This document discusses alkaloids and nicotine. It provides details on the historical awareness of tobacco, forms of tobacco, biosynthesis and extraction of nicotine. It describes the pharmacokinetics and pharmacodynamics of nicotine, including its physiological effects. Determinants of tobacco use and various treatment options are also outlined.

1. Alkaloids
prepared by Sonia knawel
Nicotine

2. contents
 ALKALOIDS
 NICOTINE
 Historical Awareness
 Forms 0f tobacco
 Common Food with Nicotine Content
 Biosynthesis of nicotine
 Extraction of nicotine
 structure elucidation
 Pharmacokinetics
 Pharmacodynamics
 Determinants of Tobacco Use
 Treatment options

3. ALKALOIDS
 Alkaloid, are naturally occurring organic nitrogen-
containing bases.
 Alkaloids have divers and important physiological
effects on humans and other animals.
 Well-known alkaloids include morphine, quinine,
ephedrine, and nicotine.
 Alkaloids are found primarily in plants and are
especially common in certain families of flowering
plants. More than 3,000 different types of alkaloids
have been identified in a total of more than
4,000 plant species.
https://www.britannica.com/science/alkaloid

4.  Both opium poppy and fungus argot contain about
30 different types of alkaloids
All Parts e.g. Datura.
Barks e.g. Cinchona
Seeds e.g. Nux vomica
Roots e.g. Aconite
Fruits e.g. Black pepper
Leaves e.g. Tobacco
Latex e.g. Opium
Distribution in Plant:

5. NICOTINE
• Nicotine is soluble in water and in non polar
solvents.
•Nicotine is an pyridine pyrrolidine alkaloid found naturally
in tobacco plants, constitutes aproximately 0.6- 3.0 percen
of dry weight of tobacco
•Ncotiana tabacum, the type of nicotine
found in tobacco plants, comes from the
nightshade family(solanaceae).
Nicotine is a brown liquid and Volatile in nature
https://en.wikipedia.org/wiki/Nicotine

6. Nicotine is synthesized in the roots of tobacco plants and
it is then carried to the leaves, where it is stored in
concentrations of between 2 to 8 percent by weigh.
nicotine is also an antiherbivore chemical, specifically for
the elimination of insects - it extensively used as an
insecticide. "
Nicotine is as addictive as heroin
Causes physical dependence
Highly hydrophobic, so can cross blood brain barrier.
http://www.encyclopedia.com/science-and-technology/chemistry/organic-chem/nicotine

7. Historical Awareness
1560 - Marked as 1st yr tobacco
officially introduced to Europe
Proponents of tobacco
Sir Francis Drake
Sir Walter Raleigh
Led to the fashionability of pipe
smoking of tobacco
2, 000 years ago (maybe 6,000) - natives of the
Americas used tobacco as a medicine, in religious
ceremonies, and as offerings to spirits.
1492 - Christopher Columbus introduce tobacco and
nicotine to Spain
http://www.toxipedia.org/download/attachments/6003685/Chpater%206%20Slides%2

8. 1612 - British colony at Jamestown, Virginia,
exporting tobacco to England – became an
essential source of money
1700-1800’s - Farms used slaves to cultivate
tobacco
Historical Awareness
1828 - Nicotine was isolated from the tobacco plant by
German chemists posselet and Reimann
formally introduced to Europe as a medicinal herb
over 60 species of nicotiana but only 2 major ones;
1850s, Cigarettes first appeared , but chewing
still more popular

9. Forms 0f tobacco
smokebal tobacco
cigar or pipes
Tight rolls of tobacco leaves.
Flue-curing - process of
heating tobacco leaves to cure
them, make a milder smoke.
Cigarettes
Rolls of shredded tobacco wrapped in
paper
The smoke is
than drawn through the stem and
mouthpiece and inhaled. Pipes are often
reusable
Pipe smoking has been shown to cause
gum disease and tooth loss,
is a pipe used to smoke Shisha,
a combination of tobacco and
fruit or vegetable that is heated
and the smoke is filtrated
through water.
The tobacco or Shisha is
heated in the hookah usually
using charcoal.
Hookah
• www.ct.gov/dph/lib/dph/hems/tobacco/tobacco_products.pdf

10. snuff
Grind tobacco into fine
powder
•Pinch into nose & exhale with sneeze.
• Started in France & spread through rest
of Europe
In U.S., snuffing replaced by chewing
Free hands for working
Low cost -
Chewing
The two main types of smokeless tobacco
are
chewing tobacco and snuff.
Chewing tobacco comes in the form of
loose leaf, plug, or twist
Smokeless tobacco

11. Common Food with Nicotine Content
few common vegetables and plants, mostly from the
Solanaceae (nightshade) family, shown to have nicotine
content.
Tomato
belongs to the solanaceae family ,found to posses a
nicotine alkaloid called tomatine
It has an average of 7.1- 7.3 ng/g wet weight. It means
there is a 7.1 ng of nicotine in every 1 gram of tomato
Potato
Potatoes also contain a nicotine alkaloid called solanine,
which is highly concentrated on its skin.
abouttesting.testcountry.com/.../6-common-food-with-nicotine-content.h

