different tobacco species

1. 1
University of sulaimani
College of pharmacy
Department of pharmacognosy and pharmaceutical
chemistry
A review on
Nicotine content in different tobacco species
Prepared by
Muhammad Koksh Sdiq
B.Sc. in pharmacy

2. 2
Contents
 Introduction ……………………3
 Literature review ……………...4
 Structural identification ……….5
 Biosynthesis …………………….6
 Metabolism and elimination …….7
 Physicochemical properties ………..8
 Process of extraction …………………8
 Pharmacology ……………….9, 10
 Wiwhdrawal and toxicity…………………….11
 Discussion ………………………12
 References ………………………...13

3. 3
Introduction
Nicotine is a CNS stimulant and one of the few naturally occurring
liquid alkaloids, obtained from the tobacco plant (Nicotiana spp). It’s
pharmacological actions are complex and include effects on both the
central and peripheral nervous system. Nicotine is classified as a
stimulant of autonomic ganglia, although it possesses both stimulant and
depressant actions. Nicotine is the active ingredient and addictive
component in tobacco smoke. Addiction is physiological and
psychological and many smokers find it difficult to stop, even when they
have illnesses which are made worse by smoking. It may be
administered during the withdrawal period in the form of transdermal
patches or chewing gum. its inherent toxicity has been used in the
control of insects. The commercial preparation of the plant involves
drying the leaves for the production of chewing tobacco, cigars,
cigarettes, and snuff. Nicotine is easily isolated from the plant for use in
nicotine replacement products (gum, patches, and nasal spray)..They're
bitter-tasting, often poisonous substances that are made by plants to
discourage animals from eating them. But many persons ignore the risk
factor of it and use them for pleasure. There are many plants from which
nicotine can be obtained. These plants are a part of the nightshade family
(include eggplant, tomato, potato, green pepper) but concentration is
quite low.
Chronic use of nicotine may cause psychologic and physical
dependence.

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Aim
 To provide the information about the botany of nicotine in different tobacco
species .
 To know the pharmacological activity and toxicity of the nicotine .
Literature review
Plant contain nicotine :
# nicotiana tabacum contain 0.6 to 0.9 % nicotine . one cigar contain 10mg
nicotine and only 2mg delivered to smokers.(2)also contain ( nornicotine ,
anabasine , nicotinic acid and nicotine amine ) (1)
Plant part used :
# dried leaves
Family :
Solanaceae
Plant contain nicotine Nicotine ng/g Amout of vegetable to obtain 1
microgram nicotine by g .
Cauliflower 3.8 263.4
Eggplant 100 10
Potatoes 7.1 140.4
Tomatoes 4.1 244
Green tomato 42.8 23.4

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Table 1 (plant containing nicotine)(1)
Structure identification
Figure -1- (-)- nicotine (3)
Nicotine is also called 3-(1-methyl-2-pyrrolidinyl)pyridine according to the
IUPACa nomenclature. It is a bicyclic compound with a pyridine cycle and a
pyrrolidine cycle. The molecule possesses an asymmetric carbon and so exists in
two enantiomeric compounds. In nature, nicotine only exists in the S shape, which
is levoisomer.
 basic compound
 water soluble
 lipophilic
 environments:
o no absorption in acidic environments
o functions at blood pH = 7.4 (31%)
o absorption occurs readily in basic environments

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Biosynthesis
Figure -2- nicotine biosynthesis (4)
 nicotine contain both pyridine and pyrollidine nucleus .
 derived from L- ornithine and L- Aspartate .

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Metabolism & elimination
Figure -3- metabolic pathway of nicotine (5)
The presence of nicotine and its metabolite cotinine in the body fluids of
nonsmokers is usually taken as evidence of exposure to environmental tobacco
smoke. Recently, the Centers for Disease Control and Prevention studied 800
people, both smokers and nonsmokers, all of whom tested positive for urinary
cotinine .
Eliminated mainly by kidney via urine also by Hepatic, Pulmonary.

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Physicochemical properties
1) Nicotine is an oily liquid that is colorless to pale yellow.
2) Very hygroscopic and turns brown on exposure to air or light.
3) When nicotine is mixed with water, it's volume contracts.
4) Nicotine forms salts with almost any acid and double salts with many metals
and acids.
5) Nicotine is very soluble in alcohol, chloroform, ether, petrolatum ether,
kerosene and oils.(6)
Process of extraction
 6gm of tobacco + Ba(OH)2 ( powder + liquid)
Add 100ml toluene
After 20 min filtration
 Use burrete with standerezed 0.1M HClO4
 Add 4-5 drops of crystal violet
Titration
Greenish yellow end point .
Figure -4- extraction of nicotine

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Pharmacology
 The nicotine molecules attach to the nicotinic acetylcholine receptors on
ganglionic site of SANS and PSANS and CNS.
 The nerve cells respond to the nicotine molecules by releasing the
neurotransmitter glutamate.
 The glutamate alerts neurons to release dopamine
Result: Pleasurable feelings, stress reduction, increased heart
rate, heightened alertness, increased ability to process information, and
improved cognitive abilities.
 Enhance secretion of adrenaline and noradrenaline by adrenal medulla so
increase heart rate , peripheral vascular resistant so elevate blood pressure .
 In chronic use affect the kidney may lead to renal failure , tachycardia ,
possibility to cause heart failure due to increase workload on the heart .
 affect nicotinic receptor in GIT resemble the action of Ach , it cause diarrhea
by increasing peristalsis movement and tone of smooth muscle .also increase
secretion of digestive fluid in GIT .
 At low dose stimulate CNS by increasing transmission in CNS . while at
high dosecause depressionof CNS , also depress respiratory center in CNS .
 At low dose activate vagal nerve so decrease HR , but at high dose increase
secretion of adrenaline lead to tachycardia .
 adrenaline also affect metabolism of fat so increase LDL conc. In blood and
increase risk of atherosclerosis and MI.
 incomplete combustion of nicotine lead to formation of carcinogenic
substance ( nitrosamine ) that directly attack DNA , mainly produce lung
cancer .
 heavy smoker less subject to Alzheimer disease .

