Dugga 3 - Cholinergic Flashcards
Which neurotransmitter does the cholinergic nervous system use?
Acetylcholine. Activates the motor nerves, peripheral nervous system and parasympathetic nerves for cardiac and smooth muscle
What are the two types of cholinergic receptors?
Muscarinic in smooth and cardiac muscle and nicotinic in skeletal muscle and in synapses between neurons
What is acetylcholine hydrolysed by?
Acetylcholinesterase when it departs the cholinergic receptor. The product choline is taken up and acetylated back to acetylcholine. Both cholinergic receptors and acetylcholinesterase are useful drug targets
Why can acetylcholine not be used as a drug?
It is hydrolysed rapidly by stomach acids and enzymes and shows no selectivity
What are cholinergic antagonists?
Binding to cholinergic receptors but not activating them
What do muscarinic antagonists usually contain?
Tertiary or quarternary nitrogen, functional group containing oxygen and branch point containing two hydrophobic ring substituents
What are nicotinic antagonists useful for?
Neuromuscular blockers in surgery
What is the pharmacophore of a nicotinic antagonist?
Two charged nitrogen atoms seperated by a spacer molecule to have a specific distance between them
What is the nicotinic receptor?
An ion channel consisting of five protein subunits
What is the muscarinic receptor like?
A G protein coupled receptor
What are anticholinesterases?
Inhibitors of the enzyme acetylcholineesterase
What is the active site of the acetylcholinesterase like?
A catalytic triad of amino acids histidine serine and glutamate
What is a carbamate inhibitor?
React with acetylcholineesterase to produce a stable carbamoyl bound intermediate which is slow to hydrolyse
What do organophospherous agents do?
Used as nerve gasses. Irreversibly phosphorylate serine in the active site
What is pralidoxime?
An antidote for organophosphate poisoning. Can bind to active site of phosphorylated enzyme and displace phosphate group from serine
