ALKALOIDAL

AMINES
Subject name: PHARMACOGNOSY-4
Subject code: 250006
DR. HARISHKUMAR N. KAKRANI,
PRICIPAL,
C. V. M INSTITUTE OF DEGREE COURSE IN
PHARMACY (institute code: 272),
VALLABH VIDYANAGAR 388 121

ALKALOIDS

Alkaloids are a group of naturally occurring organic substances, having nitrogen in their heterocyclic ring.
o

Except few i.e. proto- and pseudo-alkaloids that do not have nitrogen in their structural rings.

Most alkaloids contain oxygen; those compounds are usually colorless crystals at ambient conditions.

Oxygen-free alkaloids, such as nicotine or coniine are typically volatile, colorless, oily liquids.

Some alkaloids are colored, like berberine (yellow) and sanguinarine (orange).

Most alkaloid are weak bases, but some are amphoteric, for example theobromine and theophylline.

Most alkaloids are poorly soluble in water but readily dissolve in organic solvents, such as diethyl

ether, chloroform and 1,2-dichloroethane.

o

However, caffiene dissolves well in boiling water.

With acids, alkaloids form salts of various strengths.

o

Those salts are usually soluble in water and alcohol and poorly soluble in most organic solvents.

Exceptions include scopolamine hydrobromide which is soluble in organic solvents and water-soluble
quinine sulfate.

Alkaloids occur as free bases, salts or N-oxides (NO). When the salt of an alkaloid is treated with
hydroxyl ion, nitrogen gives up a hydrogen ion and the free amine is liberated.
Alkaloidal amines, Dr. Harish Kakrani, CDCP

ALKALOIDS

May be of plant or animal origin

Nitrogen of alkaloids: The Nitrogen atom can either be 1, 2, 3 or 4 (quaternary).

Alkaloids are usually bitter in taste.

They are optically active.

Generally the levo rotatory isomer l (-) is pharmacologically more active than the dextro rotatory
isomer d (+) of the same alkaloid.

Exception: d(+) pilocarpine, d(+) tubocurarine and d(+) quinidine are medically used.

Alkaloids are pharmacologically active even in microgram quantities.

Plant alkaloids usually have profound physiological actions in humans even in microgramme
quantity with nervous system effects being the most prominent.

Examples of some of the more dramatic actions of alkaloids are:

Analgesics/ narcoticsmorphine

Mydriaticsatropine

Mioticspilocarpine

Hypertensivesephedrine

Hypotensivesreserpine

Bronchodilatorlobeline

Stimulantsstrychnine

Antimicrobialsberberine

Antileukemicvinblastine

BIOGENESIS OF ALKALOIDS:
o

Alkaloids are produced in plants by basic substances and reactions well-known in organic
chemistry.
Alkaloidal amines, Dr. Harish Kakrani, CDCP

BIOGENESIS OFALKALOIDS

True alkaloids are based on an amino acid (pre-cursor). Only a few amino acids form the precursors for all alkaloids: ornithine, lysine, phylalanine, tyrosine, tryptophan, histidine and
anthranilic acid.

Alkaloidal amines, Dr. Harish Kakrani, CDCP

OCCURRENCE & DISTRIBUTION 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 biogenetic 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.

Alkaloidal amines, Dr. Harish Kakrani, CDCP

CLASSIFICATION OF ALKALOIDS

ALKALOIDS

Proto-alkaloids
(AMINO- ALKALOIDS)

True Alkaloids

Pseudo-alkaloids

Nitrogen in its
heterocyclic ring system

Have no nitrogen as a
part of their heterocyclic
ring

These alkaloids have

heterocyclic ring with
nitrogen in it

Derived from amino

acids

Derived from amino

acids

But these are not

derived from amino
acids

Alkaloidal amines, Dr. Harish Kakrani, CDCP

CLASSIFICATION OF TRUE ALKALOIDS

Sr. No.

Class

Pyridine/
piperidine

Tropane

Examples

Species

Pharmacological actions

Nicotine

Nicotiana tabacum

Adrenergic, CNS stimulant

Lobeline

Lobelia inflata

Expectorant, bronchodilator

Piperine

Piper nigrum
P. longum

Stimulant
hepatoprotective

Arecoline

Areca catechu

Vermicide, taenifuge

Hyoscyamine

Atropa belladonna

Anticholinergic, Antisialagogue

Cocaine

Erythroxylon coca

CNS stimulant, anaesthetic,

narcotic

Scopalamine

Datura metel

Anticholinergic, CNS depressant

Quinine

Cinchona spp.

