ALKALOIDS

OBJECTIVES
To know what are the characteristics of
alkaloids
To know the different sources of alkaloids
To determine the importance of alkaloids and
to identify their applications in pharmacy
To know the different test in determining the
presence of alkaloids
 WHAT ARE ALKALOIDS?

These are commonly applied to basic

nitrogenous compounds of plant origin
that are physiologically active.
Organic nitrogenous compounds with a
limited distribution in native nature.
STRUCTURE OF ALKALOIDS
 CHARACTERISTICS:
They are bitter in taste.
Derived from amino acids
Alkaloids form double salts with
compounds of mercury, gold, platinum
and other heavy metals. These salts are
obtained as precipitate which are
microcrystallographic.
 Most but not all alkaloids possess
basic properties owing to the
presence of amino nitrogen.
Structurally complex end products of
energy- requiring reaction
sequences.
 Alkaloids usually contain one nitrogen
atom but some may contain 5 nitrogen
atoms such as ergotamine. The
nitrogen may exist as a primary amine
(RNH2), secondary amine (R2NH),
tertiary amine (RN), or as quaternary.
PROPERTIES OF ALKALOIDS

Insoluble or sparingly soluble in water,

but the salts formed on reaction with
acids are usually freely soluble.
Most are crystalline solids although a
few are amorphous.
 Free alkaloids are usually soluble in
ether, chloroform, or other relatively
non-polar immiscible solvents.
Some alkaloids are liquid because of
lacking of oxygen in their molecules.
(e.g coniine, nicotine, spartenine)
 The degree of basicity varies greatly,
depending on the structure of the
molecule and the presence and
location of other functional groups.
Have high melting points
 SOURCES AND OCCURRENCE OF ALKALOIDS

Alkaloids can occur in plant kingdoms;

among the angiosperms, the
Leguminosae, Papaveraceae, Ranunculaceae,
Rubiaceae, Solanaceae, and Berberidaceae

are outstanding alkaloid-yielding

plants.
 The Labiatae and Rosaceae are almost
free of alkaloids; the gymnosperms only
rarely contain them (Taxaceae).
Specific alkaloids are confined to specific
plant families such as hyoscyamine in
Solanaceae, colchicine in Liliaceae
 Although it has been claimed that the
monocotyledons do not generally
produce alkaloids, investigations indicate
that the Amaryllidaceae and Liliaceae are
two of the most promising families (of a
list 11) in which to search for alkaloid-
yielding plants.
 Occur in fungi (e.g ergot from Claviceps
purpurea)
Occur in various parts of the plant; in
seeds (physostigma, areca),
underground stems (sanguinaria), roots
(belladonna root), rhizomes and roots
(ipecac, hydrastis), barks (cinchona).
USES OF ALKALOIDS IN PLANTS:

Poisonous agents which protect plants

against insects and herbivores
End products of detoxification reactions
representing a metabolic locking-up of
compounds otherwise harmful to the
plants.
 For regulatory growth factors
Reserve substance capable of
supplying nitrogen or other elements
necessary to the plants economy
PHARMACOLOGIC ACTION OF ALKALOIDS:

Analgesic (morphine, codeine)

Narcotics (strychnine, brucine which
are central stimulant)
Mydriatics (atropine)
Miotics (physostigmine, pilocarpine)
Ephedrine (rises in blood pressure)
Reserpine (produce fall in excessive
hypertension)
BIOSYNTHESIS OF ALKALOIDS
 The biosynthesis of many alkaloidal
structures can be rationalized through
simple chemical reactions that involve
amino acids.
The amino acids that are most often
serve as alkaloidal precursors are:
phenylalanine, tyrosine, tryptophan, histidine,
anthranilic acid, lysine and ornithine.
 Some of the general reactions that are of
particular importance include: decarboxylation

