exam 1 lecture 4 cholinesterase inhibitors Flashcards
AChE
highly selective for ACh
positive charge of amine binds anionic site
oxygen binds to OH on serine of esteratic site
hydrolyzes ACh so that choline can be used to create more ACh
plasma cholinesterase
selective for ACh + succinylcholine
tetra-alkylammonium ion (qauternary amine)
blocks binding to anionic site + block ACh binding
noncovalent –> reversible binding
(no ester)
quaternary amine alcohol
blocks binding to anionic site + blocks ACh binding
noncovalent (no ester) –> reversible binding
carbamate
quaternary or tertiary ammonium groups
forms covalent bond –> more slowly hydrolyzed than ACh, but still reversible
neostigmine + pyridostigmine
endrophonium
pyridostigmine
neostigmine
prevents myasthenia gravis (skeletal muscle weakness due to loss of nicotine receptor) by AChE inhibition
physostigmine
can cross BBB due to lack of charge
antidote to antimuscarinic poisoning
antagonizes CNS (m1 R)
organophosphate
strong covalent binding to serine 203
irreversible
used for glaucoma
echothiophate
used to treat glaucoma
increase ACh + muscarinic receptor activity
increase M3 activity to contract ciliary muscle to increase outflow of aqueous humor
caution: too much cholinergic receptor activity
malathion + dizainon
insecticides
carboxyesterase in mammals hydrolyzes to form inactive compound
pralidoxime
strong nucleophile that can hydrolyze organophosphate if used before aging
+ charge –> cannot cross BBB
combine with atropine
atropine
blocks access to muscarinic receptors
can’t block action of nicotinic receptor
alzheimers
dementia due to loss of cholinergic receptors
ache inhibitors can be used to increase cholinergic activity
donepezil
binds anionic to block ACh binding to AChe
reversible, noncovalent
treatment of symptoms by increasing cholinergic activity
rivastigmine
reversible AChE inhibitor
carbamate
longer acting
