1. Drugs acting on Autonomic
Nervous System
~ Aryan Patel
B.Pharm

2. Topics for discussion
• Introduction
 Nervous System
 Autonomic Nervous System
• Adrenergic Neurotransmitters
• Sympathomimetic agents

3. Introduction

4. Nervous System
 The command system of one’s body.
 Regulates the body’s other systems.
 The Nervous System is a complex network of nerves and
cells that carry messages to and from the Brain and Spinal
cord to various parts of the body.
 Sub-divided into :
1. Central Nervous System
2. Peripheral Nervous System

5. Central Nervous System
• Body’s processing System
• Made up of Brain and Spinal Cord
• It combines information from the
entire body and coordinates activity
across the whole organism.

6. Peripheral Nervous System
 Parts of Nervous System outside the
Brain and Spinal Cord
 Includes Cranial and Spinal Nerves,
their roots , branches , peripheral
nerves and neuromuscular junctions.
 Consist of Autonomic and Somatic
Nervous System

8. Autonomic Nervous System
 Also referred as Vegetative Nervous System
 Regulates body’s unconscious body processes
Or
 The system works automatically (autonomous) without a person’s conscious effort
 Some body processes controlled by ANS are :-
1. Blood pressure
 Heart and Breathing rates
1. Body temperature
2. Digestion
3. Urination
4. Metabolism

9. Autonomic Nervous System is
subdivided into :-
 Maintenance functions
 Rest and digest response
 Counterbalances sympathetic functions
 Allow body to function under stress
 Fight and flight response
 Intense skeletal muscle activity
Sympathetic Nervous System Parasympathetic Nervous System

12. Best way to lose your weight :-
https://www.digistore24.com/redi
r/311818/AFFILIATE/CAMPAIGNKEY

13. Adrenergic
Neurotransmitters

14. Overview
Defination :-
 Drugs that stimulates the sympathetic Nervous System
are called Adrenergics .
 Also called Adrenergic agonists or Sympathomimetic because
they mimic the effects of SNS neurotransmitters.
• Sympathomimetics :- Compounds that produce effects similar to Sympathetic
Nervous Activity are known as Sympathomimetics
Synonym :-
 Adrenergic stimulants

15. Neurotransmitters
 Chemical messanger
 Transmit signals from one Neuron cell to the next
target cell (Nerve cell , muscle cell or a gland)
 Sympathetic -> Adrenergic Neurotransmitters
 Parasympathetic -> Cholinergic Neurotransmitters
 Both works Antagonistically to maintain homeostasis.

16. Adrenergic Neurotransmitters are collectively
called Catecholamines.
• They are of 3 types :-
Noradrenaline (NA) –
 Also called Norepinephrine
 At post ganglionic Sympathetic sites (expect sweat glands , hair follicles)
and in certain areas of brain .
Adrenaline (Adr) –
 Also called Epinephrine
 Secreted by adrenal medulla
Dopamine (DA) –
 Transmitter in basal ganglia , Anterior pituitary
 Gives feeling of pleasure, motivation, movement and addiction

17. Structure
 • Chemically these are called Catecholamines (CAs) because of Catechol group in their structure.
• Catechol ring

18. Synthesis of Catecholamines
• Sympathomimetic – Agents that activates Adrenergic receptors
• Sympatholytic – Agents that blocks the activation of Adrenergic receptors
 Catecholamines occur naturally in our body.
 The synthesis takes place in Adrenergic and Dopaminergic neurons in the
CNS , in Sympathetic neurons in ANS and in the Adrenal medulla
• Synthesis -
1. L-Phenylalanine is converted into L-tyrosine by Phenylalanine hydroxylase,
2. L-Tyrosine is converted into L-DOPA by tyrosine 3-hydroxylase ,
3. L-DOPA is converted into dopamine by the enzyme aromatic L-amino acid decarboxylase
(AADC),
4. Dopamine is converted into nor epinephrine by the enzyme dopamine ẞ- hydroxylase
(DBH),
5. Nor epinephrine is converted into epinephrine by the enzyme phenyl ethanolamine N-
methyltransferase (PNMT).

20. Release
 Arrival of an impulse at Adrenergic nerve ending
 The voltage gated calcium channels get opened
 Influx of Ca++ ions
 Triggered Ca++ causes rupture of synaptic vesicles by a process
called Exocytosis.
 Release of Norepinephrine(NE) into synaptic cleft (NEJ – Neuroeffector junction)
 NE binds with Alpha receptors or Beta receptors present on pre-synaptic
and post-synaptic membrane
 Initiation of pharmacological response

21. Catabolism of Catecholamines
 Endogenous and Exogenous Catecholamines are metabolized
mainly by 2 enzymes –
1. MAO :- Mono – Amino Oxidase
2. COMT :- Catechol – O – Methyl Transferase
 Main final metabolite of Adrenaline and Noredrinaline is
3- Methoxy – 4 – Hydroxymandelic acid i.e. Vanillylmandelic
acid (VMA).

