ALKALOIDS

Alkaloid Definition
Alkaloid: Difficult to define
No definitive difference between
an alkaloid and naturally
occurring complex amines.

Alkaloids: plant derived, are alkali
and contain at least one N2-
atom. They also normally
have a significant physiological
action on humans and
animals.
Proto-alkaloid/ amino-alkaloid
applied to compounds which
lack one or more of the
properties of typical alkaloids.

Other alkaloids which do not
conform with the general
definition are synthetic
compounds not found in plants
but are very closely related to
natural alkaloids.
Alkaloid Description
Contains nitrogen - usually derived from an amino
acid.
Bitter tasting, generally white solids (exception -
nicotine is a brown liquid).
They give a precipitate with heavy metal iodides.
Caffeine, a purine derivative, does not precipitate like
most alkaloids.
Alkaloids are basic - they form water soluble
salts. Most alkaloids are well-defined crystalline
substances which unite with acids to form salts.
In plants, they may exist
in the free state,
as salts or
as N-oxides.
Occur in a limited number of plants. Nucleic acid
exists in all plants, whereas, morphine exists in
only one plant species.
Tests for Alkaloids
Most alkaloids are precipitated from neutral or slightly
acidic solution by
Mayer's reagent (potassiomercuric iodide solution)
Cream coloured precipitate.
Dragendorff's reagent (solution of potassium bismuth
iodide) orange coloured precipitate.
Wagners reagent (iodine in potassium iodide) red-
brown precipitate
Hagers reagent (picric acid) yellow precipitate

Caffeine does precipitate
Occurrence, Distribution & Location
of Alkaloids
Occur in bacteria (Pseudomonas
aeruginosa) and rarely in fungi
(pscilocin from hallucinogenic
mushrooms).
Some alkaloids occur in several
genera from different species
(caffeine), but most occur in
closely related species.
Some occur in certain families
(hyoscyamine), while others
occur only in a specific species
(morphine).
Rarely do plants contain more
than 1 type of alkaloid.
All alkaloids of one plant will have
a common biogenenetic origin

Alkaloids occur in all plant
parts, but are usually
localized in one organ (e.g.
the bark or seeds).
Within the plant, [alkaloid] can
vary widely from part to part
some parts may contain no
alkaloids.
Occasionally, different alkaloids
also form in different parts of
the plant.
Alkaloid concentrations occur in
wide ranges e.g.
Madagascan periwinkle
contains 3g per (anti-cancer)
alkaloids per tonne of
leaves.


The Nitrogen of Alkaloids

The N2 atom can either be
1, 2, 3 or 4
(quaternary).

This N2 feature affects the
alkaloid derivatives
which can be prepared
and the isolation
procedures.

Physical-Chemical Properties of
Alkaloids
MW: 100 900
Most bases which do not contain O2 are liquid at
room temperature (nicotine), while those that do
are solids. In rare cases they are coloured.
Most solid bases rotate the plane of polarized light,
have high melting points.
Normally are not soluble in water (occasionally
slightly soluble).
Soluble in apolar or slightly polar organic solvents.
Soluble in concentrated hydroalcoholic solutions
The basicity of alkaloids depends on the availability of the
lone pair of e- on the N2 atoms: e- donating groups
enhance basicity, while e-withdrawing groups decrease
it.
Because some alkaloids have a carbonyl group on the
amide, they can also be neutral (colchicine & piperine).
Basicity is also influenced by steric constraints.

Basic characteristic renders complex alkaloids unstable, so
that in solution they are sensitive to heat, light & oxygen.

Basic character of alkaloids also allows them to form salts
with mineral acids (such as hydrochlorides, nitrates and
sulphates) or inorganic acids (tartrates, sulfamates).

Alkaloid salts are soluble in water and dilute alcohols.
Solid salts can be conserved well and are a common
commercial form of alkaloids.
Classification of Alkaloids
Alkaloids have a large variety in their botanical &
biochemical origin, in chemical structure and
pharmaceutical action. Therefore, like flavonoids, a
range of different classification systems exist for
grouping alkaloids.