(removal of carboxyl group or carbon dioxide)

and transamination (transfer of an amino group
from one molecule to another without the
formation of ammonia) of the amino acids to
yield a corresponding amine or aldehyde.
These can react to form a Schiff base which, in
turn can react with carbanion in a Mannich-
type condensation.
TEST FOR ALKALOIDS
Wagners Test
(+) Reddish brown precipitate
Reagent used: Wagners Reagent
[Solution of iodine in potassium iodide]

Mayers Test
(+) Cream color precipitates
Reagent used: Mayers Reagent
[Potassium mercuric iodide solution]
Dragendorffs test
(+) Orange precipitate

Reagent used: Dragendorffs reagent

[Potassium bismuth iodide solution]
Hager's test

(+) Yellow color precipitate

Reagent used: Hager's reagent

[saturated solution of Picric acid]
Tannic acid test

(+)buff color precipitate

Reagent used: 10% Tannic acid solution

Valsers Test

(+) white precipitate

Reagent used: Valsers reagent

(Mercuric Iodide TS
NAMING FOR ALKALOIDS

From the generic name or the genus of the plant

yielding them (e.g hydrastine, atropine)
The specific name or species of the plant yielding
alkaloids ( e.g cocaine, belladonnine)
Common name of the drug yielding them (e.g
ergotamine)
 From their physiologic activity (e.g
emetine, morphine)
From the discoverer (e.g pelletierine)

~ All names of alkaloids should end in -ine.

~ A prefix or suffix is added to the name of a

principal alkaloid from the same source.
(quinine, quinidine, hydroquinine)
CLASSIFICATION OF ALKALOIDS

Pyridine- Piperidine Combined

Tropane
Quinoline
Isoquinoline
Indole
Imidazole
Steroid
Alkaloidal amine
Purine
PYRIDINE- PIPERIDINE COMBINED

Also referred to as Pyrrolizidine

alkaloids

Upon reduction, the tertiary base,

pyridine, is converted into the
secondary base, piperidine.
3 Subgroups
Derivatives of piperidine
Derivatives of nicotinic acid
Derivatives of both pyridine and
pyrrolidine
Important alkaloidal drugs and alkaloids
that are classified in this group are:

Areca
Arecoline
Hydrobromide
Lobelia
Lobeline
Nicotine
NICOTINE

A primarily product of
root metabolism, but
the formation of small
amounts, as well as
subsequent reactions
such as demethylation
of nicotine, can occur
in leaves of plants.
 It is a pyridine alkaloid obtained from
the dried leaves of the tobacco plant
Nicotiana tabacum Linn (Fam.
Solanaceae)
Nicotiana was named after Jean

Nicot who introduced tobacco in

Europe
 Tabacum refers to the Indian name
for the pipe or tube used in smoking it
It is colorless to pale yellow, very
hygroscopic, oily, volatile liquid with
unpleasant, pungent odor and a sharp,
burning, persistent taste.
USES:
It is bound to an ion exchange resin in a
chewing gum base as a temporary aid to
the cigarette smoker seeking to give up
smoking.
Chronic use of nicotine may result in
psychological and physical dependence.
ARECA

Areca nut or Betel

Nut
A dried, ripe seed of
Areca catechu
(Fam. Palmae)
Areca- a Spanish
and Portuguese
term for betel nut
 Catechu- East Indian name for an
astringent extract or juice
Areca mixed with lime, the leaves of Piper
bette Linn and occasionally gambir is
known as PUNSUPARI. This mixture is
used as a stimulant masticatory.
Consists of 0.45% alkaloids, 15% tannins,
lipids, volatile oils and gum.
Uses:
Pharmaceutic purposes
Anthelmintic or vermicide in veterinary
practice
Taenifuge
Constituents: These are reduced
pyridine derivatives.
Arecoline (arecaidine methyl ester) <most
abundant and physiologically active>
Arecaidine (N-methyl guvacine)
Guvacine (Tetrahydronicotinic acid)
Guvacoline (Guvacine methyl ester)
LOBELIA