Antimalarial, Antiarrhythmia

Quinoline

Isoqinoline

Quinidine

Berberine

Berberis spp.

Antimicrobial, antiprotozoal,
cholagogue

Morphine

Papaver somniferum

Sedative, analgesic, Narcotic

Chelidonine

Chelidonium majus

Spasmolytic, cholagogue

Boldine

Pneumus boldo

Spasmolytic, choleretic

Emetine

Cephaelis Ipecacuanha

Emetic

Alkaloidal amines, Dr. Harish Kakrani, CDCP

Cardioactive

CLASSIFICATION OF TRUE ALKALOIDS

Sr.
No.

Class

Quinolizidine

Pyrrolizidine

Indole

Imidazole

Examples

Species

Pharmacological actions

Sparteine

Sarothamnus
scoparius

Oxytocic, cardiotonic, diuretic

Sececionine
Symphytine

Senecio jacobeae
Symphytum spp.

Hepatotoxin

Reserpine

Rauwolfia serpentina

Sedative, Antihypertensive

Ergotamine

Claviceps purpurea

Vasoconstrictor, hypertensive

Strychnine

Strychnos nuxvomica

CNS stimulant, deadly toxin

Yohimbine

Aspidosperma quebracho

Aphrodisiac, stimulant

Pilocarpine

Pilocarpus jaborandi

Miotic, cholinergic

CLASSIFICATION OF PROTOALKALOIDS
Sr. No.

Class
Alkaloidal
amines
(protoalkaloids)

Examples

Species

Pharmacological actions

Colchicine

Colchicum autumnale

Antimitotic, uric acid amines

solvent

Ephedrine

Ephedra sinica

Sympathetic stimulant,
bronchodilator

Mescaline

Lophophora williamsii

Hallucinogenic

Alkaloidal amines, Dr. Harish Kakrani, CDCP

CLASSIFICATION OF PSEUDO-ALKALOIDS

Sr. No.

Class

Purine
alkaloids

Steroidal
alkaloids
Terpenoidal
alakaloids

Examples

Species

Pharmacological actions

Caffeine

Coffea arabica

CNS and sympathetic stimulant

Theophylline

Thea sinensis

Bronchodilator, diuretic

Guaranine

Paullinia cupana

CNS and sympathetic stimulant

Solanine

Solanum spp.

Steroid precursors, antiinflammatory

Veratrine

Veratrum album

Cardiac depressants,
antihypertensives

Aconitine

Aconitum spp.

Antipyretic, analgesic, neurotoxin

Alkaloidal amines, Dr. Harish Kakrani, CDCP

AMINO-ALKALOIDS
(PROTO-ALKALOIDS)

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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AMINO ALKALOIDS
GENERAL CHARACTERISTIC FEATURES:

Protoalkaloids

Have no nitrogen as the part of the heterocyclic ring.

Derived from amino acid like l- phenyl alanine.

Physiologically active compounds

Example: Ephedrine (Ephedra species) and Colchicine (Colchicum autmnale)

BIOSYNTHESIS OF AMINO ALKALOIDS:

Amino alkaloids are derived from amino acid l- phenyl alanine through shikkimic acid pathway.

The pathway finds its route from carbohydrates for the biosynthesis of C6- C3 units (i.e. phenyl
propane derivatives) like phenyl alanine and tyrosine

An important branching point arises at chorismic acid, which acts as a precursor for different amino
acids.

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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BIOSYNTHESIS OF AMINO ALKALOIDS

Dehydration

3- dehydro
Shikimic acid

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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BIOSYNTHESIS OF AMINO ALKALOIDS

Shikimic
acid
Prephenic
acid
Dehydration

Phenyl pyruvic acid

Phosphoenol
pyruvic acid

Shikimic acid3- phosphate

5- enolpyruvyl
shikimate-3phosphate
Alkaloidal amines, Dr. Harish Kakrani, CDCP

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BIOSYNTHESIS OF AMINO ALKALOIDS

Phenyl alanine

Ephedrine
(Ephedrine spp.)

Colchicine
(Colchicum
autumnale)
Alkaloidal amines, Dr. Harish Kakrani, CDCP

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GENERAL PHARMACOLOGICAL ACTION & USES OF AMINO- ALKALOIDS

Cause

Dilation of the bronchi (asthma),

Increase heart rate and

Peripheral vasoconstriction

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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EPHEDRA

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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EPHEDRA

Synonym: Ma-Huang.