They can therefore be classified according to their
Biological origin
Chemical structure - 2 divisions
i. Atypical/non-hetrocyclic alkaloids (protoalkaloids or
biological amines)
ii. Typical/hetrocyclic alkaloids (divided into 14 groups
according to their ring structure)
Biosynthetic pathway

Naming of Alkaloids
Numerous methods can be used
to name alkaloids
Generic plant name atropine
from Atropa belladonna
Specific name of the plant
cocaine from Erythroxylum coca.
Common name of the herb
ergotamine from ergot (rye)
Physiological action of the plant
emetine producing emesis
Other e.g. morphine derived
from ancient Greek mythology
Morpheus god of dreams

Extraction of Alkaloids
Extraction is based on the basicity of
alkaloids and on the fact that they normally
occur in plants as salts (i.e.: on the
solubility of bases and salts in water and
organic solvents).
Herbs often contain other materials which
can interfere with extraction such as large
amounts of fat, waxes, terpenes, pigments
and other lipophilic substances (e.g by
forming emulsions) avoided by defatting
the crushed herb (using petroleum ether
and hexane)
Alkaloid Extraction
Extraction method normally
depends on the raw
material, the purpose of
extraction & the scale on
which is to be performed.

For research purposes:
chromatography allows
for quick and reliable
results.

If larger amounts of
alkaloids need to be
extracted, one of the
following methods can be
used.











TLC plate
Extraction in an Alkaline Medium
Step 1: Powdered, defatted herb is mixed with an alkaline
aqueous solution.

This displaced alkaloids from their salt combinations.

Free bases are then extracted with organic solvents.

Normally aqueous ammonia is used, but a carbonate
solution is used when alkaloids contain fragile elements
such as a ester or lactone.

In some cases, e.g. Cinchona bark, a mixture of calcium
hydroxide & sodium hydroxide should be used as the
alkaloids are bound to tannins.

Organic solvent: chloroform, dichloromethane or ethyl
acetate depends on the toxicity, safety, cost & ease of
recovery and recycling of the solvent).
The Soxhlet Apparatus
Industry: uses solid-liquid
extractors based on the
principle of counter-current
extraction, such Soxhlet
apparatus.












Extraction of Alkaloids: Step II
Organic solvent containing
alkaloids (bases) is separated
from residue & concentrated
by distillation under pressure if
needed.

Solvent is stirred with an acidic
aqueous solution: alkaloids go
into the solution as salts.
Impurities remain in the
organic phase.

Repeated until the organic phase
no longer contains alkaloids.

Many acids can be used (HCL,
Sulfuric, citric, tartaric), but
always in very dilute
concentrations (1-5%)

Alkaloid Extraction: Step III
Aqueous solution of alkaloid salts is
washed with an apolar solvent
(hexane)

Alkalinized with a base using an organic
solvent not miscible with water.

Alkaloids precipitate and dissolve in the
organic phase.

Extraction of aqueous phase continues till
all alkaloids have moved into the
organic phase (tested when Mayers
reaction on the aqueous phase
becomes negative).

This purification step may be carried out
in a separation funnel or in centrifugal
extractors.
















Separation Funnel
Final Step
Organic solvent
containing alkaloid bases
is decanted, freed from
water traces (drying over
anhydrous salt e.g.
sodium sulphate) and
evaporated under
reduced pressure.
A dry residue remains: total
basic alkaloids.









Kava Powder
Alkaloid Extraction in Acidic
Medium
2 Methods possible

Pulverized drug is extracted
directly with acidified water

Or

Pulverized drug is extracted
with acidified alcoholic or a
hydroalcoholic solution.
This is then followed by
distillation under vacuum
(eliminates that alcohol,
leaving behind and acidic
aqueous solution of alkaloid
salts)












Vacuum Distillation
In both cases: Results = aqueous solution of
alkaloid salts needing purification.
Purification achieved by

Alkalinizing solution & extracting bases with an
immiscible organic solvent.

Selectively absorb the alkaloids contained in the
solution on an ion exchange resin, then eluting
them with a strong acid.

Precipitating the alkaloids as iodomercurates.
The resulting alkaloids are recovered by
filtration, dissolved in a mixture of water, alcohol
and acetone and decomposed by passing
through an ion-exchange resin.
Ion-Exchange Resin

Isolation of Alkaloids
All methods of alkaloid
extraction yield impure
compounds, so alkaloids
therefore have to be
separated.
TLC and HPLC are most
commonly used.
Under the best conditions,
alkaloids can be obtained
by direct crystallization:
simply by neutralizing the
acidic extraction medium.










