially with the negatively charged anionic site.
this interaction brings the hydroxyl group of the ACh molecule into close contact with the Ser203 residue @ the esteric site
the bond @ the ester site is destabilised and transferred onto the ser203 esteric site
the ACh molecule is hydrolysed and the ACh breakdown products diffuse out of the active site
AChE inhibition @ ser 203 residue by forming longer lived bonds
short, medium, long acting inhibitors
short acting AChE inhibitors
quaternary alcohol e.g. edrophonium
benzene group blocks esteric binding site
head group forms ionic bond.
short lived and readily reversible.
uses: myasthenia gravis diagnosis
medium acting AChE inhibitors
carbanyl esters e.g neostigmine and physostigmine
contain carbanyl group with is tranferred onto the esteric site and becomes gradually hydrolysed
long acting AChE inhibitors
pentavalent phosphorus compounds e.g. echotiopate + isofluorophate (dyflos)
consist of a labile group = fluorine atom or organic leaving group
labile group reacts very strongly with ser203 forming a stabile covalent bond
cause long term phosphorylation of ser203
uses: glaucoma treatment
reversing AChE inhibition
non enzymatic dephosphorylation agents (N - OH compounds)
e.g. pralidoxime
it removes the phosphate group formed on the ser203 residue and reactivates the enzyme
needs to be administered shortly after inhibition poisoning.
if there is long term inhibition poisoning it needs to be given with a muscarinic antagonist
dopamine NT
lacks enzyme Dopamine beta hydroxylase which would convert it to NA.
precursor of all catecholamines
L tyrosine
catecholamine formation pathway
L - tyrosine –> DOPA –> dopamine –> NA –> A
