Ephedrine (Alkaloid)

CNS stimulant

1. Ephedrine MADISH NIAZ BS CHEMISRTY

2. Hi s tory: Also known as Ma- Huang Ephedra has been used as medicine for over 60,000 years Used in Chinese medicine for more than 5,000 years Originally prescribed to treat asthma congestion allergies

3. CHEMIAL STRUCTURE:   Chemical Formula: C 10 H 15 NO Molecular Weight: 165.23 grams/mole Melting Point: 37-39°C Boiling Point: 253-255°C Brand  names : Akovaz , Corphedra . Drug class(es): Decongestants vasopressors EPHEDRINE

4. IUPAC NAME: The IUPAC names of the two enantiomers are (1 R ,2 S ) -2-methylamino-1-phenylpropan-1-ol (1 S ,2 R )-2-methylamino-1-phenylpropan-1-ol. A synonym is  erythro -ephedrine.

5. Ephedrine exhibits  optical isomerism and has two  chiral centres , giving rise to four  stereoisomers STRUCTURAL ELLUCIDATION:

6. STRUCTURAL COMPARISON: Ephedrine is a  substituted amphetamine  and a structural  methamphetamine  analogue. In the outdated  D/L system  (+)-ephedrine is also referred to as L-ephedrine and (−)-ephedrine as D-ephedrine

7. CHEMISTRY: Chemically, it is an alkaloid with a phenethylamine skeleton found in various plants in the genus  Ephedra  (family  Ephedraceae ). Ephedra consists of the dried aerial parts of Ephedra gerardiana , Ephedra sinica , Ephedra equisetina other Ephedra species. It is most usually marketed as the hydrochloride or sulfate salt.

8. APPEARANCE: White crystalline powder Bitter taste Soluble in water Very soluble in alcohol

9. MECHANISM OF ACTION: It works mainly by increasing the activity of norepinephrine (noradrenaline) on adrenergic receptors. On the surface of fat and muscle cells there are b-receptors B-receptors bind with b-agonists (adrenaline) causing chemical reactions that produce the chemical messenger C- AMP C-AMP activates enzymes which induce lipolysis (fat breakdown) in fat cells and increase metabolism in muscle cells. In supplements containing the ephedrine-caffeine-aspirin mix, ephedrine enhances b-agonist production. Caffeine inhibits the breakdown of C-AMP. Aspirin inhibits the reduction of b-agonist production.

10. Extraction:

11. SYNTHESIS: Ephedrine can be synthesized from benzaldehyde in a few different ways. According to the first, benzaldehyde is condensed with nitroethane, giving 2-methyl-2-nitro-1-phenylethanol , which is reduced to 2-methyl-2-amino-1-phenylethanol . The necessary L-isomer is isolated from the mixture of isomers by crystallization. Methylation of this gives ephedrine.

12. SYNTHESIS: The second method consists of the fermentation of glucose by yeast carboligase in the presence of benzaldehyde , which during the process turns into phenylacetylcarbinol . This is reduced by hydrogen in the presence of methylamine to give the desired ephedrine.

13. BIOSYNTHESIS OF EPHEDRINE: Biosynthesis of ephedrine by ephedra begins with L-phenylalanine ( Phe ). Phenylalanine is the initial precursor of ephedrine and pseudoephedrine and catalyzed by phenylalanine ammonia lyase (PAL )

14. BIOSYNTHESIS OF EPHEDRINE: Phenylalanine first forms cinnamoyl-CoA via the enzymes phenylalanine ammonia-lyase and acyl CoA ligase.

15. BIOSYNTHESIS OF EPHEDRINE: The cinnamoyl-CoA is then reacted with a hydratase to attach the alcohol functional group. The product is then reacted with a retro-aldolase, forming benzaldehyde benzalde h yde Cinnamoyl-CoA

16. BIOSYNTHESIS OF EPHEDRINE: Benzaldehyde undergo dehydrogenase to form benzoic acid. After undergoing condensation with pyruvate to form 1-phenylpropane-1,2-dione this reaction catalyzed by a ThDP -dependent carboligase .Transamination of 1-Phenylpropane-1,2-dione yields cathinone.

17. Then cathinone is reduced to norephedrine. In the end, N-Methylation to form ephedrine. BIOSYNTHESIS OF EPHEDRINE:

18. MEDICINAL USES:

19. USE IN WEIGHT LOSS: Increases fat loss. Maintains muscle mass. Prevents the fall of HDL cholesterol during weight loss. Increases insulin sensitivity. Reduces lipogenesis (the conversion of carbohydrates to fat).

20. USED AS BODY BUILDING AIDS: Ephedrine has also been used by athletes who believe it makes them stronger or have more energy and endurance.

21. AS A NUTRITIONAL SUPPLEMENT: It not only has thermogenic and lipolytic characteristics but also used as a nutritional supplement. Users have lost weight and gained strength in prolonged use of Ephedrine. It is also called a performance-enhancing pill as it gives an instant energy boost to athletes upon taking it.

22. Benefits of Modern Ephedrine Use: Maintains levels of HDL cholesterol May reduce the risk of cardiovascular disease No signs of long term toxicity May increase life expectancy in women It is used to increase urine flow in people who retain fluids.

23. Side Effects: Abnormally high blood pressure Rapid, irregular heartbeat Anxiety Dizziness Insomnia Tremor Rapid pulse Sweating Respiratory difficulties Confusion Hallucinations Delirium Convulsions.

24. Individual Cases: The New England Journal of medicine links at least 54 deaths to ephedrine Since 1994 the FDA has had over 800 reported cases of side effects from ephedrine. 273 resulted in death Death of NFL player Korey Stringer tied to ephedrine use. Numerous college athlete deaths also linked Athletic deaths linked to ephedrine result from rise in body temperature

25. Conclu s ion: Ephedrine should be used intelligently and with caution Consult a doctor before starting s u p p l e me n ta t i o n

26. THANK YOU