cholinergic receptor Sem-04 Pharmacology-1

1. Drug table Cholinoceptor- Activating and cholinesterase-inhibiting Drugs.
Subclass Mechanism of
action
Clinical and other
application
Pharmacokinetics Toxicities,
Interaction
Direct-acting, muscarinic agonists
Bethanechol Activates muscarinic (M)
receptors increase IP3
and DAG
Bladder and bowel
atony, for
example, after surgery
or spinal
cord injury
Oral, IM activity
Poor lipid solubility:
does not
enter CNS
Duration: 0.3–2 h
All
parasympathomimetic
effects: cyclospasm,
diarrhea, urinary
urgency, plus
vasodilation, reflex
tachycardia, and
sweating
Pilocarpine Same as bethanechol increase salivation was
used in glaucoma
(causes miosis,
cyclospasm)
Oral, IM activity Good
lipid solubility, topical
activity in eye
Similar to bethanechol but
may cause
vasoconstriction via
ganglionic effect
Muscarine Same as bethanechol Alkaloid found in
mushrooms
Low lipid solubility
but readily
absorbed from gut
Mushroom poisoning of
fast-onset type
Direct-acting, nicotinic agonists
Nicotine Activates all nicotinic (N)
receptor+ opens Na+ -
Smoking cessation
(also used as
insecticide)
High lipid solubility,
absorbed by all routes
Generalized ganglionic
stimulation: hypertension,

2. Drug table Cholinoceptor- Activating and cholinesterase-inhibiting Drugs.
K+ channels in ganglia
and
neuromuscular end
plates
tachycardia, nausea,
vomiting, diarrhea
Varenicline A partial agonist at N
receptors
Smoking cessation High lipid solubility,
oral activity
Duration=12 hours
Hypertension, sweating,
sensory disturbance,
diarrhea, polyuria,
menstrual disturbance
Succinylcholine N-receptor agonist,
moderately
selective for
neuromuscular end
plate (NM receptors)
Muscle relaxation Highly polar, used IV.
Duration= 5-10 minutes
Initial muscle spasms and
postoperative pain.
Prolonged action in
person with abnormal
butyrylcholinesterase
Indirect-acting, alcohol
Edrophonium Inhibitor of cholinesterase
+ amplifier endogenously
released Ach
Reversal of NM block by
nondepolarizing drug.
Diagnosis of myasthenia
gravis
Highly polar + used IV +
Duration: 5–10 min
Increased
parasympathetic effects,
especially nausea,
vomiting, diarrhea,
urinary urgency

3. Drug table Cholinoceptor- Activating and cholinesterase-inhibiting Drugs.
Indirect-acting, carbamates
Neostigmine Like edrophonium plus
small direct nicotinic
agonist action
Reversal of NM block,
treatment of myasthenia
Moderately polar but
orally active
Duration: 2-4hours
Like edrophonium but
longer duration
Pyridostigmine Like edrophonium Treatment of myasthenia Moderately polar but
orally active
Duration: 4-8hours
Like edrophonium but
longer duration
Physostigmine Like edrophonium Reversal of severe atropine
poisoning (IV)
Occasionally used in acute
glaucoma (topical)
Lipid soluble
can be used topically in
the eye
Duration: 2-4hours
Like edrophonium but
longer duration plus CNS
effects: seizures
Indirect-acting, organophosphates
Parathion Like edrophonium Insecticide only
Duration: days to weeks
Highly lipid-soluble Highly dangerous
insecticide + causes all
parasympathetic effects
plus muscle paralysis and
coma

4. Drug table Cholinoceptor- Activating and cholinesterase-inhibiting Drugs.
Malathion Like edrophonium Insecticide and scabicide
(topical)
Duration: days
Highly lipid-soluble but
metabolized to inactive
products in mammals and
birds
Much safer insecticide
than parathion
Sarin, tabun, others Like parathion Nerves gases + terrorist
threat
Like parathion but more
rapid action
Rapidly lethal
Indirect-acting, for Alzheimer’s disease
Rivastigmine,
galantamine,
donepezil; tacrine is
obsolete
Cholinesterase inhibition
plus variable other
poorly understood
effects
Alzheimer’s disease Lipid soluble, enter CNS +
Half lives: 1.5–70 h
Nausea, vomiting
Sub type of M - receptor
M-receptor Location Cellular response Distribution Function:-
M1 receptor autonomic ganglia,
gastric and CNS
Gastric and salivary
gland, autonomic
ganglia, enteric
nerves, & selected
region of CNS.
PLC Cultivation,
depolarization &
excitation
1. Increase cognitive
function
2.Increase seizure
activity
3.Increase secretion

5. Drug table Cholinoceptor- Activating and cholinesterase-inhibiting Drugs.
4.Increase
autonomic ganglia
depolarization
M2 receptor Heart, GIT, CNS (in
the periphary)
Autonomic nerve
terminal, CNS,
heart,& smooth
muscle
Inhibition of adenyl
cyclose (ꜜcAMP) &
voltage gated ea2+
channel activation of
inwardly rectifying
K+
channel.
1. decrease heart
rate
2. Increase smooth
muscle contraction
3. Neural inhibition
of pheriphery
4. Increase
hypothesmia,
analgesic
M3 receptor Excrine gland and
smooth muscle
stimulatory effect
mediated by G
protein activation of
PLC to form second
message IP3 and
DAG
CNS, smooth
muscles, glands &
heart
1. Increase smooth
muscle contraction.
2. Increase secretion
of lacrimal, salivary,
and bronchial
pancreatic &
mucosal cell in GIT.
3. Inhibit dopamine
induced release
synthesis of nitric
oxide.
M4 receptor Tracheal smooth
muscle
Direct regulatory
action on K+
&
Ca2+
ions channel.
Tracheal smooth
muscle
1] Inhibit adenylate
cyclose
2] Analgesia
3] Catalytic activity

6. Drug table Cholinoceptor- Activating and cholinesterase-inhibiting Drugs.
4] Facilitates
dopamine release
M5 receptor Substania uigra PLC activation,
depolarization and
excitation
Low level of CNS and
periphery &
predominate
acetylcholine in
dopaminergic
neuron of Substania
uigra and ventral
area
1] mediates dilation
of cerebral arteries.
2] Regulates
dopamine release at
terminal with
stratium.
Sub type of N- receptor
N-
receptor
Location Distribution Membrane
Response
Molecular
Mechanism
Agonist Antagonist
Nm
(Nicotinic
muscle)
In the
neuromuscular
junction
Skeletal
neuromuscular
junction
Excitatory,
end plate
depolarization
and
contraction.
Increased Na+
& K+
ions.
Acetylcholine,
nicotine,
succinylcholine
Atracurium, α-
tubocuraline,
pancuronium,
α-conotoxin
Nn
(Neuronal)
In the ANS
ganlia
Autonomic
ganglia &
adrenal
medulla
Excitatory,
depolarisation
firing a post
ganglionic
neuron
Increased Na+
& K+
permeability.
Acetylcholine,
nicotine,
epibatidine
trimethaphan,
mecamylamine

7. Drug table Cholinoceptor- Activating and cholinesterase-inhibiting Drugs.
Cholinergic
receptor
Nicotinic
NN
Ganglia
Adrenal
medulla
NM
Neuro-
muscular
junction
Muscarinic
M1
Gastric
ganglia
CNS
M2
Heart
CNS
M3
Eye GIT Bladder
Glands
CNS
M4
CNS
M5
CNS