Alkaloids are nitrogen-containing plant compounds that are physiologically active. They include morphine and atropine. Morphine is a pain reliever isolated from opium poppies. It acts on mu-opioid receptors in the brain and spinal cord to reduce pain. Atropine is a tropane alkaloid with anticholinergic effects. It blocks muscarinic acetylcholine receptors and is used as an antidote for nerve agent poisoning and as a treatment for bradycardia.

1. the term “alkaloid” (alkali-like) is
commonly used to designate basic
heterocyclic nitrogenous compounds
of plant origin that are physiologically
active.

2. Deviation from Definition:
 Basicity: Some alkaloids are not basic e.g.
Colchicine, Piperine, Quaternary alkaloids.
 Nitrogen: The nitrogen in some alkaloids is not in
a heterocyclic ring e.g. Ephedrine, Colchicine,
Mescaline.
 Plant Origin: Some alkaloids are derived from
Bacteria, Fungi, Insects, Animals

3. New Definition:
Alkaloids are cyclic organic compounds
containing nitrogen in a negative state of
oxidation with limited distribution among
living organisms.

4. Nomenclature:
Trivial names should end by "ine". These names may refer to:
From plant generic name (Atropine)
From specific plant species (Cocaine)
From the common name of Drug (Ergotamine)
From physiological activity (emetine)
From the name of discoverer (Pelletierine)
From the prominent Physical character (Hygrine)

5. Distribution in Plant:
All Parts e.g. Datura.
Barks e.g. Cinchona
Seeds e.g. Nux vomica
Fruits e.g. Black pepper
Latex e.g. Opium
Leaves e.g. Tobacco

6. According to basicity Alkaloids are classified
into:
Weak bases e.g. Caffeine
Strong bases e.g. Atropine
Neutral alkaloids e.g. Colchicine

7. Extraction of
alkloids:
Crude drug
powdered
Dil.acid/H2O
Filter
Filtrate basify
+
chloroform
Marc
Organic layer acidify
+
acid
Aq.layer
(sugar,
carbohydrate)
Org. layer basify+ chloroform Aq. Layer
fats., wax etc
Organic layer
Aq.layer
Alkaloids

8. CLASSIFICATION OF
ALKOLOIDS

10. TRUE ALKOLOIDS
True alkoloids derived from amino acids
Heterocyclic ring with nitrogen
Highly reactive substances in low doses also
Bitter taste with white appeareance
Form water soluble salts
examples: cocaine, morphine, nicotine,
dopamine etc.

11. Classification of Alkaloids
 Chemical Classification:
 1) Phenyl Ethyl Amine Alkaloids:
 drugs: ephedrine, adrenaline, noradrenaline
O H
N H
e p h e d r i n e
H
2
N
p
h
e
n
y
l
e
t
h
y
l
a
m
i
n
e

12. 2) Pyrrolidine alkaloid:
e.g hygrine, cuscohygrine
N H
p y r r o l i d i n e
3)Pyridine and piperidine alkaloids:
e.g pyridine and piperidne
N
p y r i d i n e
N H
p i p e r i d i n e

13. 4)Pyrolidine-pyridine alkaloids: also called tobacco alkaloids.
e.g nicotine, atrpoine, cocaine
N
N
nicotine
5) Quinone alkaloids:
e.g cinchonine and quinine
OH
N
H
O
N
quinine
O O
q
u
i
n
o
n
e

14. 6) Iso-quinoline alkaloids:
examples: papaverine
N
iso-quinoline
7) Phenanthrene alkaloids:
e.g Morphine, codeine and thebaine
H
O
O
H
O
H
N
m
o
r
p
h
i
n
e
p
h
e
n
a
n
th
r
e
n
e

15. 8) Indole alkaloids:
e.g gramine
N
H
in d o le
gramine

16. MORPHINE

17. MORPHINE
 Morphine is the most abundant opiate found
in opium, the dried latex extracted by shallowly
scoring the unripe seedpods of the Papaver
somniferum poppy. Morphine was the first active
principle purified from a plant source and is one
of at least 50 alkaloids of several different types
present in opium.
 Morphine is an opioid analgesic drug. Morphine
has a high potential
for addiction; tolerance and psychological depen
dence develop rapidly,
although physiologicaldependence may take
several months to develop.
H
O
O
H
O
H
N
m
o
r
p
h
i
n
e

18. Morphine was first isolated in 1804 by Friedrich
Sertürner, which is generally believed to be the
first ever isolation of a natural plant alkaloid in
history.
Sertürner originally named the
substance morphium after the Greek god of
dreams, Morpheus (Greek: Μορφεύς), for its
tendency to cause sleep

19. CHEMISTRY
 Morphine is a phenanthrene alkaloid with two additional ring
closures. It has:
 A rigid pentacyclic structure consisting of a benzene ring
(A), two partially unsaturatedcyclohexane rings (B and C),
a piperidine ring (D) and a tetrahydrofuran ring (E). Rings A,
B and C are the phenanthrene ring system. This ring system
has little conformational flexibility.