Indian tobacco
Consists of dried leaves
and tops of Lobelia
inflata Linn (Fam.
Lobeliaceae)
Lobelia named in
honour of a Flemish
botanist Matthias de L
Obel
 Inflata refers to a hollow and distended
fruit
Substitute for tobacco

Uses:
Similar but weaker pharmacological effects
in nicotine on the peripheral circulation,
neuromuscular junctions, and CNS.
Anti-smoking preparations
 Lobeline sulfate incorporated in tablets or
lozenges are smoking deterrents.
Lobeline had placebo effect on decreasing the
physical craving for cigarettes.
Traditionally used by the Native Americans for
asthma
Chronic bronchitis

Injection of lobeline hydrochloride is used in

the resuscitation of newborn infants

Constituents:
Contains 14 alkaloids which
LOBELINE is the major and most important.
It has a pungent, volatile oil, resin, lipids,
and gum.
Lobeline, (-) lobeline or alpha lobeline
This occurs as colorless crystals which are
slightly soluble in water but readily soluble in
hot alcohol.
TROPANE ALKALOIDS

A dicyclic compound formed by the condensation

of a pyrrolidine precursor (ornithine) with three
acetate-derived carbon atoms. Both pyrrolidine
and piperidine ring system can be discerned in
the molecule.
The 3-hydroxy derivative of tropane is known as
tropine. Its esterification with (-)- tropic acid
yields hyoscamine (tropine, tropate), which may
be racemized to form atropine.
Important alkaloidal drugs and alkaloids
that are classified in this group are:

Belladonna leaf
Hyoscyamus
Stramonium
Atropine
Hyoscyamine
Scopolamine
Coca
Cocaine
BELLADONNA

Belladonna leaf,
Belladonna herb or deadly
nightshade leaf

Consists of dried leaf and

flowering or fruiting top of
Atropa belladonna Linn or
of its variety acuminata
Royle ex Lindley (Fam.
Solanaceae)
 Atropa is from Atropos meaning
inflexible
Belladonna from Italian word
bella meaning beautiful and donna
meaning lady

Uses:
It acts as an antimuscarinic agent
which accounts for its use as a
 Used as a adjunctive therapy in the treatment
of peptic ulcer; functional digestive disorders
It possesses anticholinergic properties and is
used to control excess motor activity of the GI
tract and spasm of the urinary tract.
It is commonly administered in the tincture
(3mg alkaloids/ 100ml) or the extract (1.25 g
alkaloids/100g)
Constituents:

(-)- hyoscyamine
remainder atropine
Apoatropine
Belladonnine
Cuscohygrine
Scopolamine
 SOLANACEOUS ALKALOIDS

The principal alkaloids of this group are:

(-) hyoscyamine
atropine [() hyoscyamine]
scopolamine (also known as hyoscine)
These are tropine derivatives and esters and may
be prepared synthetically but are usually
obtained by extraction from plants of the
Solanaceae such as:
Atropa belladonna
Datura stramonium
Hyoscyamus niger
Hyoscyamus muticus (also known as Henbane)
Dubosia plants
Atropine
An antidote in case of poisoning
caused by cholinesterase inhibitors.
It is a CNS stimulant.
Scopolamine
It has a depressant activity on the CNS.
It is used to treat motion sickness.
It is employed for preanesthetic
sedation and for obstetric amnesia in
conjunction with analgesics and to
calm delirium.
Toxicity symptoms occur in using
atropine, scopolamine and belladonna
tincture include:
Skin rash

