2. Cholinergic Drugs and Related
Agents
Mimic the action of acetylcholine or,
Blocks the action of acetylcholine (ACh)
*Cholinergc Drugs - stimulates the
parasympathetic nervous system (rest and
digest).
3. Acetylcholine
is one of many
neurotransmitters in
the autonomic nervous
system (ANS)
only neurotransmitter
used in the motor
division of the somatic
nervous system
5. Nicotinic Receptors
coupled directly to ion channels
first neurotransmitter isolated and purified in an active
form
It is a glycoprotein embedded into the polysynaptic
membrane that can be obtained from the electric organs
of the marine ray, Torpedo californica and the electric eel,
Electrophorus electricus.
When the neurotransmitter ACh binds to the nicotinic
receptor, it causes a change in the permeability of the
membrane to allow passage of small cations Ca2, Na, and
K. This depolarization results in muscular contraction at a
neuromuscular junction or, as occurs in autonomic
ganglia, continuation of the nerve impulse.
6. Nicotinic receptor subtypes
N1 N2
At the neuromuscular junction Found in autonomic ganglia
blocked by succinycholine, d-
tubocurarine, and decamethonium
and stimulated by
phenyltrimethylammonium
blocked by hexamethonium and
trimethaphan but stimulated by
tetramethylammonium and dimethyl
4-phenylpiperazinium
7. Muscarinic Receptors
play an essential role n regulating the function of
organs innervated by the autonomic nervous system
to maintain homeostasis.
Its action can result to stimulation/inhibition of the
organ system that is affected.
8. Muscarinic Receptor subtypes
M-
receptors
subtypes
M1 M2 M3 M4 M5
Other
name
neural Cardiac
muscarinic
receptors
Glandular
muscarinic
receptors
Location Exocrine
glands and
autonomic
ganglia
Atria and
conducting
tissue of the
heart
Exocrine
glands and
smooth
muscle
CNS Substantia nigra
(cns)
Function Affects arousal
attention, REM,
emotional
response,
affective
disorder
Cardiac
inhibition
Lacrimal,
salivary
Mostly
stimulatory
effect
Direct regulatory
action on K and
Ca ion channels
May regulate
dopamine release
at terminals within
the striatum
12. Cholinergic Neurochemistry
Cholinergic neurons synthesize, stores and releases
ACh . It describes any neuron which mainly uses
the neurotransmitter acetylcholine (ACh) to send its
messages.
Cholinergic neurons provide the primary source of
acetylcholine to the cerebral cortex, and are known
for their role in promoting cortical activation during
both wakefulness and during rapid eye movement
(REM) sleep.
Neurochemistry is the specific study
of neurochemicals including neurotransmitters and
other molecules (such as psychopharmaceuticals) that
influence the function of neurons.
13. CHOLINERGIC AGONIST
cholinergic agents;
parasympathomimetic;
mimics effect of parasympathetic nervous system
neuroransmitters
A substance (or ligand) is cholinergic if it is capable of
producing, altering, or
releasing acetylcholine ("indirect-acting") or
mimicking its behaviour at one or more of the
body's acetylcholine receptor types ("direct-acting").
14. Cholinergic Stereochemistry
is the study of the chemistry involved in the relative
spatial arrangement of cholinergic
atoms and molecules.
Has 3 techniques
15. X-ray crystallography
is a method of
determining the
arrangement
of atoms within
a crystal, in which a
beam of X-rays strikes a
crystal and diffracts into
many specific directions.
16. Nuclear magnetic resonance
a physical phenomenon in
which nuclei in a magnetic
field absorb and re-
emit electromagnetic
radiation.
This energy is at a
specific resonance frequen
cy which depends on the
strength of the magnetic
field and the magnetic
properties of the isotope of
the atoms
18. STRUCTURE – ACTIVITY RELATONSHIPS
is the relationship between the chemical or 3D
structure of a molecule and its biological activity. The
analysis of SAR enables the determination of the
chemical groups responsible for evoking a target
biological effect in the organism.
19. 3 Categories of the Alteration on
the Molecule
Onium group
Ester function
Choline moeity
22. CHOLINERGIC RECEPTOR ANTAGONISTS
blocks the neurotransmitter acetylcholine in
the central and the peripheral nervous system.
cholinergic blockers,
parasympatholytics or
anticholinergic
27. Cholinesterase inhibitors
bind to cholinesterase resulting in increased
acetylcholine in the synapses, causing increased
parasympathetic activity
Acetylcholinesterase - an enzyme that rapidly
breaks down the neurotransmitter, acetylcholine, so
that it does not over-stimulate post-synaptic nerves,
muscles, and exocrine glands
Acetylcholinesterase inhibitor - a chemical that
binds to the enzyme, cholinesterase, and prevents it
from breaking down the neurotransmitter,
acetylcholine.
28. 2 types of cholinesterase:
Acetylcholinesterase (AChE) – its inhibition
prolongs the duration of the neurotransmitter in the
junction and produces pharmacological effects similar
to those observed when ACh is administered.
Butyrylcholinesterase (BuChE) –
(pseudocholinesterase), is located in human plasma.
Has catalytic property similar to AChE
29. 2 TYPES OF ACETYCHOLINETRANFERASE
INHIBITORS
REVERSIBLE INHIBITORS– has therapeutic
application
IRREVERSIBLE INHIBITORS – these chemicals are
nerve poisons and had been use in warfare,
bioterrorism, and as agricultural insecticides. They
permit ACh to accumulate at nerve endings and
exacerbate ACh-like actions.
34. Galantamine
Leucojum aestivum
belonging to the
Amaryllidaceae family and
from the bulbs of the
daffodil, Narcissus
pseudonarcissus;
no effect on
butyrylcholinesterase; acts
at allosteric nicotinic sites,
further enhancing its
cholinergic activity.
35. Rivastigmine
– the FDA approved its
use in mild-to-moderate
Alzheimer’s disease in
April 2000.
In July 2007, it was
granted approval for use
in managing mild-to-
moderate dementia
associated with
Parkinson’s disease.
36. Irrevrsible Inhibitors
Isofluorphate, USP
(Floropryl) - Stable in
peanut oil (1 yr).
Solutions in peanut oil
can be sterilized by
autoclaving;
Should be stored in
glass containers,
discoloration when
decomposed;
treatment of glaucoma
38. Parathion
- (Thipos);
Decomposed at pH
above 7.5;
causes poisoning by
inhalation or dermal
absorption;
Used as an agrcultural
insecticide
39. Hexaethyltetraphosphate (HETP) and
Tetraethylpyrophosphate (TEPP)
- Developed by the Germans
during WWII;
Insecticide against aphids;
Fruit trees or vegetables
sprayed retain no harmful
residue after a period of a few
days or weeks, depending on
the weather conditions.;
Workers spraying with these
agents should use extreme
caution so that vapors are
not breathed and none of the
vapor or liquid comes in
contact with the eyes or skin.
40. CHOLINERGIC BLOCKING AGENTS
Anticholinergic action by drugs and chemicals
apparently depends on their ability to reduce the
number of free receptors that can interact with Ach.
Some theories indicate that the amount of drug-
receptor complex formed at a given time depends on
the affinity of the drug for the receptor and that a
drug that acts as an agonist must also possess another
property called efficacy or intrinsic activity.
