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ATROPINE
NATURAL PRODUCTS
By – P.Bonehoeffer & m.ifham
10/30/2018 1
CONTENTS
• INRODUCTION
• NATURAL SOURCES
• STRUCTURE AND PROPERTIES
• CHEMISTRY AND PHARMACOLOGY
• APPLICATIONS
• LABORAORY SYNTHESIS
• BIO SYNTHESIS
• ISOLATION
10/30/2018 2
INTRODUCTION
• “Atropine” is a tropane alkaloid extracted from
Deadly nightshade (Atropa belladonna),
Jimsonweed (Datura stramonium),
Mandrake (Mandragora officinarum) and other
plants of the family Solanaceae.
• It is a Secondary metabolite of these plants and
serves as a drug with a wide variety of effects.
• Competitive antagonist for the muscarinic
acetylcholine receptor.
• Classified as an anti cholinergic drug.10/30/2018 3
• Atropine is a core medicine in the World
Health Organization's (WHO) "Essential
Drugs List", which is a list of minimum
medical needs for a basic health care system.
• Other names of Atropine…..
* dl-hyoscyamine
* (±)-hyoscyamine,
* Tropic acid ester with tropine
* Tropine (±)tropate
* dl-tropyl tropate
* (±) tropyl tropate
10/30/2018 4
Natural sources
• Atropine is found in many
members of the Solanaceae
family.
• The most commonly-found
sources are
Atropa belladonna,
Datura inoxia, D.metel
and D. stramonium.
• Other sources include
members of the
Brugmansia and
Hyoscyamus genera.
10/30/2018 5
STRUCTURE AND PROPERTIES
• Systematic (IUPAC) name
(8 - methyl - 8 - azabicyclo [ 3.2.1 ] oct - 3 - yl ) 3 -
hydroxyl - 2 - phenyl propanoate
• Molecular formula
C17H23NO3
• Molar mass
289.38 g mol-1
10/30/2018 6
Physical properties
• Solubility: Low solubility in water, 1
gram Atropine dissolves per 2 ml of
alcohol.
• Physical state: White crystals or white
crystalline powder, odorless and has a
sharp bitter taste.
• Melting Point: 114-116 oC
• Boiling Point: 393 oC
10/30/2018 7
CHEMISTRY AND
PHARMACOLOGY
• Atropine is a racemic mixture of
D-hyoscyamine and L-hyoscyamine , with
most of its physiological effects due to
L-hyoscyamine .
10/30/2018 8
• Its pharmacological effects are due to binding to
muscarinic acetylcholine receptors.
• It is an antimuscarinic agent.
• The most common atropine compound used in
medicine is “Atropine sulfate”
( C17H23NO3 )2 · H2SO4 ·H2O
• Full chemical name
1α H , 5α H –Tropan – 3 - α ol (±) – tropate (ester) , sulfate mono hydrate
10/30/2018 9
APPLICATIONS
• Old uses: Women used to put Atropine, then
known as Belladonna, into their eyes in an
attempt to make their pupils larger.
• Current uses:
• Used as a depressant for the stimulation
of unconscious internal processes.
• A heart stimulant.
• Opposes action of the Vagus Nerve.
10/30/2018 10
Drug applications
1. Ophthalmic use
Atropine is used as a cyclo plegic, to
temporarily paralyze the accommodation
reflex, and as a mydriatic, to dilate the pupils.
2. Resuscitation
Injections of atropine are used in the treatment
of bradycardia (an extremely low heart rate),
asystole and pulseless electrical activity (PEA)
in cardiac arrest.
10/30/2018 11
3. Secretions and broncho constriction
Atropine's actions on the parasympathetic
nervous system inhibits salivary, sweat, and
mucus glands. This can be useful in treating
hyperhidrosis, and can prevent the death rattle
of dying patients.
4. Treatment for organo phosphate poisoning
Atropine is given as a treatment for
SLUDGE (Salivation, Lacrimation, Urination,
Diaphoresis, Gastrointestinal motility,Emesis)
symptoms caused by organophosphate
poisoning .
10/30/2018 12
LABORATORY SYNTHESIS
• Atropine synthesis involves 2 major steps
1. Synthesis of Tropine
2. Synthesis of Tropic Acid
and last step is there combination to form
ultimately Atropine
The first step is Synthesis of Tropine
The immediate compound are Succinaldehyde,
methylamine and Acetone to form Tropinone,
this Tropinone upon reduction yields Tropine.