Crystals of Hydrastine
Isolation of Alkaloids
Large-scale extractions may be sent to a
factory for purification & separation
(for cinchona and cocoa alkaloids).

Separation and final purification may be
done using fractional precipitation or
fractional crystallization of salts.

Chromatograpy is used for complex
alkaloids and if only small amounts of
alkaloids are needed.

Volatile liquid alkaloids (nicotine) are
isolated by distillation alkaloid is
distilled off in steam. Nicotine is an
important insecticide, and large
amounts are prepared from the parts
of the tobacco plant which is not used
for tobacco manufacture

Pharmacological Action & Uses
CNS Action: stimulants (caffeine)
or depressants (morphine)
ANS: sympathomimetics
(ephedrine) or sympatholytics
(yohimbine, ergot alkaloids),
parasympathomimetics
(pilocarpine), anticholinergics
(choline), ganglioplegics
(nicotine).
Also: local anesthetics (cocaine),
defibrillation (quinidine), anti-
tumour agents (ellipticine),
anti-malarial (quinine), anti-
bacterials (berberine), and
amoebicides (emetine).




These actions lead to
the extensive use of
alkaloid containing
herbs and drugs.
Although some are
used as galenicals
(belladonna, datura,
and henbane), most
are used as starting
materials for industrial
extraction (morphine
from poppy straw or
opium, and quinine
from Cinchona bark.

Chances Of Having Twins Can Be
Modified By Diet

An obstetrician well known for his care of and research into
multiple-birth pregnancies has found that dietary changes
can affect a woman's chances of having twins, and that her
overall chance is determined by a combination of diet and
heredity. By comparing the twinning rate of vegan women,
who consume no animal products, with that of women who
do eat animal products, Gary Steinman, MD, PhD, an
attending doctor at Long Island Jewish (LIJ) Medical
Center in New Hyde Park, NY, found that the women who
consume animal products, specifically dairy, are five times
more likely to have twins. The study is reported in the May
2006 issue of the Journal of Reproductive Medicine,
available May 20.

The culprit may be insulin-like growth factor (IGF), a
protein that is released from the liver of animals -- including
humans -- in response to growth hormone, circulates in the
blood and makes its way into the animal's milk. IGF
increases the sensitivity of the ovaries to follicle stimulating
hormone, thereby increasing ovulation. Some studies also
suggest that IGF may help embryos survive in the early
stages of development. The concentration of IGF in the
blood is about 13 percent lower in vegan women than in
women who consume dairy.

Biogenesis of Alkaloids
Alkaloids are produced in plants by basic
substances and reactions well-known in
organic chemistry.

Biosynthetic origin cannot be discussed in
general terms for all alkaloids, instead it
has to be covered separately for each of
the major groups of alkaloids
True alkaloids are based on an amino acid (pre-
cursor).
Only a few amino acids form the pre-cursors for all
alkaloids: ornithine, lysine, phylalanine,
tyrosine, tryptophan, histidine and anthranilic
acid.
Alkaloid formation may require the involvement of
only one molecule of amino acid, or 2 molecules
of the same AA, or less commonly, 2 molecules
of different AA or else several molecules of the
same AA.
The formation starts with the formation of a Schiff
base or a Mannich reaction.
When the alkaloid has additional C-atoms, these
play important roles in other metabolic
pathways.

Main Pre-cursors for Alkaloids
a. Group 1: Aliphatic AAs ornithine & lysine
* Pre-cursors to pyrrolidien, piperridine &
tropane alkaloids

b. Aromatic AA Phenylalanine, tyrosine,
tryptophane

c. Precursors of terpenes, steroids & polyketides
often together with the aliphatic or aromatic
AAs result in alkaloids of mixed
biosynthetic origin
Hetrocyclic Alkaloids
Pyrrolidine Alkaloids
Piperridine/pyridine
Pyrrolizidine
Tropane Alkaloids
Quinoline Alkaloids
Isoquinoline Alkaloids
Opium Alkaloids
Aporphine
Norlupinane
Ipecac Alkaloids
Indole Alkaloids
Indolizidine
Imidazole
Purine Alkaloids
Protoalkaloids
Steroidal
Terpenoid

Tropane Alkaloids
Derived from tropine and consist of mandelic,
tropic or benzoic acid esters of tropine.
Are very closely related to each other
All have pronounced physiological actions.

