Nicotine

Alkaloids
prepared by Sonia knawel
 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
 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
 Both opium poppy and fungus argot contain about
30 different types of alkaloids

Distribution in Plant:
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
 NICOTINE
•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 soluble in water and in non polar

solvents.
Nicotine is a brown liquid and Volatile in nature

https://en.wikipedia.org/wiki/Nicotine
 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
 Historical Awareness

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
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
http://www.toxipedia.org/download/attachments/6003685/Chpater%206%20Slides%2
 Historical Awareness
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

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
 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.
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,
• www.ct.gov/dph/lib/dph/hems/tobacco/tobacco_products.pdf
Hookah
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.
Cigarettes
Rolls of shredded tobacco wrapped in
paper
Smokeless tobacco
The two main types of smokeless tobacco
are
chewing tobacco and snuff.

snuff
Grind tobacco into fine
powder
•Pinch into nose & exhale with sneeze.

• Started in France & spread through rest

of Europe
Chewing
Chewing tobacco comes in the form of
loose leaf, plug, or twist

In U.S., snuffing replaced by chewing

Free hands for working
Low cost -
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
 Common Food with Nicotine Content

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
 Cauliflower

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
 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
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
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
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.
 Extraction of nicotine from tobacco
leaves
Solvent 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.
 steam distillation.

 Plant material + water + Fixed alkali

Heat
steam contain
alkaloids received in
acidic solution.
 structure elucidation
Infra red spectrum of nicotine

http://www.chm.bris.ac.uk/motm/nicotine/E-propriete.html
pnmr spectra of nicotine
C-13 spectrum of nicotine
Mass spectrum of nicotine
 Smoking
Cigarettes were invented by beggars in Seville,
Spain (from scrap of cigars

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.
 Pharmacokinetics
Pharmacokinetics refers to what the body does to a substance

 Readily absorbed from all

over the body, including
 Lungs (smoked)
 Mucosa (cigar, chewing
tobacco)
 Skin (patch)
 Gastrointestinal tract
(uncommon)
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
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.
 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
Pharmacodynamics
pharmacodynamics refers to what a substance does to the body.

 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
 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
 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
 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?).
cancer
 Cancer related to nicotine include
 Mouth kidney
 Larynx bladder
 Esophagus throat
 Stomach lungs
 pancreas
Determinants of Tobacco Use
 Socioeconomic status
 Cultural characteristics
 Biological elements
 Stress
 Advertising (for and against)
 Price of tobacco products
 Peer pressure
 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.
 Treatment options
Behavior modification
NRT (nicotine replacement
therapy)
Nicotine lozenges
Nicotine gum
Nicotine patches
Nicotine inhaler
Nicotine nasal spray

Bupropion (non-nicotinic
pharmacological agent)

• https://aidsetc.org/sites/default/files/resources_files/nynj_nicotine
•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.