1. The document discusses drugs that act on the autonomic nervous system, including adrenergic neurotransmitters, receptors, and sympathomimetic agents that act directly or indirectly on those receptors. 2. It provides details on specific drugs like epinephrine, norepinephrine, dopamine, beta blockers like propranolol, and ergot alkaloids and their mechanisms of action and uses. 3. The document also discusses structure-activity relationships that contribute to the selectivity and duration of action of various adrenergic and beta blocker drugs.

1. DRUGS ACTING ON
AUTONOMIC NERVOUS
SYSTEM
DR TC LALHRIATPUII
ASSISTANT PROFESSOR, DEPARTMENT OF
PHARMACY, RIPANS AIZAWL

2. Adrenergic Neurotransmitters

3. Adrenergic receptors (α & β) and their
distribution
RECEPTOR NAME DISTRIBUTION
α1 Vascular smooth muscle, visceral smooth muscle,
radial smooth muscle of iris, CNS neurons
α2 Some presynaptic terminals, pancreatic islets,
platelets, ciliary epithelium, smooth muscles, CNS
neurons
β1 Myocardium, some presynaptic terminals, CNS
neurons
β2 Visceral smooth muscle,vascular smooth muscle
,liver, myocardium, skeletal muscle, some presynaptic
terminals, CNS neurons

4. Sympathomimetic agents
• Sympathomimetic agents are stimulant compounds
which mimic the effects of endogenous agonists of
the sympathetic nervous system.
• They are classified as directly acting (act directly on α
or β receptors), indirectly acting (act by providing
more norepinephrine to act on α or β receptors),
or mixed acting( act by both mechanisms).

5. SAR OF SYMPATHOMIMETIC AGENTS

13. Direct acting sympathomimetic agent
• They act through complexation with specific
receptors they are represented by nor-adrenaline
for the activation of beta receptor phenolic
hydroxy function in meta at the catechol nucleus
and at the side chain hydroxide in beta and amine
especially the phenolic hydroxyl seems to be
relatively more critical for activation of beta
receptors

14. Nor- epinephrine
MOA: Norepinephrine agonistic
action on alpha-adrenoceptors and
beta-1 adrenoceptors increases the
heart rate and contractility and
produces vasoconstriction,
resulting in increased systemic
blood pressure and coronary blood
flow.
Uses: Norepinephrine is similar to
adrenaline. It works by constricting
(narrowing) the blood vessels and
increasing blood pressure and
blood glucose (sugar) levels.

15. Epinephrine
MOA: Epinephrine stimulates α-, β1,
and β2 adrenergic receptors,
resulting in local vasoconstriction
and relief of nasal congestion.
Uses: This medication is used in
emergencies to treat very serious
allergic reactions to insect
stings/bites, foods, drugs, or other
substances. Epinephrine acts quickly
to improve breathing, stimulate the
heart, raise a dropping blood
pressure, reverse hives, and reduce
swelling of the face, lips, and throat.

16. Phenylephrine
MOA: Phenylephrine is a potent,
direct acting α adrenergic agonist
with virtually no β adrenergic
activity.
Uses: Phenylephrine is used to
relieve nasal discomfort caused by
colds, allergies, and hay fever. It is
also used to relieve sinus
congestion and pressure.

17. Dopamine
MOA : Dopamine stimulates both adrenergic
and dopaminergic receptors. Lower doses
mainly cause dopaminergic stimulation
and produce renal and mesenteric
vasodilation. Higher doses also cause both
dopaminergics and β1 adrenergic
stimulation and produce cardiac
stimulation and renal vasodilation.
Large doses also stimulate α adrenergic
receptors.
USES: It works by improving the pumping
strength of the heart and improves blood
flow to the kidneys. It is used to treat
certain conditions that occur in shock,
which may be caused by heart attack,
trauma, surgery, heart failure, kidney
failure, and other serious medical
conditions.

18. Methyldopa
MOA: Methyldopa may stimulate
central α2 adrenoceptors or cause
false neurotransmission ( alpha –
methyl norepinephrine) that results
in reduced sympathetic outflow to
the heart, kidneys, and peripheral
vasculature and, therefore,
decreased blood pressure.
Uses: This medication is used alone or
with other medications to treat high
blood pressure (hypertension).
Lowering high blood pressure helps
prevent strokes, heart attacks, and
kidney problems.

