Autonomic Neurotransmission & drugs affecting it II ANS Pharmacology II Nervous System Physiology II This video will be about : 1. Cholinergic Neurotransmission- acetylcholine synthesis, its release and removal from synapse 2. Drugs affecting the cholinergic neurotransmission 3. Adrenergic neurotransmission- norepinephrine synthesis, its release and removal from synapse 4. Drugs affecting the adrenergic neurotransmission 5. Epinephrine synthesis You can also watch the same topic on HM Learnings Youtube channel. You can also follow HM Learnings on facebook, instagram and twitter for daily updates

2. Acetylcholine- Synthesis, release, removal
• Ach is present in small, clear synaptic vesicles in the cholinergic nerve
endings.
• It is synthesized in the cholinergic nerve endings .
• Choline is taken from the extracellular space via Na+ dependent choline
transporter located on the presynaptic nerve membrane.
• Choline combines with acetyl-CoA in the presence of choline
acetyltransferase to form Ach.
• Ach is then transported inside the synaptic vesicles via the vesicle-
associated transporter along with peptides and ATP.

4. Release of Ach- Exocytosis
• Ach is released from the presynaptic neuron into the synapse in
response to AP.
• The AP causes the change in membrane potential of presynaptic
membrane and leads to the opening of voltage gated Ca2+ channel
• Ca2+ influx will cause the movement of synaptic vesicles towards the
synapse
• Fusion of presynaptic membrane and vesicular membrane will release
Ach in the synaptic cleft.

5. Removal of Ach
• Ach will bind to the cholinergic receptor located on the post-synaptic
membrane.
• It will be then removed from the synapse by the following ways:
1. Enzymatic degradation- Acetylcholinesterase is located at the post-
synaptic membrane. It will degrade Ach into acetate and choline.
2. Diffusion from the synaptic cleft into surroundings.

7. Drugs affecting cholinergic neurotransmission
Transmission
process
Site of Drug action Drug involved Drug action Uses
Neurotransmitter
synthesis
Na+ dependent
choline transporter
on presynaptic
membrane
Hemicholinium Blocks choline
uptake
Experimental
studies
Neurotransmitter
storage
Vesicle associated
transporter on
vesicle membrane
Vesamicol Prevents intake of
Ach into vesicles
for storage
Experimental
studies
Neurotransmitter
release
Cleaves SNAP,
synpatobrevin
Botulinum toxin Inhibits docking Controls muscle
spasms
Neurotransmitter
inactivation
Acetyl
cholinesterase
Neostigmine,
Physostigmine,
organophosphates
Inhibition of
enzyme, prolongs
the action of Ach
Myasthenia gravis,
glaucoma

8. Norepinephrine- Synthesis, release, removal
• NE is present in small, dense synaptic vesicles in the adrenergic nerve
endings.
• It is synthesized in the adrenergic nerve endings.
• Tyrosine is taken from the extracellular space via Na+ dependent
tyrosine transporter located on the presynaptic nerve membrane.
• Tyrosine
• It is the rate limiting step. TH can be inhibited feedback by dopamine
or NE
• DOPA
DOPA (Dihydroxy-phenylalanine)
Tyrosine hydroxylase
DOPA decarboxylase
Dopamine

9. • Dopamine enters inside the vesicle through the vesicular monoamine
transporter (VMAT).
• Inside the vesicle, Dopamine
• Norepinephrine is the only small-molecule transmitter that is
synthesized in synaptic vesicles instead of being transported into the
vesicle after its synthesis.
• In CNS and adrenal medullary cells, NE leaves the vesicles
• Norepinephrine
• Epinephrine enters the vesicles and stored till the next impulse.
Dopamine beta
hydroxylase
Norepinephrine
Phenylethanolamine
N – methyltansferase
Epinephrine

11. Release of NE
• NE is released from the presynaptic neuron into the synapse in
response to AP.
• The AP causes the change in membrane potential of presynaptic
membrane and leads to the opening of voltage gated Ca2+ channel
• Ca2+ influx will cause the movement of synaptic vesicles towards the
synapse
• Fusion of presynaptic membrane and vesicular membrane will release
NE in the synaptic cleft.

12. Removal of NE
• NE will bind to adrenergic receptors located on the post-synaptic
membrane.
• Then, it will be removed from the synapse in the following ways-
1. Reuptake by norepinephrine transporter (NET) into the presynaptic
neuron.
2. Diffusion from the synaptic cleft into the surrounding.
3. Enzymatic degradation by monoamine oxidase and catechol-N methyl
transferase.

14. Drugs affecting adrenergic neurotransmission
Transmission
process
Site of Drug action Drug involved Drug action Uses
Neurotransmitter
synthesis
cytoplasm of nor-
adrenergic endings
Metryosine Blocks tyrosine
hydroxylase
Pheochromocyto
ma (adrenal
medulla tumor)
Neurotransmitter
storage
Vesicle associated
transporter on
vesicle membrane
Reserpine Prevents intake of
NE into vesicles
for storage
Hypertension
Neurotransmitter
release
Bretylium,
guanethidine
Hypertension,
chronic pain
Neurotransmitter
reuptake
Norepinephrine
transporter
Cocaine, tricyclic
antidepressants
Inhibition of
uptake and
prolongs the
action of Ach
Depression

15. Upcoming video
• Diseases of Autonomic Nervous System