Natural alkaloids include
Hyoscyamine
Hyoscine
Atropine
Cocaine
The above mentioned alkaloids occur within the
Solanaceae family (except cocaine from
Erythroxylaceae family)
Atropine & Hyoscine
Have the same structure differ only in their
optical activity.
Also have different physiological actions
Atropine deadly nightshade, Atropa belladonna:
dilates eye pupils, decreases sweating,
produces stomach acid and saliva & relaxes
smooth muscle (asthma and colic).
Hyoscine black henbane, Hyoscyamus niger:
Limited influence on the CNS. Sedative
Cocaine: Narcotic properties & local anaesthetic
action (e.g. used in eye drops).








Hyoscine
Datura stramonium - Solanaceae
Definition: Stramonium Leaf
consists of the dried
leaves or dried leaves
and flowering tops of
Datura stramonium. The
drug should contain at
least 0.25% alkaloids
calculated as
hyoscyamine.

Common names:
Stramonium leaf,
Thornapple, Jimson or
Jamestown weed

Datura stramonium - Constituents
Main (Tropane) Alkaloids
* Hyoscyamine
Hyoscine (2:1)
Younger plants: hyoscine
predominant alkaloid

Also contains
Atropine

Larger stems contain little
alkaloid, and drug should
contain no more than 3% of
stems with a diameter
>5mm

Datura stramonium Allied Drugs
& Adulterants
ALLIED DRUGS
Datura innoxia
Datura metel (dried
leaves are also curled
and twisted like D.
stramonium), but are
browner in colour.
Datura sanguinea
ADULTERANTS
Xanthium, Carthamus
and Chenopodium
leaves
(easily distinguished
from original herb)
Uses of Datura stramonium
Atropine: Stimulant on CNS
Depresses nerve endings
on the secretory glands
and smooth muscle

Hyoscine: lacks CNS
stimulant action of
atropine
Sedative motion sickness

Atropine & Hyoscine: used
in opthalmic practice to
dilate the pupil of the eye.

Hyoscyamus niger - Solanaceae
Definition: Hyoscyamus
leaf consists of the
dried leaves or dried
leaves and flowering
tops of Hyoscyamus
niger. It should
contain at least 0.05%
alkaloids
hyoscyamine.

Common names:
Henbane
Hyoscyamus niger - Constituents
Tropane Alkaloids
Mainly
Hyoscyamine
Hyoscine (main
constituent)

Hyoscyamus niger Allied Drugs

Hyoscyamus albus
(petiolate stem-leaves
and pale yellow, non-
veined petals bottom
left).
Hyosycamus muticus (top
right)
Hyoscyamus pusillus
Hyoscyamus aureus
Hyoscyamus reticulatus
(Indian henbane bottom
right)
Hyoscyamus niger - Uses
Resembles belladonna
and stramonium in
action only weaker.
Higher hyoscine content
less likely to cause
cerebral stimulation .

Used to relieve spasm
of the urinary tract


Atropa belladonna - Solanaceae
Definition: Belladonna herb
consists of the dried
leaves and flowering tops
of Atropa belladonna,
containing at least 0.3%
alkaloids (hyoscyamine).
Should not contain >3%
stem >5mm in diameter.

USP also allows A.
acuminata in the
Belladonna Leaf
monograph.

Atropa belladonna - Constituents
Main (Tropane) alkaloid
Hyoscyamine

Also contains
Scopoletin
Calcium oxalate

Atropa belladonna
ALLIED DRUGS
Indian belladonna
(Atropa acuminata)
yellow-brown flowers
& brown-green
leaves.
Atropa baetica (yellow
flowers and black
berries) endangered
species
ADULTERANTS
Phytolacca decandra
Ailanthus glandulosa
Atropa belladonna - Uses
Used as a sedative
To stop bodily
secretions (e.g.
saliva)
Root preparations are
used externally


Pyridine Alkaloids
Also referred to as
Pyrrolizidine alkaloids
Include
Lobeline (Lobelia herb)
respiratory stimulant
Used in asthma
preparations.
Nicotine (Nicotiana
tabacum and other
Nicotina spp) toxic
used as an
insecticide



Lobeline






Lobelia inflata- Capmanulaceae
Definition: Lobelia herb
consists of the dried
aerial parts of Lobelia
inflata.