19. Clonidine
MOA: Clonidine is a centrally
acting alpha 2 adrenergic
agonist indicated for the
treatment acute and chronic
hypertension.
Uses: Clonidine is used to treat
high blood pressure,
attention deficit hyperactivity
disorder(ADHD), drug-
withdrawal (alcohol, opiods,
or smoking).

20. Dobutamine
MOA: Dobutamine directly
stimulates β1 receptors of the
heart to increase myocardial
contractility and stroke volume,
resulting in increased cardiac
output.
Uses: Dobutamine is used to treat
acute but potentially reversible
heart failure, such as which occurs
during cardiac surgery or in cases
of septic or cardiogenic shock,

21. Isoproterenol
MOA: Isoproterenol effects
on the cardiovascular system are
due to its agonistic action on β1
adrenoceptors in the heart &
β2 adrenoceptors in arteriolar
smooth muscle.
Uses: Isoproterenol is a
bronchodilator used as an
inhaler to treat conditions such
as asthma, bronchitis and
emphysema

22. Terbutaline
MOA: Terbutaline relaxes bronchial
smooth muscle by stimulating β2
adrenergic receptors.It inhibits
the release of hypersensitivity
mediators, especialy from mast
cells.
Uses: Terbutaline is used to prevent
and treat wheezing, shortness of
breath, and chest tightness caused
by asthma, chronic bronchitis and
emphysema.It is a class of
medications called beta agonists.

23. Salbutamol
MOA: Salbutamol is a β2
receptor agonist which
relaxes bronchial smooth
muscle.
Uses: It is used to treat
asthma, chronic
bronchitis, emphysema
and to prevent exercise
related asthma.

24. Bitolterol
MOA: Bitolterol is an
adrenergic β2 agonist
which leads to relaxation
of the smooth muscles
causing bronchodilation.
Uses: It is used as
bronchodilator in chronic
lung disorders.

25. Naphazoline
MOA: Naphazoline stimulates α
adrenergic receptors in the
arterioles of the conjunctiva and
the nasal mucosa to produce
vasoconstriction.
Uses: Naphazoline is a
decongestant used to relieve
redness, puffiness, and
itchy/watering eyes due to
colds, allergies, or eye
irritations.

26. Oxymetazoline
MOA: Oxymetazoline
stimulates α adrenergic
receptors in the arterioles of
the nasal mucosa to produce
vasoconstriction.
Uses: Oxymetazoline is used
to relieve nasal discomfort
caused by colds, allergies, and
hay fever. It is used to relieve
sinus congestion and pressure.

27. Xylometazoline
MOA: It stimulates α-
adrenergic receptors in the
arterioles of the conjunctiva
and the nasal mucosa to
produce vasoconstriction.
Uses: It is used for temporary
relief of congestion in the
noise caused by various
conditions including the
common cold, sinusitis, hay
fever, and allergies.

28. Indirect acting agents
MOA: Hydroxyamphetamine
causes the release of
norepinephrine from
adrenergic nerve terminals,
resulting in mydriasis.
Uses: It is used medically in eye
drops to dilate the pupil, so
that the back of the eye can
be examined.
Hydroxyamphetamines

29. Pseudoephedrine
MOA: Pseudoephedrine exerts
agonistic action adrenoceptors on
α in the arterioles, constricts
arterioles in mucous membrane,
and thereby reduces mucous
membrane swelling and
congestion.
Uses: Pseudoephedrine is used
to relieve nasal congestion caused
by colds, allergies, and hay fever.
It is also used to temporarily
relieve sinus congestion and
pressure.

30. Why pseudoephedrine is banned?
• Pseudoephedrine can be misused as an ingredient for the illicit
manufacture of methamphetamines
• In 2005, the FDA created the Combat Methamphetamine
Epidemic Act, which banned over-the-counter sales of cold
medicines that included the ingredient pseudoephedrine,
requiring them to be sold behind the counter
• Pseudoephedrine is most dangerous when it is used in the
manufacture of methamphetamines. The conversion of
pseudoephedrine into methamphetamine is the most common
way for people to get high using pseudoephedrine.
• Methamphetamine is a powerful stimulant that can be highly
addictive and easily abused. People who abuse
methamphetamines take the drug by inhaling or smoking it,
swallowing it in pill form, snorting crushed or powder forms of
the drug, or injecting powder that has been dissolved in water.

