Lecture 7 (Drugs Targeting Nicotinic & Muscarinic Receptors) Flashcards
For the sympathetic system the preganglionic neurotransmitter is ___
Ach
For the sympathetic system the preganglionic receptors are ?
nicotinic ganglionic (NG)
For the sympathetic system the post ganglionic is ___
NA or NE (same chemical)
For the sympathetic system the post ganglionic receptors are ?
Adrenergic
alpha 1, beta 1, beta 2
For the parasympathetic system the preganglionic neurotransmitter is ___
Ach
For the parasympathetic system the preganglionic receptors are ?
nicotinic ganglionic (NG)
For the parasympathetic system the postganglionic neurotransmitter is ___
Ach
For the parasympathetic system the postganglionic receptors are ?
Muscarinic (M)
The somatic nervous system is ____ controlled.
consciously
Neurotransmitter for somatic nervous system is ?
ACh
Receptors for somatic nervous system are ?
nicotinic cholinergic (NM)
Explain the synapse for ACh
- action potential
- this opens calcium channels which acts as a stimulus for Ach to leave presynaptic cell and go into the synaptic cleft
- Ach then attaches to Ach receptors on post synaptic cell
- while in presynaptic cleft, Ach can be broken down by AChE into acetate + choline
- choline can be reuptaked into the presynaptic cell and added to AcCoA to make Ach
*see slide 6 for diagram
ACh has what two groups on it?
ester
amine
AChE ____ Ach
hydrolyzes
(it chops the ester bond
When AChE hydrolyzes Ach, what are the two products?
acetic acid and choline
All cholinergic receptors bind ___ for activity
ACh
two types of cholinergic receptors?
nicotinic
muscarinic
What two types of nicotinic receptors are there?
NG - nicotinic ganglionic
NM - nicotinic cholinergic
How many types of muscarinic receptors are there?
5
M1-M5
All muscarinic receptors are _____
GPCRs
Nicotinic acetylcholine receptors us a ___ ion channel
sodium (Na+)
How does the nicotinic acetylcholine receptor work?
Ach binds to ion channel which opens the ion channel and allows Na+ to pass through
2 examples of NM agonists
succinylcholine
decamethonium
2 examples of NM antagonists
pancuronium
d-tubocurarine
Although succinylcholine and pancuronium work via different mechanisms, they are used clinically for the same thing: which is?
muscle relaxation during surgery
Succinylcholine is rapidly hydrolyzed by _____
esterases
Pancuronium has a ____ duration of action than succinylcholine
longer
2 examples of NG selective antagonists
trimetaphan
hexamethonium
M1 receptor affects G alpha __
q
M2 receptor affects G alpha __
i
M3 receptor affects G alpha __
q
M1 = _____
excitation
+PLC
increase IP3 and DAG
increase [Ca2+] intracellular
decrease K+ outflow
M2 = _____
inhibition
-AC
decrease cAMP
decrease [Ca2+] intracellular
increase K+ outflow
M3 = ______
excitation
+PLC
increase IP3 and DAG
increase [Ca2+] intracellular
decrease K+ outflow
M1 reaches which tissue locations?
CNA (cortex hippocampus)
ganglia
parietal cells
M2 reaches which tissue locations?
cardiac - atria and conducting tissue
neural - presynaptic terminals
M3 reaches which tissue locations?
smooth muscle
vascular
endothelium
M1 function
CNS excitation (memory)
gastric acid secretion
GI motility
M2 function
cardiac inhibition decrease HR decrease force of contractility presynaptic inhibition neural inhibition
M3 function
smooth muscle contraction (bladder)
What does removing methyl groups on Ach do?
reduces potency
On ACh what is required for activity
N+
is the ACh molecule flexible?
yes
Receptors for ACh have 2 sites - what are they?
anionic site (can accommodate two methyl groups and has a - change binding site) esteratic site (ester O acts as H bond acceptor)
For muscarinic agonists, as the length of the alkyl chain increases beyond _ atoms, intrinsic activity and affinity decrease
5
> _ atoms usually have no activity or affinity (muscarinic agonists)
7
Carbonyl on ACh is a strong __________
electrophile
ACh is very susceptible to _______
hydrolysis
What does adding a methyl group to ACh do? (it is now methacholine)
methyl group = steric shield
-reduces access to carbonyl carbon by nucleophiles also sterically inhibits binding to AChE
_______ has delocalized electrons on the acetyl group which decreases the electrophilic nature of the carbonyl carbon - makes it resistant to hydrolysis by AChE
carbachol
_____ and _____ are not orally active and not useful clinically
ACh
Carbachol
What is ethacholine used for?
- used as a test for asthma
- called the methacholine challenge test
What is Bethanechol used for?
- increase urinary output
- used often after surgery
- or used in prostatic hypertrophy that does not respond to convention treatments like Tamsulosin
What is Pilocarpine used for?
treats glaucoma