Common Names: Lobelia,
Indian Tobacco)

History: Traditionally used
by the Native Americans
for asthma.

Lobelia inflata Constituents
Contains Pyrrolizidine
Alkaloids
Most important
Lobeline

Also
Lobelidine
Lobelanine
Isolobelanine


Lobelia inflata - Uses
Asthma
Chronic bronchitis
Anti-smoking preparations

Injection of lobeline
hydrochloride is used in
the resuscitation of
newborn infants.

Caution: Toxic doses the
herb has a paralytic
effect.

Quinoline Alkaloids
Consist of alkaloids and
alkaloid salts obtained
from the bark of certain
Cinchona species
(Quinine, Quinidine,
Cinchonine,
Cinchonidine). The
amount of alkaloids
present depend on the
species, environment of
the tree, age, and method
of bark collection.
Quinine: Anti-malarial
Synthetic alkaloids are now
used as substitutes for
quinine for malaria.

Cinchona Bark - Rubiaceae
Definition: Cinchona bark
consists of the various
species races and
hybrids of Cinchona,
large trees indigenous to
Colombia Equador, Peru
& Bolivia

INCLUDES
C. Succirubra, C. calisaya,
C. ledgeriana, C.
officinalis

Cinchona - History
Historically played an
important role in the
treatment of malaria.
This has now lessened
with the introduction of
synthetic drugs.

Traditionally not used by the
native South American
Indians (bitter taste
inspired them with fear).
First used as a medicine
in Peru in 1630 used to
cure fevers.

Cinchona - Constituents
Quinoline Alkaloids
Mainly
Quinine
Quinidine

Also
Quinicine
Cinchonicine
Cinchotannic acid
Anthraquinones

Leaves contain Indole
Alkaloids

Cinchona Chemical Tests
Colour reaction for quinine and quinidine alkaloids

Use bromine and ammonia (the thalleioquin test)

Powdered cinchona is slightly moistened with
glacial acetic acid & heated in an ignition tube

Red drops condense on the sides of the tube.

Cinchona bark therefore gives reactions for
phlobatannins.
Cinchona Allied Drugs
Barks of certain species
of Remijia
e.g. R. pedunculata
R. purdiena
Cinchona Bark - Uses
Bitter tonics
Stomachics
Used as gargles
(tannins in bark
astringent)
Malaria
Prophylaxis of cardiac
arrhythmias
Treatment of atrial
fibrillation

Isoquinoline Alkaloids
Drugs: Opium and Ipecac.
Alkaloids of both these
herbs are in the same
group, yet they differ
chemically and also in
their pharmaceutical
actions.
Opium Alkaloids: morphine,
codeine, ethylmorphine,
thebaine, heroine,
papaverine.
Ipecac Alkaloids: emetine,
cephaeline, psychotrine,
methylpsychotrine








Emetine
Opium Alkaloids Opium
Definition: Opium (Raw Opium) is
the latex obtained by incision
from the unripe capsules of
Papaver somniferum, from the
Papaveraceae Family. It is
dried partially by spontaneous
evaporation and partly by
artificial heat.

Commercially known as Indian
opium.

BP monograph: opium is
intended only as a starting
point for the manufacture of
galenicals, and should not be
dispensed as such.

Papaver somniferum - Constituents
30 Alkaloids
6 main ones
Morphine
Codeine
Thebaine
Noscapine
Narceine
papaverine

Tests for Opium Alkaloids
Morphine: soluble in
sodium hydroxide
(due to phenols)

Codeine is precipitated
by sodium hydroxide.

Other chemical tests
are found in
pharmacopoeias.


Opium - Adulterants
Adulterated with sugary
fruits, gums, powdered
poppy capsules and other
substances.