31. Propylhexedrine
MOA: Propylhexedrine
stimulates α-adrenergic
receptors in nasal mucosal
vasculature to produce
nasal vasoconstriction that
results in nasal
decongestion.
Uses: It is used to treat acute
nasal congestion related to
common cold, allergies and
hay fever.

32. Agents with mixed mechanism
MOA: Ephedrine releases tissue of
norepinephrine and thereby
produces α and β adrenergic
stimulation producing mucosal
vasoconstriction and
decongestion.
Uses: Ephedrine is a CNS stimulant
used to treat breathing problems (
as a bronchodilator), nasal
congestion( as a decongestant), low
blood pressure problems(
orthostatic hypotension), or
myasthenia gravis.
Ephedrine

33. METARAMINOL
MOA: Metaraminol acts through
peripheral vasoconstriction by
acting as a pure α-1 adrenergic
receptor agonist, consequently
increasing systemic blood
pressure(both systolic &
diastolic).
Uses: It is used in the prevention
and treatment of hypotension,
particularly as a complication of
anesthesia.
Metaraminol

34. Adrenergic Antagonist
MOA: Tolazoline is a direct peripheral
vasodilator with α-adrenoceptor
blocking activity. It causes
peripheral vasodilation and
decreases peripheral resistance by
vascular smooth muscle relaxation.
It inhibits catecholamine –induced
hypertension via indirect action.
Uses: It is a vasodilator that is used to
treat spasms of peripheral blood
vessels.
Tolazoline

35. Phentolamine
MOA: Phentolamine non-selectively
antagonises the circulation of
epinephrine and norepinephrine
resulting in reduced BP. It directly acts
on the vascular smooth muscle and
increase the strength of muscular
contraction of the heart.
Uses: It is used to reverse numbness after
oral and dental procedures, to prevent
and control episodes of dangerously
high blood pressure, to prevent and
treat accidental injection of certain
drugs under the skin, and also to
diagnose a condition called
pheochromocytoma.

36. Phenoxybenzamine
MOA: Phenoxybenzamine produces
long-lasting, non-competitive α-
adrenergic blockade of
postganglionic synapses in exocrine
glands and smooth muscle. It
relaxes the urethra and increases
the opening of the bladder.
Uses: It is used to treat episodes of
high blood pressure and sweating
related to pheochromocytoma.

37. Prazosin
MOA: Prazosin competitively
blocks postsynaptic α-1
adrenoceptors of veins and
arterioles, causing vasodilation,
reduction in BP, and total
peripheral resistance, usually
without reflex tachytardia.
Uses: Prazosin is used alone or in
combinations to treat high blood
pressure.

38. Dihydroergotamine
MOA: It works by tightening the
blood vessels in the brain and by
stopping the release of natural
substances in the brain that
cause swelling.
Uses: It is used to treat migraine
headaches.

39. Methysergide
MOA: Methysergide is a serotonin
antagonist that acts on the CNS,
causing direct stimulation of
smooth muscles and leading to
vasoconstriction.
Uses: It is used exclusively to treat
episodic and chronic migraine and
for episodic and chronic cluster
headaches.

40. BETA ADRENERGIC BLOCKERS
• Beta adrenergic blocking agents: A class of drugs, also called beta blockers, that
block beta-adrenergic substances such as adrenaline (epinephrine), a key agent in
the "sympathetic" portion of the autonomic (involuntary) nervous system.
• By blocking the action of the sympathetic nervous system on the heart, these agents
relieve stress on the heart. They slow the heart beat, lessen the force with which the
heart muscle contracts and reduce blood vessel contraction in the heart, brain, and
throughout the body.
• Beta blockers can serve to treat abnormal heart rhythms (cardiac arrhythmias). They
are used specifically to prevent abnormally fast heart rates (tachycardias) or
irregular heart rhythms such as premature ventricular beats.
• Since beta blockers reduce the demand of the heart muscle for oxygen and
the chest pain of angina pectoris occurs when the oxygen demand of the heart
exceeds the supply, beta blockers can be useful in treating angina. They have also
become an important drug in improving survival after a person has had a heart
attack.
• Thanks to their effect on blood vessels, beta blockers can lower the blood pressure
and be of value in the treatment of hypertension.
• Other uses for beta blockers include the prevention of migraine headaches and the
treatment of certain types of tremors (familial or hereditary essential tremors).

