By Nur Sumaiyyah Lawson

1. BPH3024
NEUROPHARMACOLOGY

2. NICOTINE
NUR SUMAIYYAH LAWSON BINTI ABDULLAH
BACHELOR IN BIOMEDICINE SCIENCES

3. What is nicotine?
 Nicotine is a nitrogen-containing chemical that is an alkaloid.
It is made by several types of plants including the tobacco
plant. Nicotine can also be produced synthetically.
 Nicotine is obtained from the tobacco plant , Nicotiana
tabacum. This plant comes from the nightshade family which
has other members for example red peppers, eggplant,
tomatoes and potatoes.

4. What is nicotine?
 Nicotine is a potent parasympathomimetic which
accumulates in the leaves of the Nicotiana tabacum plant.
 Nicotine constitutes approximately 0.6–3.0% of the dry
weight of tobacco and is present in the range of 2–7 µg/kg of
various edible plants. It functions as an antiherbivore being a
potent neurotoxin with particular specificity to insects.
 Nicotine's molecular formula is C10H14N2.

5. History about nicotine
 Nicotine is named after the tobacco plant Nicotiana tabacum, which in
turn is named after Jean Nicot, French ambassador in Portugal, who
sent tobacco and seeds from Brazil to Paris in 1560 and promoted
their medicinal use.
 Nicotine was first isolated from the tobacco plant in 1828 by German
chemists Posselt & Reimann.
 Its chemical empirical formula was described by Melsens in 1843,
and it was first synthesized by A. Pictet and Crepieux in 1893.

6. French scientist that
first found nicotine
Nicolas Louis Vauquelin
was an inventor and
scientist from France. He
discovered nicotine in
1828

7. Chemistry in the nicotine
 Nicotine is a hygroscopic, oily liquid that is miscible with
water in its base form. It forms salts with acids that are
usually solid and water soluble.
 Nicotine easily penetrates the skin.
 Free base nicotine will burn at a temperature below its
boiling point, and its vapors will combust at 95 °F in air.
 Most of the nicotine is burned when a cigarette is smoked;
however, enough is inhaled to provide the desired effects.

8. Structure of nicotine

9. What are receptors of nicotine ?
 The nicotinic cholinergic receptor consists of five subunits.
The brain expresses nine α subunits (α2 through α10) and three β
subunits (β2 through β4). The most abundant receptors are α4β2, α3β4,
and α7, the latter of which are homomeric.
 The α4β2 is the principal mediator of nicotine dependence.
In mice, disruption of the β2 subunit gene eliminates the behavioural
effects of nicotine; reinserting the gene into the ventral tegmental area
restores behavioural responses to nicotine.

10. What are receptors of nicotine ?
 The α4 subunit is an important determinant of
sensitivity to nicotine.
 A mutation affecting a single nucleotide in the
receptor gene increases the hypersensitivity to the
effects of nicotine.
The presence of α5 subunit combined with α4β2
increases calcium conductance seven times; α5 gene
variants also alter nicotine responsiveness in
cultured human cells.

11. NICOTINIC RECEPTORS
 These receptors are found in the central nervous system
(CNS), peripheral nervous systems (PNS) and skeletal
muscles. They are ligand-gated ion channels with binding
sites for acetylcholine and other molecules.
 The nicotinic receptors are made up by different subunits
which determine the quaternary structure of the receptor,
those subunits are α subunits (α1−α10), β subunits (β1−β4),
one δ subunits, one γ subunit and one ε subunit.

12. LOCATION of receptors of nicotine

13. Pharmacology OF nicotine
 As nicotine enters the body, it is distributed quickly through
the bloodstream and can cross the blood-brain barrier.
 On average, it takes about seven seconds for the substance
to reach the brain when inhaled.
 The half life of nicotine in the body is around two hours.
 Nicotine is metabolized in the liver by cytochrome P450
enzymes. A major metabolite is cotinine.