Biological source: It consists of dried young stems of Ephedra gerardiana (wall.) Stapf, and E. nebrodensis
(Tineo) Stapf.
o

Family: Gnetaceae (Ephedraceae).

Ephedra should contain not less than 1% of total alkaloids, calculated as ephedrine.

Geographical source: China, Pakistan, North-west parts of India, Australia, Kenya, Spain & Yugoslavia.

Cultivation, Collection & preparation:

o

Cultivated at an altitude of 2500- 3000 m.

Annual rainfall should not exceed 50cm.

Propagated by seeds or by layers or divisions of root stock.

Seeds sown early in spring at a distance of 5cm, keeping distance of 1 mt between 2 rows

Collected after attaining the age of 4 yrs for extraction of alkaloid

Alkaloid content varies from season to season.

It is maximum in autumn

Twigs dried in sun or even by artificial ways.

Stored in dry & well closed containers

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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EPHEDRA

Macroscopic Characters:
o General appearance: Thin cylindrical or ellipsoidal cylinder,
o Size: 12 mm in diameter; 3.55.5cm in length of internode;
o Color: Light green to yellow-green;

o Surface: numerous parallel vertical furrows on the surface; scaly leaves at the node
portion;
o Leaves: 24 mm in length, light brown to brown in colour, usually opposite at every
node, adhering at the base to form a tubular sheath around the stem.

o Transverse section of the stem: appears as circle and ellipse, the outer portion
greyish green to yellow-green in colour, and the centre filled with a red-purple
substance or hollow.
o Fracture at an internode: the outer part is fibrous and easily split vertically

o Odour: slight;
o Taste: slightly bitter and astringent, giving a slight sensation of numbness on the
tongue .

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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EPHEDRA

Macroscopical characteristics
of
Ephedra Stem
&
Leaves

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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EPHEDRA

Microscopic characteristics:
1.

STEM:
The epidermal cells of the stem covered with a moderately thick granular cuticle; the cells are
polygonal or subrectangular, axially elongated, having straight anticlinal walls.
The stomata are few and are of the ranunculaceous type with lignified appendages.

Cortical parenchyma and pith cells contain an amorphous reddish brown substance.
Non-lignified or lignified hypodermal and pericyclic fibres, which have thick walls, bear slit-like pits
and blunt, slightly tapering, occasionally forked ends.
The vessels of the secondary xylem of the stem are lignified with bordered pits, having rounded or
oval apertures.
Few, small, rounded, simple and compound starch granules with indistinct hilum are present in
cortical parenchyma, pith, and medullary ray cells.
Few, small prisms of calcium oxalate are present in the cortical parenchyma.
2.

LEAF:

The epidermis of the scaly leaf is covered with smooth (upper) or warty (lower) cuticle and consists
of subrectangular to polygonal cells, having straight or sometimes slightly beaded anticlinal walls;
few stomata are present resembling those of stem.
Alkaloidal amines, Dr. Harish Kakrani, CDCP

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EPHEDRA
The epidermis of the apical and marginal regions of the scaly leaf shows short papillae-like
outgrowths.
Chlorenchymatous palisade-like cells form the outer zone of the cortex; rounded ordinary
parenchymatous cells form the inner zone of the cortex.
The fibres of the scaly leaf are lignified.

Powder characteristics:
o

Powdered herb is greyish green.

The characteristics observed are as follows:

Thick fragments of cutinized outer walls of epidermis
Sclerenchyma fibres with extremely thickened, non-lignified to lignified walls, narrow, frequently

indistinct lamina and sharp pointed ends.

Fragments of vascular tissue showing spiral and pitted tracheae.
Fragments of epidermis with sunken elliptical stomata

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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EPHEDRA

Transverse Section of Ephedra Stem

Powder characteristics of Ephedra stem

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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EPHEDRA

Chemical constituents:
o

Amino alkaloids: Ephedrine, nor-ephedrine, n-methyl ephedrine, pseudo-ephedrine.

Chemically, ephedrine is 1-phenyl-1- hydroxy-2- methylaminopropane

Soluble in water, alcohol, organic solvents and oil
Odourless & colourless
Deliquescent
Decomposes when exposed to air.

Other constitutents:

Macrocyclic alkaloids- ephedradines present in roots.

Oxazolidone.

Ephedrine

Nor-ephedrine
N-methyl ephedrine
Alkaloidal amines, Dr. Harish Kakrani, CDCP

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EPHEDRA

Chemical Tests:
o

Ephedrine dissolved in water & dil. HCl

Violet colored solution

treat individually with Copper sulfate & NaOH

if shaken with solvent ether, organic layer shows purple color & aqueous

layer shows blue color.