41. PROPRANOLOL
Mechanism of Action: Competitively blocks both β1 and β2
adrenergic receptors. When access to β-receptor sites is
blocked by Propranolol HCl, the chronotropic, inotropic, and
vasodilator responses to beta-adrenergic stimulation are
decreased proportionately.
Uses: Propranolol belongs to a group of medicines called
beta blockers. It's used to treat heart problems, help with
anxiety and prevent migraines.

42. SAR of beta blockers
Propanolol

43. METIPRANOLOL
MOA: Although it is known that metipranolol
binds the beta1 and beta2
adrenergic receptors, the mechanism
of metipranolol's action is not
known. It has no significant intrinsic
sympathomimetic activity, and has
only weak local anesthetic
(membrane-stabilizing) and
myocardial depressant activity. It
appears that the ophthalmic beta-
adrenergic blocking agents reduce
aqueous humor production, as
demonstrated by tonography and
fluorophotometry. A slight increase
in aqueous humor outflow may be
an additional mechanism.
USES: Ophthalmic metipranolol is used to treat
glaucoma, a condition in which increased pressure in
the eye can lead to gradual loss of vision

44. Atenolol
• The phenyl acetamide is the main moiety which bind or inhibit
adrenergic activity when the isopropyl amino group bind with
phenyl acetamide.
• The presence of 2 alkyl moiety at the centre atom with the
presence of amine moiety is essential for first metabolism and
develop increase duration of action.

45. Betazolol
MOA: Betaxolol selectively blocks catecholamine stimulation
beta(1)-adrenergic receptors in the heart and vascular smooth
muscle. This results in a reduction of heart rate, cardiac output,
systolic and diastolic blood pressure, and possibly reflex
orthostatic hypotension.
USES: Ophthalmic betaxolol is used to treat glaucoma, a
condition in which increased pressure in the eye can lead to
gradual loss of vision. Betaxolol is in a class of medications
called beta blockers. It works by decreasing the pressure in the
eye.

46. Bisoprolol
• Increasing the side chain length of the side chain prevents
appropriate binding of the required functional groups to the same
receptors side.
• Side chain of aryloxypropanolamines can adopt a conformation
that places the hydroxyl and amine groups into the same position
in space.
• Aryloxypropanolamines permits a close overlap with the
arylethanomine side chain.
• Aryloxypropanolamines are more potent than
aryloxyethanolamines.

47. Esmolol
MOA: By blocking the action of adrenergic
activity of epinephrine and
norepinephrine, it decreases inotropic
contractility, heart rate, and
conduction. Esmolol increases
atrioventricular refractory time, decreases
oxygen demand of the myocardium, and
decreases atrioventricular conduction.
USES: Esmolol is used to control rapid
heartbeats or abnormal heart rhythms.
This medicine is also used to treat fast
heartbeat and high blood pressure during
surgery, after surgery, or during other
medical procedures

48. Metoprolol
MOA: Metoprolol belongs to a class of drugs
known as beta blockers. It works by blocking
the action of certain natural chemicals in your
body, such as epinephrine, on the heart and blood
vessels. This effect lowers the heart rate, blood
pressure, and strain on the heart.
USES: Metoprolol is used alone or in
combination with other medications to treat
high blood pressure. It also is used to prevent
angina (chest pain) and to improve survival
after a heart attack. Metoprolol also is used in
combination with other medications to treat
heart failure.

49. Labetolol
MOA: Labetalol competitively binds to alpha-1-
adrenergic receptors in vascular smooth muscle,
thereby inhibiting the adrenergic stimulation of
endothelial cell function and vasoconstriction in
peripheral blood vessels.
USES: It's used to treat high blood pressure,
including high blood pressure in pregnancy. It can
also be used to prevent chest pain caused by
angina.

50. Carvedilol
MOA: Carvedilol works by blocking the action of certain
natural substances in your body, such as epinephrine, on
the heart and blood vessels. This effect lowers your heart
rate, blood pressure, and strain on your heart.
USES: Carvedilol is used to treat high blood pressure and
heart failure. It is also used after a heart attack to improve
the chance of survival if your heart is not pumping well.
Lowering high blood pressure helps prevent strokes, heart
attacks, and kidney problems