24. Adrenergic receptors and
their distribution
 Introduced by Raymond Ahlquist in 1948
 Activated by same Catecholamines(E,NE) , but displays
opposite phenotypes in the body
 Are memberane bound G-protein coupled receptors
 Classified into 2 types :-
1. Alpha receptors
2. Beta receptors

25. Distribution with their actions
Alpha receptor –
• They are subdivided into two types:
1. Alpha -1 receptor – Found in smooth muscle, heart, and
liver
Effects - vasoconstriction, intestinal relaxation, uterine
contraction and pupillary dilation.
2. Alpha -2 receptor - Found in platelets, vascular smooth
muscle, nerve termini, and pancreatic islets .
Effects - platelet aggregation, vasoconstriction, and
inhibition of nor-epinephrine release and of insuline
secretion

26. Beta receptor –
• There are three known types of beta receptor,
designated B1, B2 and B.3.
1. Beta – 1 receptors - Located mainly in the heart
Effects – Increases heart rate, renin release, and lipolysis.
2. Beta - 2 receptors – Located mainly in the lungs, gastrointestinal
tract, liver, uterus, vascular smooth muscle, and skeletal muscle
Effects – Smooth muscle relaxation , vasodilation
3. Beta – 3 receptors - Located in fat cells
Effects - Lipolysis, thermogenesis, and relaxation of intestinal smooth
muscle.

27. Best way to lose your weight :-
https://www.digistore24.com/redir/31
1818/AFFILIATE/CAMPAIGNKEY

28. Sympathomimetic
agents

29. Overview
 Also called Adrenergic agonists
 Mimic the effect of Sympathetic Nervous System
 Sympathomimetic drugs are used to treat cardiac arrest ,
low blood pressure , or even delay premature labor ,
among other drugs .

30. Structure Activity Relationship (SAR)
 Relationship between chemical structure of a molecule
and it’s biological activity
 Allows modification on the effect of potency of a
Bioactive compound by changing it’s chemical structure
 Many of Sympathomimetic drugs contain B – Phenyl
ethylamine as their parent structure.
 It contains a catechol ring, B-carbon with hydroxyl group(-
OH) and a-Carbon containing an amine group(-NH₂).

31. • Structurally modification or substitution can be occur on :-
1. Catechol ring
2. Beta – carbon
3. Alpha – carbon
4. Amino group
Catechol ring: It is responsible for maximum activity and potency of Alpha and beta
receptors . Ex: Phenylephrine (low potency), Epinephrine (high potency)
Absence of hydroxyl group (-OH) increases CNS activity and Blood Brain Barrier crossing
ability of drug Ex: Amphetamine
B-carbon: Hydroxyl group decreases the CNS activity and increases the alpha and beta
activity of the drug Ex: Ephedrine
A-carbon: If substituted, then decrease in activity and longer duration of action is
observed Ex: Amphetamine
Amine group: Primary and secondary amines show high selectivity Ex: Adrenaline
Alkyl substitution increases the size of compound that shows high selectivity towards
Beta receptors Ex: Isoprenaline, Salbutamol

32. Classification of
Sympathomimetic agents :-
1. Direct acting
2. Indirect acting
3. Mixed acting

34. Direct acting drugs :-
 Able to activate Adrenergic receptors (Alpha and Beta)
 Rapid actions produced and of short duration

35. 1.Nor-epinephrine
• Chemical formula: C8H11NO3
• Mol. Mass: 169.18 g/mol
• Properties:
 It is a white or brownish-White, crystalline powder, slightly soluble in ethanol and
soluble in water.
• Mechanism of action:
 Potent at a- receptor (Less potent adrenalins). Also effect on ẞ1- receptor but no
effect on ẞ2- receptor.
• Uses:
1. Strong Vasoconstriction properties. So it is used in local anaesthetic solutions for
dental use.
2. Its principle use is to support blood in various acute hypotensive states, especially
in myocardial shock.
• Storage:
 It becomes colored on exposure to air and light. It should be stored in well-closed
airtight containers, under an inert gas and protected from light.