12. Eggplant
 Eggplants have a concentration of 100 ng/g ,of nicotine.
It is second highest next to tobacco among the
nightshade family where nicotine alkaloids are
commonly present.
 In simple terms, 10 kg of eggplant have the same
nicotine content as stick of cigarette.
Tea
 green and black teas also contain small amounts of
nicotine whether regular or decaffeinated
Common Food with Nicotine Content

13. Cauliflower is another food source of nicotine. The nicotine
concentration contained in cauliflower is 16.8 ng/g.
 cauliflower is also an excellent dietary source of vitamin K
,vitamin C, and fiber.
 Regular consumption of cauliflower will promote some health
benefits such as protection against some forms of cancer,
detoxification in the body
Peppers and Capsicums.
 Peppers and capsicums also contain solanine and solanadine,
nicotine alkaloids, just like the other nightshade family plants.
Common peppers have a solanine concentration of 7.7 – 9.2 mg
per 100 grams of serving
Cauliflower

14. Biosynthesis of nicotine
The biosynthetic pathway of nicotine involves a coupling
reaction between the two cyclic structures that compose
nicotine.
Metabolic studies show that the pyridine
ring of nicotine is derived from niacin(nicotinic acid) while
the pyrollidine is derived from N-methyl pyrrollidium cat
ion
Biosynthesis of the two component structures proceeds
via two independent syntheses
,
the NAD pathway for niacin and the tropane pathway
for N-methyl--pyrrollidium cation

15. The NAD pathway in the genus nicotiana begins with the
oxidation of aspartic acid into α-imino succinate by
aspartate oxidase (AO).
This is followed by a condensation with glyceraldehyde-
3-phosphate and a cyclization catalyzed by quinolinate
synthas (QS) to give quinolinic acid.
Quinolinic acid then reacts with Phosphoribosyl
pyrophosphate catalyzed by quinolinic acid
phosphoribosyl transferase (QPT) to form niacin
mononucleotide (NaMN).
The reaction now proceeds via the NAD salvage cycle to
produce niacin via the conversion of nicotinamide by the
enzyme nicotinamidase

16. The N-methyl--pyrrollidium cation used in the synthesis of
nicotine is an intermediate in the synthesis of tropane-
derived alkaloids.
Biosynthesis begins with decarboxylation of ornithine by
ornithine decarboxylase (ODC) to produce putrescine.
Putrescine is then converted into N-methyl putrescine
via methylation by SAM catalyzed by putrescine N-
methyltransferase (PMT).
N-methylputrescine then undergoes deamination into 4-
methylaminobutanal
by the N-methylputrescine oxidase (MPO) enzyme, 4-
methylaminobutanal then spontaneously cyclize into N-
methyl--pyrrollidium cation

17. The final step in the synthesis of nicotine is the coupling
between N-methyl--pyrrollidium cation and niacin
Although studies conclude some form of coupling
between the two component structures, the definite
process and mechanism remains undetermined.
The current agreed theory involves the conversion of
niacin into 2,5-dihydropyridine through 3,6-
dihydronicotinic acid.
The 2,5-dihydropyridine intermediate would then react
with N-methyl-pyrrollidium cation to form
enantiomerically pure (–)-nicotine.

19. Extraction of nicotine from tobacco
leavesSolvent extraction
 10 gm of tobacco leaves were dipped in 100ml of NaoH
 Solution was stirred and filter.
 Then filtrate was diluted in 30ml of distilled water filter the
solution again to remove impurities
 solution was transfer into the separating funnel and
extracted with 25ml ether.
 extraction was repeated for 3 times.
 Ether was evaporate on water bath (avoid extra heat
because nicotine is hydrolyzed by extra heating )
 After that nicotine oil is obtained
 Nicotine is liquid that is miscible in water.
 Nicotine form salt with acids that are usually solid and
water soluble.

20. steam distillation.
 Plant material + water + Fixed alkali
Heat
steam contain
alkaloids received in
acidic solution.

