ALKALOIDS

ALKALOIDS: Typical alkaloids are derived from plant sources, they are basic, they contain
one or more nitrogen atoms (usually in a heterocyclic ring) and they usually have a marked
physiological action on man or other animals. The name ‘proto-alkaloid’ or ‘amino-alkaloid’ is
sometimes applied to compounds such as hordenine, ephedrine and colchicine which lack one
or more of the properties of typical alkaloids. Other alkaloids, not conforming to the general
definition, are those synthetic compounds not found in plants but very closely related to the
natural alkaloids (e.g. homatropine).

The names of the alkaloids are obtained in various ways: (1) from the generic name of the plant
yielding them (hydrastine, atropine), (2) from the specific name of the plant yielding them
(cocaine, belladonine, (3) from the common name of the drug yielding them (ergotamine), (4)
from their physiologic activity (emetine, morphine), and (5) occasionally from the discoverer
(pelletierine).

Alkaloids usually contain one nitrogen atom, although some, like ergotamine, may contain up to
5. The nitrogen may exist as a primary amine (RNH3) as a secondary amine (R2NH), or as a
tertiary amine (R3N).

Some of the functions- (1) poisonous agents protect the plant against insects and herbivores, (2) end
products of detoxification reactions representing a metabolic locking-up of compounds otherwise
harmful to the plant (3) regulatory growth factors, or (4) reserve substances capable of supplying
nitrogen or other elements necessary to the plant's economy.

PROPERTIES: Most alkaloids are well-defined crystalline substances which unite with acids
to form salts. In the plant they may exist in the Free State, as salts or as N-oxides. In addition to
the elements carbon, hydrogen and nitrogen, most alkaloids contain oxygen. A few, such as
coniine from hemlock and nicotine from tobacco, are oxygen-free and are liquids. Although
coloured alkaloids are relatively rare, they are not unknown; berberine, for example, is yellow
and the salts of sanguinarine are copper-red. Knowledge of the solubility of alkaloids and their
salts is of considerable pharmaceutical importance. Not only are alkaloidal substances often
administered in solution, but also the differences in solubility between alkaloids and their salts
provide methods for the isolation of alkaloids from the plant and their separation from the non-
alkaloidal substances also present. While the solubilities of different alkaloids and salts show
considerable variation, as might be expected from their extremely varied structure, it is true to
say that the free bases are frequently sparingly soluble in water but soluble in water but soluble
in organic solvents; with salts the reverse is often the case, these being usually soluble in water
but sparingly soluble in organic solvents. For example, strychnine hydrochloride is much more
soluble in water than is strychnine base. It will soon be realized that there are many exceptions
to the above generalizations, caffeine (base) being readily extracted from tea with water and
colchicine being soluble in acid, neutral or alkaline water. Again, some alkaloidal salts are
sparingly soluble—for example, quinine sulphate is only soluble to the extent of 1 part in 1000
parts of water, although 1 part quinine hydrochloride is soluble in less than 1 part of water.

CLASSIFICATION: Alkaloids are usually classified according to the nature of the basic
chemical structures from which they derive. Arecoline, lobeline, and nicotine are derivatives of
pyridine and piperidine; atropine, hyoscyamine, and hyoscine are derived from tropane, a
condensation product of pyrrolidine and piperidine; the cinchona alkaloids, quinine, quinidine,
cinchonine, and cinchonidine, contain quinoline as the principal nucleus; hydrastine, (+)-
tubocurarine, emetine, and the opium alkaloids are characterized by the isoquinoline nucleus.
Other types include ergonovine, reserpine, and strychnine, which derive from the indole ring;
pilocarpine, which has the imidazole ring; caffeine and theobromine, which are purine bases, and
protoveratrine, which contains a steroidal structure.

Various schemes for the classification of alkaloids have been suggested. The following plan is
based on the ring structure or nucleus of the chief alkaloid group in the plant drug: (1) pyridine-
piperidine combined, (2) tropane (3) quinoline (4) isoquinoline, (5) indole, (6) imidazole, (7)
steroid, (8) alkaloidal amine, and (9) purine.

 Bufo marinus accumulates huge amount of morphine.

 PROTOALKALOIDS/ AMINOALKALOIDS: Those alkaloid-like amines which do not

have the nitrogen as part of a heterocyclic ring system are often termed protoalkaloids. They are
not restricted to any particular class of alkaloids and are often classified according to the amino
acids from which they are derived. Some are quaternary bases as, for example, the
protoberberine alkaloids which constitute a large group with diverse structures and a wide
distribution in nature. Although not prominent in common herbal drugs the alkaloids are being
studied for their antibacterial, antimalarial and potential genotoxic properties.