10/30/2018 13
• The second step is synthesis of Tropic Acid is
carried out via Phenyl Acetic Acid and Propyl
magnesium Chloride in the presence of ether
and intermediate product formation, followed
by subsequent treatment with H2SO4 yields
tropic acid.
The last step in this synthesis is combination of
both products i.e, Tropine + Tropic Acid to
yield Atropine by adding HCl.
10/30/2018 14
10/30/2018 15
10/30/2018 16
BIO SYNTHESIS
10/30/2018 17
ISOLATION
• Atropine is racemic form of l-hyoscyamine.
The latter can be racemised by heating with
ethanol alkaline solution
• Procedure
(1)Dry 500 g seeds of plant (D.stramoinum).
(2) Boil the seeds in water for 1-1.5 hours in a
beaker.
(3) Strain the extract through a fine pored mess.
10/30/2018 18
(4) Add 4 ml of con. Sulphuric acid into the
liquid and leave for half an hour.
(5) Take out the clear layer of liquor with the
help of a pipette.
(6) Filter to obtain a transparent sherry-coloured
solution.
(7) Add ammonium carbonate to the solution till
saturation.
(8) Find colour change of the solution to black
from sherry.
10/30/2018 19
(9) Leave to obtain crystals of atropine in
15-30 minutes.
(10) Take out the upper supernatant with the
help of a Pasteur pipette.
(11) Dry the crystals on a filter paper and
dissolve dried crystals into boiling alcohol.
(12) Evaporate alcohol and obtain pure
crystals of atropine.
10/30/2018 20
REFERENCES
• Abdullah A. Al-Badr and Farid J. Muhtadi, “ATROPINE ",
King Saud University Riyadh, Saudi Arabia (1998)
• A. Fasth, J. Sollenberg, B. Sorbo; "Production and
characterisation of antibodies t o Atropine", Acta Pharm.uec.
12, 311 (1975).
• T.Ismail., "ALKALOIDS & ALKALOIDS PLANTS" , Adana
university and joint research centre.
• R. Nath Singh, J.Kumar, D.Prasad, S.Prasad, " Extraction of
two medicinally active compounds fromplant sources “
10/30/2018 21
THANK YOU
10/30/2018 22

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Atropine

  • 1. ATROPINE NATURAL PRODUCTS By – P.Bonehoeffer & m.ifham 10/30/2018 1
  • 2. CONTENTS • INRODUCTION • NATURAL SOURCES • STRUCTURE AND PROPERTIES • CHEMISTRY AND PHARMACOLOGY • APPLICATIONS • LABORAORY SYNTHESIS • BIO SYNTHESIS • ISOLATION 10/30/2018 2
  • 3. INTRODUCTION • “Atropine” is a tropane alkaloid extracted from Deadly nightshade (Atropa belladonna), Jimsonweed (Datura stramonium), Mandrake (Mandragora officinarum) and other plants of the family Solanaceae. • It is a Secondary metabolite of these plants and serves as a drug with a wide variety of effects. • Competitive antagonist for the muscarinic acetylcholine receptor. • Classified as an anti cholinergic drug.10/30/2018 3
  • 4. • Atropine is a core medicine in the World Health Organization's (WHO) "Essential Drugs List", which is a list of minimum medical needs for a basic health care system. • Other names of Atropine….. * dl-hyoscyamine * (±)-hyoscyamine, * Tropic acid ester with tropine * Tropine (±)tropate * dl-tropyl tropate * (±) tropyl tropate 10/30/2018 4
  • 5. Natural sources • Atropine is found in many members of the Solanaceae family. • The most commonly-found sources are Atropa belladonna, Datura inoxia, D.metel and D. stramonium. • Other sources include members of the Brugmansia and Hyoscyamus genera. 10/30/2018 5
  • 6. STRUCTURE AND PROPERTIES • Systematic (IUPAC) name (8 - methyl - 8 - azabicyclo [ 3.2.1 ] oct - 3 - yl ) 3 - hydroxyl - 2 - phenyl propanoate • Molecular formula C17H23NO3 • Molar mass 289.38 g mol-1 10/30/2018 6
  • 7. Physical properties • Solubility: Low solubility in water, 1 gram Atropine dissolves per 2 ml of alcohol. • Physical state: White crystals or white crystalline powder, odorless and has a sharp bitter taste. • Melting Point: 114-116 oC • Boiling Point: 393 oC 10/30/2018 7