Adulteration is now useless
(product is first analysed
and the price is paid
depending on the content
of morphine and other
alkaloids)

Papaver somniferum Uses
Opium & Morphine:
Relieve pain
Hypnotics (affect the sensory
nerve cells of the cerebrum).
Opium (closely resembles
morphine) exerts action more
slowly preferable to
morphine (e.g in diarrhoea).
Opium: also a diaphoretic

Codeine
Milder sedative
Relieve cough
Habitual use may cause
constipation

Both Morphine & Codeine
decrease metabolism
Codeine was used to treat
diabetes (before the
introduction of insulin).



Codeine May Be No Cure For
Cough
Researchers at the University of Manchester
North West Lung Centre have found that codeine
- a standard ingredient in cough remedies
could be no more effective than an inactive
placebo compound at treating cough.

Scientists at the Centre, which is based at
Wythenshawe Hospital, studied a sample of
patients with chronic lung disease. After
coughing was induced with citric acid they were
given either codeine or a placebo, and sent
home wearing a lapel microphone to record their
coughing during the day and night.

Lead researcher Dr. Jacyln Smith said: "Codeine
has long been considered the standard anti
cough agent against which others are measured,
but until now little has been known about its
impact in patients with chronic lung diseases.

"
After the placebo therapy the patients' coughing
fell from an average of 8.27 seconds per hour to
7.22 seconds, and after codeine to 6.41
seconds.
"Even though there was a significant reduction
after codeine, from a statistical standpoint there
was really no difference between codeine and
placebo - despite the fact that the dose of
codeine used far exceeds that in over-the
counter cough remedies.

The findings were reported in Journal of Allergy
and Clinical Immunology, and seem to confirm
some medics' view that reductions in coughing
after codeine are attributable to a placebo
effect


Ipecac Alkaloids - Ipecacuanha
Definition: Ipecacuanha
(Ipecacuanha Root) is
the dried root or
rhizome and root of
Cephaelis
ipecacuanha of the
Rubiaceae family.
It should contain at least
2% alkaloids

Ipecacuanha Collection
A pointed stick is used
to lever the plant up
from the ground.
Most of the roots are
then removed.
The plant is replaced
into the ground,
where it will continue t
produce more crops.
Roots are dried in the
sun or by fire and
then transported.

Ipecacuanha Constituents
Ipecac alkaloids
(isoquinoline) alkaloids
Mainly
Emetine
Psychotrine
Cephaeline

Also
Emetamine
Psychotrine methylether
Ipecoside (glycoside)

Ipecacuanha - Adulterants
Other ipecacuanhas,
different roots said to
have emetic
properties.
These are easily
distinguished from the
original root and are
now very rarely
imported.

Test for emetine
Mix 0.5g powdered herb
with 20ml HCL and 5ml
water.
Filter
To 2ml filtrate add 0.01g
potassium chlorate

Result: if emetine is
present, a yellow colour
appears. After standing
for 1hr, changes to red.
Ipecacuanha Uses
Expectorant
Emetic
Amoebic Dysentry

Emetine is more
expectorant and less
emetic in action than
cephaeline

Psychotrine: selective HIV
inhibotors (study could
lead to therapeutically
useful agents)

Indole Alkaloids
These are found in Ergot &
Nux Vormica
Ergot alkloids: based on
lysergic acid (LSD
lysergic acid
diethylamide)
Nux Vormica: 2 important
alkaloids: strychinine
and brucine.
Strychinine: CNS
stimulant, lethal in large
doses (uses as a poison)

Other plants containing indole alkaloids

Rauwolfia serpentina (Indian snakeroot)
Hypertension

Gelsemium sempervirens contains gelsemine,
sempervine.
Used as a CNS depressant used for
migraines.

Catharanthus roseus vinblastine, vincristine.
Used for migraine
Ergot (Ergot of Rye)
Defintion: Ergot (Ergot
of Rye) is the dried
sclerotium of a
fungus, Claviceps
purpurea, arising in
the ovary of the rye,
Secale cereale.

Controlled field
cultivation on rye is
the main source of
crude drug.

Ergot - History
World-wide, sporadic
reports of ergot
poisoning (ergotism)
still appear in
literature: 1992 an
analysis of rye flour
sold in Canada
showed low levels of
fungus contamination.
Of 128 samples, 118
were contained the
fungus.