36. Norepinephrine

37. 2. Epinephrine
 Adrenaline is a catecholamine and belongs to the family of biogenic amines.
• Chemical formula: C9H13NO3
• Mol. Mass: 183.204 g/mol
• Properties:
 It is a white or creamy white, sphaero-crystalline powder. It dissolves in solutions of potassium
hydroxide, and of sodium hydroxide, but sparingly soluble in water, insoluble in ethanol and ether.
• Mechanism of action:
 It directly bind with A1 , B1 and B2 receptor.(Potent for all) It given by oral route in the form of pro-
drug (Pivalic acid) to prevent first pass metabolism.
• Uses:
1. It is used to prevent bleeding during surgery or in case of inner organ bleeding. Because
adrenaline leads to constriction of blood vessel.
2. It is administered in combination with local anesthetics. In this combination, anesthetics have
long-lasting effect and can be administered in smaller doses.
• Storage:
 Epinephrine is light sensitive and easily oxidized on exposure to air because of the catechol ring
system. To minimize oxidation, solutions of the drug are stabilized by the addition of a reducing
agent. Ex- sodium bisulphite.
 Adrenaline should be stored in well-closed airtight containers, which is preferably filled with
nitrogen, and protected from light.

38. Epinephrine

39. 3. Phenylephrine
 Phenylephrine is available as hydrochloride salt.
• Molecular formula: C9H14NO2CL
• Molecular Weight: 203.67 g/mol
• Properties:
 It is a white, odorless, bitter taste, crystalline powder. It is soluble in water, alcohol, and glycerol,
• Mechanism of action:
 Bind at a1 receptor.
 No action on B receptor
• Storage:
 It should be stored in airtight container to protect from light
• Synthesis:
1. Phenol with 2-chloro acetyl chloride gives 2-chloro-1[3-hydroxy phenylethanone.
2. 2-chloro-1[3-hydroxy phenyl] ethanone react with NH2CH3 it gives 1-(3-hydroxyphenyl)2- (methyl amino) ethanone.
3. 1-(3-hydroxyphenyl)2- (methyl amino) ethanone under go reduction reactions (addition of hydrogen) to form Phenylephrine.
• Uses:
1. Phenylephrine is a selective al-receptor agonist. Oral absorption is not reliable and so it is given parenterally or topically as eye
or nasal drops.
2. Phenylephrine is used as a nasal decongestant.
3. Vasoconstriction of arterioes, Iris and constriction of Uterus.

40. Synthesis :-

41. Phenylephrine

42. 4. Dopamine
 It is a neurotransmitter that helps to regulate movement And emotional response.
• Chemical formula: C8H11NO2
• Mol. Mass: 153.18 g/mol
• Properties:
It is a white or almost white crystalline powder, soluble in alcohol, sparingly soluble in
acetone and methylene chloride, but freely soluble in water.
• Mechanism of action:
 It is directly stimulate B1 and A1 receptor. (Dual acting Drug)
• Storage:
 It should be stored in well- closed airtight containers, protected from light.
• Uses:
1. It is used in the treatment of shock.
2. It is also used in heart attack,trauma, surgery and other serious medical condition.

43. Dopamine

44. 5. Methyldopa
• Chemical formula: C10H13NO4
• Mol. Mass: 211.215 g/mol
• Properties:
 Methyldopa is a white to yellowish white, odorless fine powder, and is soluble in
water.
• Mechanism of action:
 Methyldopa is converted into a- methyl nor-epinephrine by enzyme
dopamine beta hydroxylase and bind with a2.
• Uses:
1. This medication is used alone or with other medications to treat high blood
pressure.(Hypertension)
2. Lowering blood pressure helps to prevent strokes, heart attacks and kidney
problems.
• Storage:
 It should be stored in well- closed airtight containers, protected from light.

45. Methyldopa

46. 6. Clonidine
• Molecular weight: 0.093 g/mol
• Chemical Formula: C9H9Cl12N3
• Properties:
 Clonidine is an imidazole derivate that acts as an agonist of alpha-2 adreno
receptors.
• Mechanism of action:
 It is centrally acting on a2 receptor.
• Uses:
1. It is used in the treatment of hypertension, nasal decongestant, open Eye
glaucoma .

47. Clonidine

48. 7. Dobutamine
 It is a synthetic catecholamine.
• Molecular Formula: C18H23NO3
• Molecular Weight: 451.5 g/mol
• Properties:
 It is a white or almost white crystalline powder, sparingly soluble
in water and alcohol and soluble in methanol.
• Mechanism of action:
 It directly stimulate B1 as well as A1 receptor.(Dual acting drug)
• Uses:
1. It is used in ICU for the treatment of congestive Heart failure,
Cardiogenic shock, pulmonary oedema and to increase cardiac output.
• Storage:
 It should be stored in well-closed airtight containers, protected from light.