 SYNTHETIC ALKALOIDS: These are not found in plants, but very closely related
to natural alkaloids. Eg: Homatropine, etc.

STUCTURE & CLASSIFICATION: Alkaloids show great variety in their botanical and
biochemical origin, in chemical structure and in pharmacological action. There are two broad divisions: I.
Non-heterocyclic or atypical alkaloids, sometimes called ‘proto-alkaloids’ or biological amines. II.
Heterocyclic or typical alkaloids, divided into 14 groups according to their ring structure.
 TYPE EXAMPLES
A. Non- heterocyclic  Hordenine or N-  In germinating
alkaloids methyltyramine barley
 Mescaline  Lophophora
williamsii
 Ephedrine  Ephedra

 Colchicine  Colchicum
 Jurubin  Solanum
paniculatum
 Taxol  Taxus brevifolia

B. Heterocyclic alkaloids 1. Pyrrole and pyrrolidine

‘ Eg:
 Hygrines  Coca spp.
 Stachydrine  Stachys tubifera
(Labiatae)
2. Pyrrolizidine
Eg:
 Symphitine,  Symphytum
echimidine
 Senecionine,  Senecio
seneciphylline

3. Pyridine and piperidine

Eg:
 Trigonelline  Fenugreek
 Coniine  Conium maculatum
 Arecoline  Areca catechu
 Piperine  Piper spp.

4. Tropane (piperidine/N-
methyl-pyrrolidine)
Eg:
 Hyoscyamine  Hyoscyamus
 Atropine  Atropa
 Cocaine  Coca spp
 Pseudo-pelletierine  Punica granatum
5.Quinoline
Eg:
 Quinine, quinidine,  Cinchona
cinchonine,
cinchonidine

6. Isoquinoline
Eg:
 Papaverine  Papaver
somniferum
 Erythraline  Erythrina spp

 Morphine, codeine  Papaver

somniferum

7. Aporphine (reduced
isoquinoline/ naphthalene)
 Boldine
 Peumus boldus
8. Quinolizidine
 Sparteine, cytisine,
lupanine, laburnine  Sometimes called
‘the lupin
alkaloids’. Occur
particularly in the
Leguminosae,
subfamily
Papilionaceae, e.g.
broom. Cytisus
scoparius; dyer’s
broom, Genista
tinctoria; Laburnum
and Lupinus spp.

9. Indole or benzopyrrole
 Ergometrine,  Claviceps spp
ergotamine
 Lysergic acid amide  Rivea corymbosa
  Ajmaline,
serpentine,  Rauwolfia
reserpine serpentine
 Vinblastine,
vincristine  Catharanthus
 Strychnine, brucine roseus
 Strychnos
10. Indolizidine
Eg:  Castanospermum
 Castanospermine austral

 Swainsonine  Swainsona spp

11. Imidazole or
glyoxaline
Eg:
 Pilocarpine  Pilocarpus spp

12. Purine
(pyridimine/imidazole)
Eg:
 Caffeine  Tea,coffee
 Theobromine  Cocoa

13. Steroidal
Eg:
 Solanidine  Shoots of potato
 Veratrum  Veratrum spp
 Conessine  Holarrhena
 Funtumine  Funtumia elastica

14. Terpenoid
Eg:
 Aconitine, atisine  Aconitum and
and lyctonine,etc. Delphinium, etc.
A. TROPANE ALKALOIDS:

1. STRAMONIUM LEAF: -

 SOURCE: Stramonium Leaf BP/EP (Thornapple Leaves; Jimson or

Jamestown Weed) consists of the dried leaves or dried leaves and flowering
tops of Datura stramonium L. and its varieties (Solanaceae). The drug is
required to contain not less than 0.25% of alkaloids calculated as
hyoscyamine. The plant is widespread in both the Old and New Worlds.
British supplies are derived mainly from the Continent (Germany, France,
Hungary, etc.).
 CONSTITUENTS:
 Stramonium usually contains 0.2–0.45% of alkaloids, the chief of
which are hyoscyamine and hyoscine, but a little atropine may be
formed from the hyoscyamine by racemization.
 At the time of collection these alkaloids are usually present in the
proportion of about two parts of hyoscyamine to one part of hyoscine.
 In young plants hyoscine is the predominant alkaloid.
 USES:
 Atropine has a stimulant action on the central nervous system and
depresses the nerve endings to the secretory glands and plain muscle.
 Hyoscine lacks the central stimulant action of atropine; its sedative
properties enable it to be used in the control of motion sickness.
 Hyoscine hydrobromide is employed in preoperative medication,
usually with papaveretum, some 30–60 min before the induction of
anaesthesia.
 Atropine and hyoscine are used to a large extent in ophthalmic
practice to dilate the pupil of the eye.