21. structure elucidation
Infra red spectrum of nicotine
http://www.chm.bris.ac.uk/motm/nicotine/E-propriete.html

22. pnmr spectra of nicotine

23. C-13 spectrum of nicotine

24. Mass spectrum of nicotine

25. Smoking
Nicotine in a cigarette – 8 to 10 mg
Smoking – delivers about 1 mg to the smoker
Technique of smoker can increase nicotine in Lungs
(nicotine enters brain in 7 seconds)
Skin; (slower absorption, more constant blood levels)
Stomach poor; (nicotine is strong base – stomach is acid)
Intestine better.
Cigarettes were invented by beggars in Seville,
Spain (from scrap of cigars

26. Pharmacokinetics
 Readily absorbed from all
over the body, including
 Lungs (smoked)
 Mucosa (cigar, chewing
tobacco)
 Skin (patch)
 Gastrointestinal tract
(uncommon)
Pharmacokinetics refers to what the body does to a substance

27. Nicotine Absorption
The most common way to get nicotine into your
bloodstream is through inhalation
Your lungs are lined by millions of alveoli, which are
the tiny air sacs where gas exchange occurs
These alveoli provide an enormous surface area,
90 times greater than that of your skin, and thus
provide ample access for nicotine and other
compounds
Nicotine taken in by cigarette or cigar smoking
takes only 10-15 seconds to reach the brain but
has a direct effect on the body for only ~30 minutes

28. It can be absorbed by the body from smoke that has
been taken into the lungs, or through the skin.
 It rapidly crosses the blood-brain barrier, appearing
in brain tissue; minutes after its absorption into
capillaries lining the alveoli of the lungs.
 The presence of nicotine in the body stimulates
nicotinic-cholinergic receptors of the nervous system,
resulting in increased attention span, increased heart
rate and blood pressure, and increases in the
concentrations of some hormones.

29. Metabolism & Elimination
About 80 percent of nicotine is broken down to cotinine
by enzymes in your liver
Nicotine is also metabolized in your lungs to cotinine
and nicotine-N-oxide Cotinine .
and the remaining nicotine is filtered from the blood by
your kidneys and excreted in the urine

30. Pharmacodynamics
 Nicotine is a direct agonist for
nicotinic ACh receptors
 Nicotine initially causes a rapid
release of adrenaline, the "fight-
or-flight“hormone
by binding with nAch resepter
nicotine increse the level of
several neurotransmeters
pharmacodynamics refers to what a substance does to the body.

31. Pharmacodynamics
 nAChRs found in limbic system(hypothallamus) , midbrain
, various cortical areas (frontal lobes)
 Nicotine also increases release of various neuro
hormones
 Has powerful effects on peripheral nervous system, heart,
and other organs

32. Physiological effects
in large doses, nicotine is highly toxic
 Symptoms of nicotine poisoning are Sweating ,vomiting,
mental confusion, diminished pulse rate, and breathing
difficulty ,Respiratory failure
Stimulus effect - release of norepinephrine
 Norepinephrine Iworks by constricting (narrowing) the blood
vessels and increasing blood pressure and blood glucose (sugar)
level.
 nicotine mood altering effects are different by report it is
both a stimulant and relaxent.
 first causing a release of glucose from the liver and
epinephrine (aderaline) from the adrenal meduula it
cause stimulation user report feeling of relaxation .
 By reducing the appetite and raising the metabolism
some smoker may lose weight as a consequence.
 Depression - caused by blocked nerve activity

33. Nicotine effects
 Constricts blood vessels in skin, producing cold, thin,
wrinkles (faster aging).
 Inhibits stomach secretions, stimulates bowel (laxative in
nontolerant person).
 May increase metabolism of fat; dull taste buds.
 Slows stomach contractions; increases blood sugar.
 May improve attention/memory; although high doses
may increase nervousness, seizures, panic attack.
 May have an antidepressant effect (i.e., are smokers
self-medicating?).

34. cancer
 Cancer related to nicotine include
 Mouth kidney
 Larynx bladder
 Esophagus throat
 Stomach lungs
 pancreas

35. Determinants of Tobacco Use
 Socioeconomic status
 Cultural characteristics
 Biological elements
 Stress
 Advertising (for and against)
 Price of tobacco products
 Peer pressure

36. Why should I treat tobacco use
?
 I in 5 deaths in the US are due to smoking
 1 in 3 cancer deaths are caused by smoking
 70% of smoker want to quit
 64% of New Yorkers who smoke tried to quit;
NYCommunity Health Survey 2001
 Less than 10% succeed without assistance
•A 35-year-old male who smokes two packs a day has a
life expectancy that is 8.1 years shorter than his
nonsmoking counterpart
•Based on data collected in the late 1990s, the US
Centers for Disease Control and Prevention (CDC)
estimated that adult male smokers lost an average of
13.2 years of life and female smokers lost 14.5 years of
life because of smoking.

37. Treatment options
Behavior modification
Nicotine lozenges
Nicotine gum
Nicotine patches
Nicotine inhaler
Nicotine nasal spray
Bupropion (non-nicotinic
pharmacological agent)
NRT (nicotine replacement
therapy)
• https://aidsetc.org/sites/default/files/resources_files/nynj_nicotine

38. •Zyban (buproprion) – approved
in 1997 for smoking cessation
•originally an antidepressant.
•weak inhibitor of dopamine
(Dopamine is a neurotransmitter that
helps control the brain's reward and
pleasure centers regulate movement and
emotional responses),
• and nor adrenaline reuptake,
and has also been shown to
antagonize nicotinic acetylcholine
receptor function.