4. Cholinergic Receptors(Cholinoceptors)-
Types & Characteristics
Acetylcholine Receptors (Cholinoceptors)
Main subdivision is into muscarinic
(mAChR) and nicotinic (nAChR) subtypes
In smooth muscle, cardiac muscle and
glands the cholinergic receptors are of the
muscarinic (mAChR) type (i.e. stimulated
by muscarine, an alkaloid from Amanita
muscaria mushrooms)
5. Cholinergic Receptors(Cholinoceptors)-
Types & Characteristics
Acetylcholine Receptors (Cholinoceptors)
In striated (skeletal) muscle and autonomic
ganglia (sympathetic and parasympathetic)
the cholinergic receptors are nicotinic (nAChR)
(i.e. stimulated by nicotine)
mAChR’s are G-protein coupled receptors,
causing:
Activation of phospholipase C
Inhibition of adenylate cyclase
Activation of potassium channels
Inhibition of calcium channels
6. Cholinergic Receptors(Cholinoceptors)-
Types & Characteristics
Muscarinic Acetylcholine
Receptors(mAChR’s)
Five types occur, viz.:
M1-receptors (neural)- Selectively blocked by
pirenzepine
M2-receptors (cardiac)- Decrease cardiac
contractility and heart rate; selectively blocked by
gallamine
M3-receptors (glandular)- causing secretion, visceral
smooth muscle contraction, vascular relaxation
M4-receptors & M5-receptors- largely confined to
CNS; functional role not well understood
7. Autonomic Nervous System(ANS)-
Cholinergic Receptors
M1-receptors -
M1, M3 and M5
receptor subtypes
have stimulatory
effect on the target
tissue
M2 and M4 subtypes
are inhibitory
9. Cholinergic Receptors(Cholinoceptors)-
Types & Characteristics
Nicotinic Acetylcholine Receptors(nAChR’s)
Two types occur, viz.:
NM receptors (muscle type)- located at
skeletal muscle neuromuscular junction,
Na+, K+ depolarizing ion channel, blocked by
d-tubocurarine
NG receptors (neuronal type)- located at
postganglionic cell body, Na+, K+
depolarizing ion channel, blocked by
hexamethonium
10. Cholinergic (Cholinoceptor Activating)
Drugs
Cholinergic Drugs(Cholinomimetics/
Parasympathomimetics)
Drugs producing actions similar to that of
Acetylcholine (ACh)
Two modes of action:
May directly interact with cholinergic
receptors
Increase availability of ACh at receptor
sites
18. Acetylcholine (ACh)- Actions
Muscarinic
Eye
Sphincter (circular) muscle of iris
Contraction (miosis)
Ciliary muscle
Contraction for near vision
Spasm of accomodation
Increased aqueous outflow
Reduction in intraocular tension
19. Acetylcholine (ACh)- Actions
Nicotinic
Autonomic ganglia
Both parasympathetic & sympathetic ganglia stimulated
High dose ACh after atropine administration leads to
Tachycardia
Rise in BP
Skeletal muscles
Iontophoretic application of ACh to motor endplate leads
to skeletal muscle contraction
21. Choline Esters-Properties
Bethanechol
Not destroyed by cholinesterase (both true & pseudo)
Has mainly muscarinic actions (well antagonized by
atropine)
Negligible CVS effects
Acts chiefly on the bladder & bowels
Preferable to carbachol because of this partial selectivity
Carbachol
Not destroyed by cholinesterase (both true & pseudo)
More potent than bethanechol & methacholine
Muscarinic effects not adequately antagonized by atropine
22. Choline Esters-Properties
Carbachol(contd.)
Stimulates autonomic ganglia & skeletal muscles
Actions are most pronounced on the bladder & bowels
Used to stimulate bladder & intestines after surgery
Methacholine
Effective orally (though its absorption upon oral
administration is variable)
3 times more resistant to hydrolysis by true cholinesterase
w.r.t. ACh
Totally resistant to hydrolysis by pseudocholinesterase
Longer duration of action than ACh
23. Choline Esters- Uses
Acetylcholine not used because of its transient & non-
selective action
Others rarely used nowadays
Bethanechol has been used in
Postoperative paralytic ileus & gastric atony
Postoperative/postpartum nonobstructive urinary retention
Neurogenic bladder atony
Congenital megacolon, and
Gastroesophageal reflux
Methacholine was occasionally used to terminate
paroxysmal supraventricular tachycardia (PSVT)
24. Cholinomimetic Alkaloids
Pilocarpine(Tertiary amine)
Obtained from leaves of Pilocarpus microphyllus
Prominent muscarinic actions
Causes marked sweating, salivation & increases
other secretions
Applied to the eye, it penetrates cornea and
promptly causes miosis, ciliary muscle contraction
and fall in intraocular tension
Initial therapy (pilocarpine + physostigmine) in
acute angle-closure glaucoma
Used as 0.5-4% drops to treat chronic simple
glaucoma
25. Cholinomimetic Alkaloids
Muscarine
Occurs in poisonous mushrooms (Amanita muscaria &
Inocybe spp.)
Quaternary amine
Has only muscarinic actions
Not used therapeutically
Nicotine
Derived from the plant Nicotiana tabacum
Tertiary amine
Has only nicotinic actions
Lobeline
Plant derivative similar to nicotine
26. Cholinomimetic Drugs-Contraindications
Bronchial Asthma
Cholinergic drugs can precipitate an
asthmatic attack in susceptible individuals
as they can cause bronchoconstriction
Peptic Ulcer
Enhance gastric acid production and hence
can aggravate symptoms of acid peptic
disease
27. Cholinergic Drugs-1(Summary)
Two types of cholinergic receptors
(muscarinic & nicotinic)
Muscarinic receptors-smooth muscles/cardiac
muscle/glands/CNS
Nicotinic receptors-skeletal muscles/ganglia/
CNS
Cholinergic Drugs(Direct & Indirect-acting)
ACh actions on various organ systems
Choline esters & cholinomimetic alkaloids