  • 8. CHEMISTRY AND PHARMACOLOGY • Atropine is a racemic mixture of D-hyoscyamine and L-hyoscyamine , with most of its physiological effects due to L-hyoscyamine . 10/30/2018 8
  • 9. • Its pharmacological effects are due to binding to muscarinic acetylcholine receptors. • It is an antimuscarinic agent. • The most common atropine compound used in medicine is “Atropine sulfate” ( C17H23NO3 )2 · H2SO4 ·H2O • Full chemical name 1α H , 5α H –Tropan – 3 - α ol (±) – tropate (ester) , sulfate mono hydrate 10/30/2018 9
  • 10. APPLICATIONS • Old uses: Women used to put Atropine, then known as Belladonna, into their eyes in an attempt to make their pupils larger. • Current uses: • Used as a depressant for the stimulation of unconscious internal processes. • A heart stimulant. • Opposes action of the Vagus Nerve. 10/30/2018 10
  • 11. Drug applications 1. Ophthalmic use Atropine is used as a cyclo plegic, to temporarily paralyze the accommodation reflex, and as a mydriatic, to dilate the pupils. 2. Resuscitation Injections of atropine are used in the treatment of bradycardia (an extremely low heart rate), asystole and pulseless electrical activity (PEA) in cardiac arrest. 10/30/2018 11
  • 12. 3. Secretions and broncho constriction Atropine's actions on the parasympathetic nervous system inhibits salivary, sweat, and mucus glands. This can be useful in treating hyperhidrosis, and can prevent the death rattle of dying patients. 4. Treatment for organo phosphate poisoning Atropine is given as a treatment for SLUDGE (Salivation, Lacrimation, Urination, Diaphoresis, Gastrointestinal motility,Emesis) symptoms caused by organophosphate poisoning . 10/30/2018 12
  • 13. LABORATORY SYNTHESIS • Atropine synthesis involves 2 major steps 1. Synthesis of Tropine 2. Synthesis of Tropic Acid and last step is there combination to form ultimately Atropine The first step is Synthesis of Tropine The immediate compound are Succinaldehyde, methylamine and Acetone to form Tropinone, this Tropinone upon reduction yields Tropine. 10/30/2018 13
  • 14. • The second step is synthesis of Tropic Acid is carried out via Phenyl Acetic Acid and Propyl magnesium Chloride in the presence of ether and intermediate product formation, followed by subsequent treatment with H2SO4 yields tropic acid. The last step in this synthesis is combination of both products i.e, Tropine + Tropic Acid to yield Atropine by adding HCl. 10/30/2018 14
  • 18. ISOLATION • Atropine is racemic form of l-hyoscyamine. The latter can be racemised by heating with ethanol alkaline solution • Procedure (1)Dry 500 g seeds of plant (D.stramoinum). (2) Boil the seeds in water for 1-1.5 hours in a beaker. (3) Strain the extract through a fine pored mess. 10/30/2018 18
  • 19. (4) Add 4 ml of con. Sulphuric acid into the liquid and leave for half an hour. (5) Take out the clear layer of liquor with the help of a pipette. (6) Filter to obtain a transparent sherry-coloured solution. (7) Add ammonium carbonate to the solution till saturation. (8) Find colour change of the solution to black from sherry. 10/30/2018 19
  • 20. (9) Leave to obtain crystals of atropine in 15-30 minutes. (10) Take out the upper supernatant with the help of a Pasteur pipette. (11) Dry the crystals on a filter paper and dissolve dried crystals into boiling alcohol. (12) Evaporate alcohol and obtain pure crystals of atropine. 10/30/2018 20
  • 21. REFERENCES • Abdullah A. Al-Badr and Farid J. Muhtadi, “ATROPINE ", King Saud University Riyadh, Saudi Arabia (1998) • A. Fasth, J. Sollenberg, B. Sorbo; "Production and characterisation of antibodies t o Atropine", Acta Pharm.uec. 12, 311 (1975). • T.Ismail., "ALKALOIDS & ALKALOIDS PLANTS" , Adana university and joint research centre. • R. Nath Singh, J.Kumar, D.Prasad, S.Prasad, " Extraction of two medicinally active compounds fromplant sources “ 10/30/2018 21