49. Dobutamine

50. 8. Isoproterenol (Isoprenaline)
 Isoproterenol hydrochloride is a recent compound. It is a non selective and
synthetic catecholamine.
• Molecular Formula: C11H17NO3
• Molecular Weight: 247.72 mol
• Properties:
 It is a white or almost white crystalline powder, freely soluble in water, sparingly
soluble in alcohol, practically insoluble in methylene chloride.
• Mechanism of action:
 It is a nonselective B agonist and has strong B1 and B2 agonist activity.
 B1- Increase cardiac output
 B2- Increase bronchodilation.
• Uses:
1. Its primary use is in the treatment of bronchial asthama
2. It is a CNS stimulant and peripheral vasodilator.
Storage:
 It should be stored in well-closed airtight containers, protected from light.

51. Isoprenaline

52. 9. Terbutaline
 Terbutaline is a non- catecholamine therefore is resistant to COMT.
• Molecular Formula: C12H19NO3
• Molecular Weight: 225.288 g/mol
• Properties:
 It exists as a gray-white crystalline powder, odorless and with a bitter taste,
soluble in water and alcohol.
• Mechanism of action:
 It bind with B2 receptor. It is better than Isoprenaline drug.
• Storage:
 It should be stored in well-closed airtight containers, protected from light.
• Uses:
1. Terbutaline is a brochodialator medicine that is used to treat symptoms such as
Wheezing, shortness of breath, chest tightness, breathing difficulties, coughing
etc. associated with asthma.
2. It is used to treat an acute attack of asthma as well as for prevention of futher
asthma attacks.

53. Terbutaline

54. 10. Salbutamol
• Chemical formula: C13H21NO3
• Mol. Mass: 239.311 g/mol
• Mechanism of action:
 Directly bind with B2 receptor.(Selective B2 agonist)
Properties:
 It is a white or almost white crystalline powder, sparingly soluble in water,
but freely soluble in ethanol.
• Uses:
1. It has been used to arrest premature labor.
2. It is used only as a bronchodilator and is the drug of choice in the treatment
of bronchial astlungs
3. It is also used to treat emphysema.(A condition that involves damage to the
walls of the air sacs i.e alveoli of lungs)
• Storage:
 It should be stored in well-closed airtight containers, protected from light.
• Dose:
 By oral inhalation the adult dose is 100 microgram, followed by
second dose after 5 min, if required.

55. Synthesis:-
 Salbutamol can be prepared from an acetophenone derivative which is itself
derived from Salicylic acid ( Hence the “Sal” in Salbutamol)

56. Salbutamol

57. 11. Bitolterol
 It is a new B2 adrenergic agonist.
• Molecular formula: C28H31NO5
• Molecular mass: 461.558 g/mol
• Properties:
 Bitolterol is consider as a pro drug for colterol.
• Mechanism of action:
 Directly bind with B2 receptor.(Selective B2 agonist)
• Uses:
1. Used as methane sulfonate salt for relief of bronchospasm in conditions such
as asthma, chronic bronchitis and emphysema.
• Storage:
 It should be stored in well-closed airtight containers, protected from light.

58. Bitolterol

59. 12. Naphazoline
 It is a rapid and direct acting sympathomimetic drug and exist in an ionised form.
 Chemically it is 2-(1-naphthylmethyl)-2-imidazoline and an imidazoline derivatives.
• Molecular Formula: C14H14N2
• Molar Mass: 210.28 g/mol.
• Properties:
 It is a white crystalline, odourless, and bitter compound.
 The salt is soluble in water and in alcohol. They essentially exist in an ionized form at physiological pH
because of the very basic nature of the imidazoline ring (pKa 9 to 10).
• Mechanism of action:
 It is a powerful a- receptor stimulant.(Both a1 and a2)
• Uses:
1. Mostly used as a local vasoconstrictor for the relief of nasal congestion due to allergic or infarction
manifestations.
2. It is also employed as an ophthalmic solution for the relief of ocular congestion(swollen eyelids and eyes
sensitive to bright light).
• Storage:
 It should be stored in well-closed airtight containers, protected from light.
• Dose:
 For nasal mucosa, 2 drops of 0.05% solution; for conjunctivitis, 1 to
2 drops of a 0.1% solution after every 3 to 4 hours.