Uses:
o

Sypathomimetic effects

Bronchodilator in asthma

In treatment of allergic conditions like hay fever

As compared to adrenaline onset of action for ephedrine is slow, but effect is much prolonged, as it is not
quickly hydrolysed by mono amine oxidase in the body.

Causes peripheral contraction of arterioles, therefore used to correct the low blood pressure conditions.

Allied drugs:
o

Genus Ephedra has about 45 species

About 25 species contain ephedrine.

Prominent species containing ephedrine are E. equisetina & E. sinica

E. intermedia, E. major, E. helryetica & E. alata: Contain from 35- 87% of ephedrine in total alkaloids.

The other plants containing ephedrine are Aconitum napelles (Ranunculaceae); Sida cordifolia; and S.
rhombifolia (Malvaceae); Roemeria refracta (Papaveraceae) and Taxus baccata (Taxaceae).

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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COLCHICUM

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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COLCHICUM

Synonyms: Meadow saffron seeds, autumn crocus

Botanical source : It consists of dried ripe seeds and fresh or dried sliced corms of Colchicum autumnale
o

Family: Liliaceae.

Geographical sources:
o

Indigenous to Britain

Grows in Central and Southern Europe

Cultivation & Collection:

o

Colchicum propagates by repeating the life cycle with the corm, which is present as a swollen
underground stem with sheathing leaves.

Towards the end of summer, the fully grown corm develops daughter corms in the axil of scaly leaf
near the base.

These daughter corms develop parasitically on parent corm & subsequently parent corm withers away.

The daughter corms develop into new corms.

May also be propagated by seeds, sown 1/8 inch deep in a bed of fine soil outdoors in August or
September; transplanting seedlings 3 inches apart when two years old; or by division of bulbs in

August. Seedling bulbs do not flower till four or five years old.
Alkaloidal amines, Dr. Harish Kakrani, CDCP

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COLCHICUM

Macroscopic characteristics:
1. Colchicum seeds:
o

Very hard in nature

Have a projection at hilum & from there

develops strophiole, which is an outgrowth of testa.

Size: 2-3mm in diameter

Taste: bitter & acrid

Odour: Odourless

2. Colchicum corm:
o

Size: 2-3cm in diameter, 2-5mm thickness

Fracture: Short

Shape: sub-reniform or ovate in outline

Color: yellowish brown

Taste: bitter

Odour: Odourless
Alkaloidal amines, Dr. Harish Kakrani, CDCP

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COLCHICUM

Microscopic characters:

1.

T.S of Seed:

2.

Shows parenchyma & endosperm

Parenchymatous cells are reddish brown with thick walls

Endospermic cells show pitted walls & contain aleurone grains and fixed oils

Strophiole portion of the seeds contain starch

T.S of corm:

Corm has epidermis, parenchyma & vascular tissue

Parenchymatous cells have abundant starch grains

Epidermis has circular stomata

In vascular part, the xylem vessels are spiral or annular.

Chemical Constituents:
o

SEED: 0.2-1% amino alkaloid , of which Colchicine is 0.8%

CORMS: 0.6% Colchicine. Also contains demecolcine

Both the alkaloids contain tropolone or cycloheptatrien-ol-one ring structure.

Colchicine is a toxic, yellowish-white amorphour or crystalline substance that darkens on exposure

to light. It is soluble in alcohol & chloroform, sparingly soluble in water.
Alkaloidal amines, Dr. Harish Kakrani, CDCP

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COLCHICUM

Powder characteristics of Colchicum seed powder

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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COLCHICUM

Demecolcine

Colchicine

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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COLCHICUM

Chemical tests:
o

Colchicine + 60 - 70% sulphuric acid or conc. HCl

yellow colour is produced.

Alcoholic solution of colchicine + ferric chloride

red color

Uses:
o

Gout & rheumatism

Also possesses anti-tumor activity

Used in horticulture as a chemical agent for bringing polyploidy

Allied drugs:
o

Plants bearing chemical contents similar to colchicine type of alkaloids belong to different
genera such as, Dipidax, Gloriosa, Androcybium, Camptorrhiza, etc.

Other genera of same family liliaceae which contain colchicine- Androcybium, Bulbocodium,
Dipidax, Littonia, Fritillaria, Ornithoglossum, etc.

Alkaloidal amines, Dr. Harish Kakrani, CDCP

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