Ergot - Constituents
Ergot alkaloids
(ergolines)

Include
Ergonovine (water-
soluble) Alkaloids
Ergotoxine &
Ergotamine alkaloids
(water-insoluble)

Ergot Substitutes & Storage
SUBSTITUTES
Ergot of Wheat
Ergot of Oats
Ergot of Diss (reed)

STORAGE
Liable to attacks by insects,
moulds & bacteria.
Dried after collection &
stored in a cool, dry
place. If powdered and
not immediately defatted
looses lots of its
activity. If defatted can
keep for an extended
period.

Traditionally used in
labour to assist the
delivery
Reduce post-partum
haemorrhage

Ergometrine produces
oxyticic effects.



Ergot - Uses
Nux Vormica - Loganiaceae
Definition: Nux vormica
consists of the dried, ripe
seeds of Strychnos nux-
vormica, (a tree growing
up 13m in India, Thailand,
South Vietnam and
Cambodia).

History: in 16
th
Century it
was sold in Europe,
mainly used for poisoning
animals.

Nux Vormica Collection &
Preparation
Fruit consists a berry
about the size of a
small orange.
When ripe it has a hard
orange-yellow
pericarp and a white,
pulpy interior
containing 1-5 seeds.
Seeds are washed to
remove pulp and
dried. Exported in
small sacks known as
pockets.

Nux Vormica - Constituents
2-5% Indole alkaloids

Mainly
Strychine
Brucine

Strychine is more
physiological active
than brucine

Nux Vormica - Uses
Action of the whole drug
resembles the action of
Strychnine
Formerly used as a
circulatory stimulant
(e.g. in surgical shock)
Now used mainly as a
respiratory stimulant (in
certain cases of
poisoning)
Bitter - used to improve
appetite & digestion
Commonly misused as a
General Tonic

Nux Vormica Allied Drugs
Ignatius beans (seeds
of Strychnos ignatii)
fruits are larger than
those of Nux vormica
& may contain up t 30
seeds. Also dark
grey in colour.

Also S. potatorum and
S. nux-blanda
contai no strychnine
or brucine


Rauwolfia serpentine -
Apocynaceae
Defintion: Rauwolfia
consists of the dried
rhizome and roots of
Rauwolfia serpentiana.

(a small shrub found in
India, Pakistan, Java and
Thailand).

Common name: Rauwolfia,
Indian Snakeroot
Rauwolfia - Constituents
30 Alkaloids

Main alkaloid
Reserpine

Also
Rauwolfine
Serpentine
Serpentinine

New alkaloids continue to
be isolated.
Rauwolfia - Uses
Essential Hypertension
Malignant Hypertension
Neuropsychiatric
Disorders
Cardiac arrhythmias
Circulatory Disease



Rauwolfia CAUTIONS!
Conflicting reports on the
possible involvement of
rauwolfia alkaloids in
breast cancer.
Suggested that the alkaloids
do not initiate the
carcinogenic process, but
promote breast cancer
from previously initiated
cells.

DEPRESSION

Protoalkaloids
Alkaloid-like amines.
Have no nitrogen as
part of the hetrocyclic
ring.

Examples: ephedrine
and adrenaline

Both cause dilation of
the bronchi (asthma),
increase heart rate
and peripheral
vasoconstriction.

Ephedra - Ephedraceae
Definition: Various species
of Ephedra are used as a
source of the alkaloids
Ephedrine and
Psuedoephidrine.

These include E. major, E.
intermedia, E. sinica and
E. equisetina.

Common name: Ephedra,
(Ma-huang)

Ephedra - Constituents
Alkaloids
(protoalkaloids)

Mainly
Ephedrine
Pseudoephidrine

Also contains
ephedradines
hypotensive
properties

Ephedra - Uses
Asthma, colds, flu and
Hayfever medications
(action is more prolonged
than adrenaline.
Additional advantage:
need not be given by
injection, but can be
administered orally).
Allopathic: Sinumed (dries
a runny nose)
TCM: Used as an anti-
inflammatory.
Weight loss (increases
metabolism, decreases
appetite CNS stimulant
acts on adrenergic
receptors)
Above ground parts are
normally used, although
the roots are better to use
(less alkaloids)
Ephedra - CAUTIONS
Above-ground parts
contain higher
amounts of alkaloids
(increase BP)

Side Effects: Causes
tremors,
nervousness,
palpitations &
tacchycardia.
Full medical Hx of pt is
required: contra-
indicated in DM,
thyroid disease,
glycoma, all cardiac
conditions (including
hypertension)
Khat or Abyssinian Tea
Consists of the fresh
leaves of Catha
edulis.
Cultivated in Abyssinia
and Arabian
peninsula.
Contains protoalkaloids

Khat Uses and Actions
Traditionally: Fresh leaves are
chewed (mental clarity) and
used in the same way as
cocoa.
Used by students & labourers.