60. Naphazoline

61. 13. Oxymethazoline
 It is a direct acting sympathomimetic drug. Chemically it is 3-(4,5-dihydroxy-
1-imidazol-2- methyl)- 2,4-Dimethyl-6-tert-butyl Phenol.
• Chemical Formula: C16H24N20
• Molecular Weight: 260.37456 g/mol
• Mechanism of action:
 It bind with both a1 and selective a2 Receptor. (It stimulates the blood vessels
of nose)
• Uses:
1. It act as a decongestant during the allergy or infection of the nasal passage.
• Dose:
 By intranasal, 1 drop of a 0.1% solution in adult, or a spray of 0.05% solution.

62. Oxymethazoline

63. 14. Xylomethazoline
 It is a direct acting sympathomimetic drug.
 Chemically it is 2-[(4-tert-butyl-2,6-dimethyl phenyl)methyl]-4,5 dihydro-IH-
imidazole.
• Molecular Formula: C16H24N2
• Molecular Weight: 244.37 g/mol
• Mechanism of action:
 It is partially agonist at a2 and selective agonist at a1 Receptor.
• Dose:
 By intranasal, 1 drop of a 0.1% solution in adult; or a spray of
0.05% solution.
• Uses:
1. Act as a vasoconstrictor, when applied topically to mucous membranes
particularly.
2. It is frequently employed as a local vaso-constrictor for nasal congestion caused
by sinusitis or rhinitis.(Otrivin)

64. Xylomethazoline

65. Indirect acting drugs :-
 The indirect-acting drugs do not bind to specific receptors, but act by releasing
stored norepinephrine. This means that their actions are non specific

66. 1.Hydroxyamphetamine
 Hydroxyamphetamine is indirect acting sympathomimetic agents and derivatives
of Amphetamines.
 It is chemically 4-(2-amino propyl)Phenol.
• Chemical formula: C9H13NO
• Mol. Mass: 151.206 g/mol
• Properties: It is a white powder freely soluble in water.
• Mechanism of action:
Indirectly acting sympathomimetics agent which causes the release of norepinephrine
from adrenergic nerve terminals.
• Uses:
1. It is a sympathomimetic and anticholinergic combination and relaxes muscles of
the eye by dilating the pupil(mydriasis).
2. It act an anorexiant(Drug that act on the brain to suppress appetite) in the
treatment of obesity

67. Hydroxyamphetamin
e

68. 2. Pseudoephedrine
 It is an optically active isomer of Ephidrine.
• Chemical formula: C10H15NO
• Mechanism of action :
 It is stimulates both a and ẞ receptors.
 It stimulates CNS.
• Uses:
1. It is used as vasoconstrictor to treat nasal and sinus congestion of tubes that
drain fluid from your inner ears.
2. It increases the blood pressure(Hypertension) by increasing cardiac output
and by causing vasoconstrictor.

69. Pseudoephedrine

70. 3. Propylhexedrine
 It is chemically (+)- 1- cyclohexyl-N-methypropan-2-amine.
• Chemical formula: C10H2IN
• Mol. Mass: 155.29 g/mol
• Mechanism of action:
 It is stimulates a-receptors in the mucosa of respiratory tract. Same action
shown as epinephrine and nor-epinephrine.
• Uses:
1. It is used for the relief of congestion due to cold, allergies and allergic
rhinitis(Inflammation of mucous membrane of nose) .

71. Propylhexedrine

72. Mixed acting drugs :-
Drugs that indirectly release NE and also directly activate receptors are referred to
as mixed-acting sympathomimetic drugs

73. 1.Ephedrine
 It is chemically 4-(2-amino propyl)Phenol.
 It occurs naturally.
 It has two asymmetric carbon atoms, so it has four isomers.
• Chemical formula: C10H15NO
• Mol. Mass: 165.24 g/mol
• Mechanism of action:
 It act both directly and Indirectly.
 It stimulates both a and ẞ receptor.
• Uses:
1. Used as bronchodialator, orthostatic hypotension(condition in which your
blood quickly drops when you stand up from a sitting or lying position).
2. It used in various allergic disease like hay fever (an allergic reaction to
pollen) and urticaria (A skin rash triggered by a reaction to food, medicine or
other irritants)

74. Ephedrine

75. 2. Metaraminol
 Chemically it is 3-(-2-amino-1-hydroxy-propyl) phenol.
• Chemical formula: C9H13NO3
• Mol. Mass: 167.205 g/mol
• Properties:
 White crystalline powder and freely Soluble in water.
• Mechanism of action:
 It act on both a and ẞ receptor stimulates noradrenaline
Uses:
1. Used parenterally as vasopressor in prevention of acute hypertension state
occurring with spinal anaesthesia.

76. Metaraminol

77. Best way to lose your weight :-
https://www.digistore24.com/redir/311818
/AFFILIATE/CAMPAIGNKEY

78. Thank youu !!