14. PharmacologICAL effectS OF nicotine
 Mainly mediated through release of catecholamines
(adrenaline and noradrenaline).
 Increase in systolic and diastolic blood pressure, heart rate,
force of myocardial contraction, myocardial oxygen
consumption, coronary artery blood flow, myocardial
excitability and peripheral vasoconstriction.
 It also increases serum concentrations of glucose, cortisol,
free fatty acids, antidiuretic hormone and increases platelet
aggregation

15. What are actionS of nicotine?
 When nicotine binds to the receptors it stabilizes the
open state of the ion channel allowing influx of
cations such as potassium, calcium and sodium
ions.
 This binding stimulates the receptors to produce the
clinical effects of nicotine.

16. Nicotine agonists
 A nicotinic agonist is a drug that mimics the
action of Acetylcholine (ACh) at nicotinic
acetylcholine receptors, named for the affinity
for nicotine.
 Examples of nicotinic agonists are nicotine,
acetylcholine choline, epibatidine, lobeline,
varenicline and cytisine.

17. Nicotine antagonists
 A nicotinic antagonist is a type of anticholinergic drug that
inhibits the action of acetylcholine at nicotinic acetylcholine
receptors. These compounds are mainly used for peripheral
muscle paralysis in surgery. For example tubocurarine.
 Some centrally acting compounds such as bupropion,
mecamylamine and 18 methoxycoronaridine block nicotinic
acetylcholine receptors in the brain.

18. MECHANISM OF ACTION OF NICOTINE agonists
and antagonists

19. MECHANISMS, RECEPTORS AND USES OF
NICOTINE antagonists

20. What ARE the effectS OF nicotine?
 Nicotine promotes cancer growth by stimulating angiogenesis and
neovascularisaton.
 Nicotine increases cholinergic signaling (and adrenergic signaling in the
case of colon cancer), thereby impeding apoptosis (programmed cell
death), promoting tumor growth, and activating growth factors and
cellular mitogenic factors .
 Nicotine increases blood pressure and heart rate. Nicotine can also
induce potentially atherogenic genes in human coronary artery
endothelial cells. Microvascular injury can result through its action on
nicotinic acetylcholine receptors.

21. What ARE the effectS OF nicotine?
 Nicotine increases blood pressure and heart rate. Nicotine can also
induce potentially atherogenic genes in human coronary artery
endothelial cells. Microvascular injury can result through its action
on nicotinic acetylcholine receptors.
 Nicotine appears to have significant performance enhancing
effects, particularly in fine motor skills, attention, and memory.
 Studies suggest a correlation between smoking and schizophrenia
, with estimates near 75% for the proportion of schizophrenic
patients who smoke.

22. SIDE EFFECTS OF NICOTINE

23. What ARE the effectS OF nicotine?
 Nicotine also has been shown to have significant deleterious
effects on brain development, including alterations in brain
metabolism and neurotransmitter systems and abnormal
brain development.
 By causing a release of glucose from the liver and adrenaline
from the adrenal medulla, it causes stimulation.

24. What ARE the effectS OF nicotine?
 Nicotine appears to enhance concentration and memory due
to the increase of acetylcholine. It also appears to
enhance alertness due to the increases of acetylcholine and
norepinephrine.
 Nicotine also extends the duration of positive effects of
dopamine and increases sensitivity in brain reward systems.
 Pain is reduced by the increases of acetylcholine and beta-
endorphin.