Skin flushing

Mouth dryness

Difficulty in urination

Eye pain

Blurred vision

Light sensitivity
Hyoscyamine
a tropine ester of (-)-tropic acid

Hyoscyamine sulfate
extremely poisonous
It occurs as white, odourless crystals or as
crystalline powder.
It is a deliquescent and is affected of light.
 It is an anticholinergic and used as an
aid in the control of gastric secretion,
visual spasm, hypermotility in spastic
colitis, pylorospasm and abdominal
cramps.
In Parkinsonism, it is used to reduce
rigidity and tremors and to control
associated sialorrhea and
Atropine sulfate
It occurs as colorless crystals or as a
white, crystalline powder.
It is extremely poisonous.
It effloresces in dry air and is slowly
affected by light.
It is an anticholinergic, used in surgery as
an antisialogogue.
Scopolamine or hyoscine
An alkaloid abundant in Datura fastuosa var.
alba and in D. Metel.
It is an ester that, upon hydrolysis, yields
tropic acid and scopoline.
It occurs as an almost colorless, syrupy
liquid from its chloroformic solution and
colorless crystals from its ether solution.
LEVOROTATORY
Scopolamine hydrobromide or hyoscine
hydrobromide
It occurs as colorless or white crystals or as a white,
granular powder that is odourless and slightly
efflorescent in dry air. It is extremely poisonous.
It is classified as anticholinergic.
It is employed for preanesthetic sedation and for
obstetric amnesia in conjunction with analgesics
and to calm delirium. It is administered SC or IM in a
single dose.
Hyoscyamus
Also known as Henbane
dried leaf with or without the stem
and flowering or fruiting crop of
Hyoscyamus niger Linn (Fam.
Solanaceae)
It contains not less than 0.04%
alkaloids of hyoscyamus.
 Hyoscyamus (a Greek and Latin
name formed from two Greek words,
meaning hog and bean.
The plant is poisonous to swine.
The alkaloids, hyoscyamine and
scopolamine, 0.05% to 0.15% of
which three fourths is hyoscyamine
are the active ingredients.
HYOSCYAMUS
STRAMONIUM

Also known as Jimson

weed, Jamestown
weed
dried leaf with or
without the stem and
flowering or fruiting
crop of Datura
stramonium Linn
(Fam. Solanaceae)
 It yields not less than 0.25% of alkaloids.
Datura (from Sanskrit dhatura, and from
Arabic tatura or tatula, the native name)
Stramonium (from the French word
stramoine meaning stinkweed)
It was used as a pot herb
It can serves as atropine
STRAMONIUM SEED

from D. stramonium
The seed contains
0.4% of alkaloids,
principally
hyoscyamine with a
small portion of
scopolamine and
traces of atropine.
 It is generally regarded as a noxious weed
and has frequently caused poisoning in
children when seeds were ingested.
The chief toxic symptoms are those of
atropine:
Dilated pupils

Impaired visions

Dryness of the skin

Secretions

Extreme thirst

Hallucination

Loss of consciousness
COCAINE
Coca leaves or Coca
Dried leaves of
Erythroxylum coca
Lamarck which is
commercially known as
Huanuco coca or of E.
truxillense Rusby
Truxillo coca (Fam.
Erythroxylaceae)
 Erythroxylum (is from the two Greek
words meaning red and wood)
Coca ( is the Spanish name for the tree)
Truxillense (from Truxillo a coastal city
in Peru)
Contains three basic types of alkaloids:
Derivatives of ecgonine

Derivatives of tropine

Derivatives of hygrine
Huanuco coca
Contains 0.5 to 1% of ester
alkaloids, derivatives of tropine and
ecgonine
Cuscohygrine is the principal
nonester alkaloid in the leaf.
Truxillo coca
Has lower content of ester alkaloids
but higher percentage of cocaine
(75%)
The shrub was known as The Divine
Plant of the Incas
 Cocaine hydrochloride
Colorless crystals or as a white,
crystalline powder.
Ingredient in Bromptons cocktail
Use to control severe pain
CNS stimulant
Administered IV or SC while cocaine free-
based is smoked
Crack
extremely addictive smokable forms
of cocaine processed from cocaine
hydrochloride
Its name refers to the sound made
when rocks of cocaine are smoked.
QUINOLINE ALKALOIDS