20. Structure activity relationship

26. USES
Relief of pain caused by heart attack or
myocardial infarction.
Relief of the severe bone and joint pain
associated with sickle cell crisis.
Pain relief before, during and after surgery.
General anesthsia to sedate a patient.
A cough suppressant in cases where cough is
severe enough.

27. MECHANISM OF ACTION
 Opioid receptors
 As morphine binds to opioid receptors, molecular signalling activates the
receptors to mediate certain actions.
 There are three important classes of opioid receptors and these are:
 μ receptor or Mu receptors - There are three subtypes of this receptor, the μ1, μ2
and μ3 receptors. Present in the brainstem and the thalamus, activation of these
receptors can result in pain relief, sedation and euphoria as well as respiratory
depression, constipation and physical dependence.
 κ receptor or kappa receptor - This receptor is present in the limbic system, part
of the forebrain called the diencephalon, the brain stem and spinal cord.
Activation of this receptor causes pain relief, sedation, loss of breath and
dependence.
 δ receptor or delta - This receptor is widely distributed in the brain and also
present in the spinal cord and digestive tract. Stimulation of this receptor leads
to analgesic as well as antidepressant effects but may also cause respiratory
depression.

28. Synthesis of Morphine
O H
C H 2 C O O H
O C H 3
4 , m e t h o x y - 3 , h y d r o x y p h e n y la c e t ic a c id
+
H 3 C O
N H 2
3 - m e t h o x y p h e n y le t h o la m in e
O N H
H 3 C O
H O
H 3 C O
N
C H 2
H 3 C O
H O
H 3 C O
- H 2 O
P O C l3
3-methoxyphenylethaneamine
X

29. CH2
NH
H3CO
HO
O CH3
CH3I
HO
O CH3
CH2
N
H3CO
CH3
Birch Reduction
Na/NH3
ethanol
HO
O CH3
CH2
N
O
CH3
HCl
N CH3
O
H3CO
HO
Na/Hg.
Ethanol

30. N C H 3
O
H 3 C O
H O
B r
B r
B r 2 -H B r
N C H 3
O
H 3 C O
B r
O
H
B e ta -e lim in a tio n
r e a c tio n
- H B r
N C H 3
O
H 3 C O
O
LiAlH4
O
O
HO H
N
CODEINE
H
I
H O
O
H O H
N
M O R P H I N E
CH3I
Thebaine

31. Atropine:
O H
O N
O
a t r o p i n e
T r o p i n e g r o u p
b i c y c l i c r i n g
e s t e r g r o u p
t r o p i c a c i d

32. Chemistry:
 Atropine belongs to pyrolidine-pyridine group of alkaloids.
 It contains tropine skeleton and tropic acid in their structure and that is why it is also
called bridge compound.
OH
O
OH
tropic acid

33. Description:
 Occurs as colorless needle like crystals or white powder.
 Optically inactive
 Bitter in taste
 Its saturated solution is alkaline in nature
 not soluble in water but soluble in alcohol

35. OH
O N
O
atropine
N
X: ester
R2
R1:CH2OH
R3:H
SAR:

36. SAR:
 For maximal activity, R1 and R2 positions should be either carboxylic or
heterocylic rings or one may be carbocylic .
Note: carboxylic means all rings have carbon while heterocyclic means one ring
should be non-carbon.
 Among these rings one ring should be aromtic and one is saturated or both
should be saturated for maximal activity.
 For maximal activity,R3 should be hydrogen , OH or hydroxymethyl group.
 For maximal activity , X position should be ester group while in some cases
ester can be replaced by oxygen atom also.

37. SAR:
 Quaternary amine have maximal activity than tertiary amine in case of
basic nitrogen atom.
 Most potent antimuscarinic agents must have two methylene groups for
maximum activity.
 If R2 group is replaced by OH group, duration of action becomes short.

38. Uses:
• Anesthetic
• Vasoconstrictor.
• CNS stimulant
• Dental anaesthetic
• Local anaesthetic