25. LOCATION OF SITES OF NICOTINIC
RECEPTORS

26. NICOTINE ADDICTION
The criteria to diagnose nicotine addiction include any 3 of the following
within a 1-year time span:
 Tolerance to nicotine with decreased effect and increasing dose to obtain
same effect
 Withdrawal symptoms after cessation
 Smoking more than usual
 Persistent desire to smoke despite efforts to decrease intake
 Extensive time spent smoking
 Postponing work, social, or recreational events in order to smoke
 Continuing to smoke despite health hazards

27. Treating nicotine addiction
 Mode of Action : Substitute source of nicotine to
achieve and sustain tobacco abstinence
 Using :
Nicorette chewing gum
Nicorette inhaler
Niquitin patch
Niquitin lozenges

28. NICOTINE ADDICTION AND ABUSE
 Most smokers use tobacco regularly because they are
addicted to nicotine. Addiction is characterized by
compulsive drug seeking and abuse, even in the face of
negative health consequences.
 Most smokers identify tobacco use as harmful and express a
desire to reduce or stop using it, and nearly 35 million of
them want to quit each year. Unfortunately, more than 85
percent of those who try to quit on their own relapse, most
within a week.

29. NICOTINE ADDICTION AND ABUSE
 Of primary importance to its addictive nature are
findings that nicotine activates reward pathways—
the brain circuitry that regulates feelings of pleasure.
 A key brain chemical involved in mediating the
desire to consume drugs is the neurotransmitter
dopamine, and research has shown that nicotine
increases levels of dopamine in the reward circuit.

30. ADVERSE REACTIONS OF NICOTINE
DEPENDENCE TREATMENT
 Nausea, vomiting, dyspepsia, upper abdominal pain,
diarrhea, dry mouth, constipation, hiccups, stomatitis,
flatulence, oral discomfort, headache, dizziness,
tremor, sleep disturbances
 e.g. insomnia and abnormal dreams, nervousness,
palpitations, pharyngitis, cough, pharyngolaryngeal
pain, dyspnea, increased sweating, arthralgia, myalgia,
chest pain ,pain in the limb, asthenia, fatigue

31. NICOTINE WITHDRAWAL
 Nicotine withdrawal is classified as a nicotine-induced
disorder.
 Symptoms include difficulty concentrating, nervousness,
headaches, weight gain due to increased appetite,
decreased heart rate, insomnia, irritability, and depression.
These symptoms peak in the first few days but eventually
disappear within a month. For some people, however,
symptoms may persist for months.

32. NICOTINE WITHDRAWAL
 Many behavioral factors can also affect the severity of
withdrawal symptoms.
 For some people, the feel, smell, and sight of a cigarette and
the ritual of obtaining, handling, lighting, and smoking the
cigarette are all associated with the pleasurable effects of
smoking and can make withdrawal or craving worse.

33. TREATING NICOTINE WTHDRAWAL
 Nicotine replacement therapies such as gum, patches, and
inhalers may help alleviate the pharmacological aspects of
withdrawal; however, cravings often persist.
 Behavioral therapies can help smokers identify
environmental triggers of craving so they can employ
strategies to prevent or circumvent these symptoms and
urges.

34. CONCLUSION
 Nicotine is a potent parasympathomimetic present in
cigarettes and tobacco.
 Nicotine binds to and stimulates nicotinic receptors of
acetylcholine causing nicotinic effects. These effects are
addictive and detrimental to the body.
 Withdrawal from nicotine use causes withdrawal symptoms
that can be treated with nicotine replacement therapy or
behavioral therapy.

35. references
 Benowitz N.L., 1986 Clinical Pharmacology of Nicotine Annual Review of
Medicine 37 (1): 21
 Lande R.G. , Dunayevich E 2014 Nicotine Addiction Clinical Presentation
Medscape emedicine.medscape.com
 Levin E.D., McClernon F.J., Rezvani A.H., 2006 Nicotinic effects on
cognitive function: behavioral characterization, pharmacological
specification, and anatomic localization Psychopharmacology Vol 184
Issue 3-4: pg 523 -539
 Petersdorf, Adams, Braunwald, Isselbacher, Martin, Wilson Harrison’s
Principles of Internal Medicine 10 th Edition pg 1032-1303

36. references
 http://www.medicalnewstoday.com/articles/240820.php
 http://www.researchgate.net/post/Nicotinic_Receptors_Nicoti
ne_addiction

37. Thank you