These are alkaloids which contain quinoline as their

nucleus including those obtained from cinchona
(quinine, quinidine, cinchonine, and cinchonidine)
Cinchona and its alkaloids are the only members of
this group that are therapeutically important at
present. Cinchonine, is isomeric with cinchonidine
which is the parent alkaloid of the quinine series.
Quinine and its isomer, quinidine, represent 6-
methoxycinchonine.
CINCHONA BARK
 Cinchona bark or Peruvian bark
dried bark of the stem or of the root of
Cinchona succirubra Pavon et Klotzch or its
hybrids, known in commerce as red cinchona
or of C. ledgeriana (Howard) Moens et
Trimen, C. calisaya Weddell, or hybrids of
these with other species of Cinchona, known
in commerce as calisaya bark or yellow
cinchona (Fam. Rubiaceae)
 Cinchona (named in honor of the
Countess of Chinchon, wife of viceroy of
Peru)
Succirubra (Latin word meaning red
juice)
Calisaya (a tree)
Ledgeriana ( named in honor of
Charles Ledger)
 Cinchona toxicity results in temporary loss
of hearing and in impaired sight. Ringing in
the ears is one of the symptoms of toxicity.
When these symptoms are produced as the
result of continuous use of cinchona or of
quinine. The condition has been called
cinchoism.
Cinchona was formerly given in doses of 1g.
CUPREA BARK
obtained from Remijia purdieana Triana and
R. Pedunculata Fluckiger (Fam.Rubiaceae)
it has a copper red color hard , compact, and
heavy it contains numerous transversely
elongated stone cells and 2-6 % of alkaloids of
which 1/3 maybe quinine its a commercial
source of quinidine.
CINCHONA ALKALOIDS

Quinidine
Its a stereoisomer of quinine and is
present in cinchona barks to the extent
of 0.25-1.25%.
It depresses myocardial excitability,
conduction velocity and to a lesser
extent, contractility.
 Use to treat various cardiac
arrhythmias such as mature atrial , AV
junctional, and ventricular contractions
: atrial flutter and atrial fibrilations.
When administered orally, the peak
serum levels are slightly lower with the
gluconate and poylgalacturonate salt
than with sulfate salt .
 The usual real dose available is 10 to 20
mg/kg/day in 4 to 6 divided doses in order to
obtain the average therapeutic serum levels
of 3 to 6mcg/ml.
A toxic reaction occurs at levels above
8mcg/ml.
The patient should be instructed to notify the
physician if skin rash,fever,unusual
bleeding/bruising,ringing in the ears,or visual
disturbance occurs.
Quinidine sulfate
sulfate of an alkaloid obtain from cinchona from
Remijia pedunculata or prepared from quinine.
It occurs as fine needle like white crystals that
frequently cohere in masses.
It is odorless , has a bitter taste and darkens
when exposed to light.
It is readily soluble in water, alcohol, methanol
and chloroform.
Quinidine gluconate
It occurs as a white powder odorless
and has a bitter taste available in
sustained release tablet.
Quinidine polygalacturonate
It affords control and more uniforms
absorptions through the intestinal
mucosa than does quinidine sulfate.
In addition it produces a lower
incidence of GI irritation
Quinine
Diastereoisomer of quinidine
It occurs as white, odourless, bulky
crystals or as a crystalline powder.
It darkens when exposed to light and
effloresces in dry air.
It is freely soluble in alcohol, ether and
chloroform but slightly soluble in water.
Quinine Sulfate
a sulfate of an alkaloid obtained from the
bark of Cinchona species.
A white, odourless, bitter, fine, needlelike
crystals that are usually lusterless.
It becomes brownish when exposed to light.
It is not readily soluble in water, alcohol,
chloroform or ether.
Uses
Antimalarial
For treating of chloroquinine resistant falciparum
malaria combination with pyrimethamine and
sulfadoxine or tetracycline or clindamycin.
It has a skeletal muscle relaxant effect.
It is widely used for the prevention and
treatment of nocturnal recumbency leg cramps.