CNS stimulant

Used to treat depression (brings
about a sense of well-being)

Alleviates sensations of hunger
and fatigue.

Elevates mood, increases mental
and physical alertness


Used as a tea: colds & flu, weight
loss, menstrual cramps,
asthma.

Not addictive (leaves are chewed
juice swallowed residue
spat out)

Toxic in high doses
Males: headaches, insomnia, low
sperm count, decreased
fertility
Females: jaundice and acute
gastritis
(Toxic effects differ in males and
females)
Colchicum - Liliaceae
Definition: Colchicum
seed and corm are
derived from the
Autumn crocus or
meadow saffron,
Colchicum
autumnale.


Colchicine
Constituent in colchium
seeds and corm.
Amorphous, yellow-white
alkaloid (darkens on
exposure to light).
Gives a strong yellow
coloration with strong
mineral acids.
Dissolves readily in water,
alcohol and chloroform,
but only slightly in ether
or petroleum spirit.
Weak base
Colchium Uses
Relieve gout (used with
caution professional
supervision)
Also used in biological
experiments to
produce polyploidy
(multiplication of the
chromosomes in a
cell nucleus)
Purine Alkaloids
Also known as non-alkaloids (xanthines)
* synthetic origin does not contain an intact AA
* Amphoteric Character
* Peculiar solubility in warm water and in chlorinated
solvents.

Examples are caffeine (seeds of coffee plants, kola
plants, tea leaves and guarana seeds),
theobromine (Theobroma cocao) and theophylline
(tea leaves & cola nuts).
Beverages such as tea and coffee owe their stimulant
action to the purine alkaloids.
Caffeine: stimulates CNS
and has a weak diuretic
action.
Theobromine: opposite
action.
Theophylline: relaxes
involuntary muscles
more effectively than
caffeine or theobromine
Caffeine does not
precipitate like most
alkaloids.
A purple colour is derived
from caffeine and other
purine derivatives
(murexide test).

Pharmacological Activity of
Caffeine
CNS activity, enhances
alertness, facilitates thought
formation, decreases the
sensation of fatigue.
Very high doses: induces
nervousness, insomnia &
tremors.
Stimulates respiratory centre of
the brain (increasing
sensitivity to CO2).
Cardiovascular activity:
Positive inotropic action,
causes tacchycardia,
increases CO, slight
peripheral dilation, mild
diuretic action

Caffeine: Uses
In combinations with
antipyretics and
analgesics, cold and
flu medication.
(increases the intestinal
absorption of some of
these drugs; or to
counteract
drowsiness).
Ingredient in non-
alcoholic beverages
and energizing
beverages

Caffeine Side Effects
Sinus tacchycardia
Epigastric pain
Nausea
Vomiting
Headaches
Nervousness
Insomnia
tremors


Pharmacological Action of
Theophylline
bronchial smooth muscle
relaxant
Stimulates respiratory
centre in the brain stem
by increasing sensitivity
to CO2.
CNS stimulating
Slightly inotropic.
Diuretic activity is stronger
than that of caffeine.


Theophylline - Uses
Used for cough &
asthmatic medication
Reversible
bronchospasm
(chronic obstructive
pulmonary disease).

Theophylline Side Effects
Nervousness
Sleeplessness
Transient tacchycaridia
Permanent tacchycardia
Nausea
Vomiting
Headaches
Tremors
Diarrhoea


Theobroma Actions

Found in Cocoa
Nutritive/food
Nervous system
stimulant
Diuretic


Theobroma - Uses
Cocao butter is used as
a base for
suppositories and
salves

Heart and kidney tonic

Chocolate (flavouring)