Acetylcholine is an important neurotransmitter that acts on nicotinic and muscarinic receptors. It is synthesized from choline and acetyl-CoA, and is broken down by acetylcholinesterase. Acetylcholine plays a key role in muscle contraction and function of the parasympathetic nervous system. Inhibition of acetylcholinesterase by organophosphates or other toxins leads to excess acetylcholine activity and symptoms like muscle paralysis and respiratory failure.
2. Name : SOURABH TARAKESHWAR CHAUHAN
Class : S.Y.B Pharm
Roll No : 18
Division : A
Subject : Physical Pharmaceutics – Ⅱ
College : Shree D.D. Vispute College Of Pharmacy And Research Center, Gate No-04, Vichumbe,
New Panvel.
3. ACETYLCHO
LINE
Acetylcholine is secreted by neurons in many areas of the nervous
system but specifically by
(1) The terminals of the large pyramidal cells from the motor cortex
(2) Several different types of neurons in the basal ganglia
(3) The motor neurons that innervate the skeletal muscles
(4) The preganglionic neurons of the autonomic nervous system
(5) The postganglionic neurons of the parasympathetic nervous system
(6)Some of the postganglionic neurons of the sympathetic nervous
system
4. ACETYLCHO
LINE
• Acetylcholine (ACh) is the transmitter of the parasympathetic
autonomic nervous system and of the sympathetic ganglia
• Stimulation of the parasympathetic system produces effects that are
broadly opposite to those of the sympathetic system
• slowing of the heart rate
• Bronchoconstriction
• stimulation of intestinal smooth muscle
• ACh also acts at neuromuscular junctions
• ACh may be involved in learning and memory, as neurons containing
this transmitter also exist in the brain
5. Acetyl CoA + Choline
Acetylcholine
Acetate + Choline
choline acetyl
transferase Co A
Acetylcholine
esterase
synaptic cleft
Acetylcholine catabolism
Serine
Ethanolamine
CO2
Serine
decarboxylase
Choline
Glucose
SAM
Methionine
Vitamin B12
Homocysteine
6. ACH
RECEPTORS
• Two main classes of ACh receptors
1. Nicotinic
2. Muscarinic
Nicotinic receptors are ionotropic
• Bind nicotine
• Found on ganglia and at the neuromuscular junction
• Binding of Ach opens the channel for both Na+ and K+ to pass through
the membrane
• Action of the ligand on the channel is direct - so action is rapid
7. Muscarinic receptors, responding to the fungal toxin, muscarine, are
metabotropic
• More widespread in the brain than are nicotinic receptors
• The major receptors found on smooth muscle and glands innervated
by parasympathetic nerves
• Atropine specifically inhibits these receptors
8. • This process may propagate an action potential along a nerve fiber, or
it may lead to contraction of a muscle
• Acetylcholine is quickly destroyed by acetylcholinesterase in the
neuromuscular junction
• If, however, acetylcholine is not destroyed, as in the case of
inactivation of acetylcholinesterase, its continued presence causes
extended transmission of impulses
• In muscle fibers, continuous depolarization leads to paralysis
9. • The cause of death in DPF intoxication is respiratory failure due to
paralysis of the respiratory muscles (including the diaphragm and
abdominal muscles)
• Several organophosphorous compounds (malathion) are used as
agricultural insecticides, improper exposure to which can result in
toxic manifestations and death due to acetyl choline esterase
inactivation
• Pralidoxime has found use in the treatment of organophosphorous
poisoning and is most active in relieving the inhibition of skeletal
muscle acetylcholinesterase
10. • Contraction of the pupillary constrictor muscle causes miosis, a
reduction in pupil size
• Miosis is usually present in patients exposed to large systemic or
small topical doses of cholinomimetics, especially organophosphate
cholinesterase inhibitors
11. • Ciliary muscle contraction causes accommodation of focus for near
vision.
• Marked contraction of the ciliary muscle, often occurs with
cholinesterase inhibitor intoxication, is called cyclospasm
• Ciliary muscle contraction also puts tension on the trabecular
meshwork, opening its pores
• Facilitating outflow of the aqueous humor into the canal of Schlemm
• Increased outflow reduces intraocular pressure, a very useful result in
patients with glaucoma
• All of these effects are prevented or reversed by muscarinic blocking
drugs such as atropine
12. DURING
SURGERY……..
• Succinylcholine acts as competitive inhibitor of acetylcholine esterase
• Acetylcholine level increases
• Muscle paralysis – Muscle relaxation – required during surgery
• Acetyl choline stimulate intestinal function after surgery