10. 10
Positive effect
 Anxiolysis , Cognitive Enhancement , Cerebro-vasodilation ,
Neuroprotection ,Analgesia, Anti-psychotic .
Negative effect
 Gastrointestinal Distress , Hypothermia , Emesis , Hypertension , Seizures ,
Respiratory Distress .
Addictive Nature
 Nicotine is highly addictive and is actually comparable to other hard drugs
such as cocaine and heroin in its addictiveness.
 Due to nicotine’s ability to promote the release of dopamine, smokers
become dependent on nicotine to help release dopamine, and must have
increasingly more to produce the same effect.
 Nicotine takes effect in the limbic system of the brain which contains the
brain’s natural “reward system” which alerts a person that something is
good and that they should continue doing it . (4)
What Age-Groups Smoke The Most ?
Age Men Women
18-24 37.2 18.9
25-34 34.2 29.5
35-44 34.8 21.5
45-54 31.9 13.4
55-64 17.0 18.1
65 & over 12.0 19.2
Table-2- The percentage of smokers by age group (7)

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Withdraw
 Many smokers experience an increase in their stress level between each
cigarette, which is relieved when they next smoke.
 Symptoms experienced by abstaining from smoking: increased anxiety,
irritability, poor concentration, restlessness, and trouble sleeping
Toxicity
 Even a small drop of nicotine in its pure form would be enough to kill
someone. This toxicity gives it the potential to be used as a pesticide.
 Smoking cigarettes, which is the main method of nicotine use, is linked to
various illnesses, such as: cancer of the upper and lower respiratory tract,
chronic obstructive pulmonary disease (COPD), heart disease
 Symptoms of nicotine toxicity, otherwise known as acute nicotine poisoning,
include nausea, vomiting, salivation, pallor, abdominal pain, diarrhea, and
cold sweat.(8)

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Discussion
Nicotine present in different tobacco species also in some plants. While many
people were enjoying the use of tobacco, others were beginning to think that it
might not be as healthful as had once been thought. Although at this time people
generally did not contest the medicinal value of tobacco, some began to suspect
that tobacco produced negative effects as well . Nicotine has an extremely short
half life. That's to say, once inside the body it breaks down pretty quickly. And that
affects how frequently people smoke. And because nicotine is so addictive so you
only need to try a few of these cigarettes or any type of nicotine to become
addicted to it - that's a major concern. So it is good that the industry is looking for a
safer cigarette, because at the moment they say that low-nicotine, low-tar cigarettes
are safer. But what actually happens is they sell more cigarettes because people
obviously puff harder and smoke more of them to get their same dose of nicotine.
So that's actually a good commercial strategy. Nicotine is primarily indicated in
conditions like Tobacco withdrawal. Nicotine should be used with caution in
patients with history of heart disease, high blood pressure, cerebrovascular disease,
endocrine disorders including hyperthyroidism and insulin-dependent diabetes,
peptic ulcer, impaired liver or kidney function. Skin patches should not be used on
broken skin. This is not recommended for use during pregnancy or lactation.The
hope for the future is that drug companies will be able to separate nicotine's
positive properties from the negative and develop drugs for the treatment of
everything from Alzheimer's disease to weight control.
Educate patients about the benefits of smoking cessation and the cessation
process. Provide a description of the expected withdrawal syndrome. Continue
with a discussion of the possible cessation methods, which include counseling,
nicotine replacement, antidepressant medications, behavioral training, group
therapy, hypnosis.

13. 13
References
1) Siegmund B, Leitner E, Pfannhauser W (1999) Determination of the nicotine content of
variousedible nightshades (Solanaceae) and their products and estimation of the associated
dietary nicotine intake. J Agric Food Chem 47(8):3113–3120 .
2) Benowitz NL, Jacob P 3rd (1984) Daily intake of nicotine during cigarette smoking. Clin
Pharma-col Ther 35(4):499–504 .
3) http://examine.com/supplements/Nicotine/
4) Yang KS, Gholson RK, Waller GR (1965) Studies on nicotine biosynthesis. J Am Chem
Soc87: 4184–4188 .
5) Edward F. Domino(1999). Pharmacological significance of nicotine. In: Analytical
Determination of Nicotine and Related Compounds and their Metabolites. Elsevier, :1-11 .
6) http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=89594
7) Perry, M. (2006, August 18). Understanding nicotine dependence. Practice Nurse, 39-43.
8) André Conrad 2011. Exposure to Tobacco Smoke. In: Cigarette Smoke Toxicity. Wiley-VCH
Verlag GmbH & Co. KGaA:67-91.