Atropine

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.

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 g enera. 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 C 17 H 23 NO 3 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 o C Boiling Point: 393 o C 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 ” ( C 17 H 23 NO 3 ) 2 · H 2 SO 4 ·H 2 O Full chemical name 1 α H , 5 α 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 H 2 SO 4 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

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17. BIO SYNTHESIS 10/30/2018 17

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 " , K ing 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

22. THANK YOU 10/30/2018 22