2. BELLADONNA LEAF:-

 SOURCE:- Belladonna Leaf BP/EP (Belladonna Herb) consists of the

dried leaves and, occasionally fruit-bearing flowering tops of Atropa
belladonna L. (Solanaceae); it contains not less than 0.30% of total alkaloids
calculated as hyoscyamine.
  CONSTITUENTS:- The drug from A. belladonna contains 0.3–0.60% of
alkaloids, the chief of which is hyoscyamine. Small quantities of volatile
bases, such as pyridine and N-methylpyrroline, are present, and if not
removed during the assay of the drug by heating, increase the titration and
appear in the result as hyoscyamine. The leaves also contain a fluorescent
substance, β-methylaesculetin (scopoletin), and calcium oxalate. They yield
about 14% of ash and not more than 4% of acid insoluble ash.
 USES:-
 Belladonna leaves are mainly used for internal preparations which are
used as sedatives and to check secretion. Preparations of the root are
mainly used externally.

3. BELLADONNA ROOT:-

 SOURCE:- Belladonna root consists of the dried roots or rootstock and

roots of Atropa belladonna (Solanaceae).
 CONSTITUENTS: - Atropa belladonna root contains about 0.4–0.8% of
alkaloids calculated as hyoscyamine. Samples of belladonna root examined
by Kuhn and Schäfer showed 0.3–1.0% of alkaloids, of which 82.8–97.3%
was hyoscyamine, 2.7– 15.2% atropine, and 0.0–2.6% scopolamine.

4. COCA LEAF AND COCAINE: -

 SOURCE: - Coca leaves are derived from two cultivated shrubs of the
Erythroxylaceae, namely Erythroxylum coca Lam. and E. novogranatense
(Morris) Hieron.

 CONSTITUENTS:- Coca leaves contain about 0.7–1.5% of total alkaloids,

of which cocaine, cinnamylcocaine and α-truxilline are the most important.
They occur in different proportions in different commercial varieties.
Javanese leaves are usually richest in total alkaloids, of which the chief is
cinnamylcocaine, while the Bolivian and Peruvian leaves contain less total
alkaloid but a higher proportion of cocaine. Other substances isolated from
various varieties of the leaves are hygrine, hygroline, cuscohygrine,
dihydrocuscohygrine, tropacocaine (3β-benzoyloxytropane), crystalline
glycosides and cocatannic acid. 1-Hydroxytropacocaine (free hydroxyl
 situated at a bridgehead carbon) has been isolated as a major alkaloid of
greenhouse-cultivated E. novogranatense var. novogranatense; much lower
amounts were detected in var. truxillense and in field cultivated coca from
Colombia and Bolivia.

 USES: - Cocaine and its salts were the earliest of the modern local
anaesthetics but, because of their toxic and addictive properties, their use is
now almost entirely confined to ophthalmic, ear, nose and throat surgery.

B. QUINOLINE ALKALOID DRUGS:-

1. CINCHONA:-

 SOURCE:- Cinchona bark consists of various species, races and hybrids of

Cinchona (Rubiaceae), large trees indigenous to Colombia, Ecuador, Peru
and Bolivia. The BP/EP recognizes the whole or cut, dried bark of Cinchona
pubescens Vahl (C. succirubra Pavon), C. calisaya (Weddell), of C.
ledgeriana (Moens ex Trimen) or its varieties or hybrids, containing not less
than 6.5% of total alkaloids, 30–60% of which consists of quinine-type
alkaloids. The former importance of cinchona bark and its alkaloids in the
treatment of malaria has been lessened by the introduction of synthetic
drugs, but it remains of great economic importance, and salts of quinine and
quinidine are included in most pharmacopoeias.
 CONSTIUENTS:- Cinchona bark contains quinoline alkaloids (see Fig.
26.34). The principal alkaloids are the stereoisomers quinine and quinidine
and their respective 6′-demethoxy derivatives, cinchonidine and cinchonine.
The alkaloids appear to be present in the parenchymatous tissues of the bark
in combination with quinic acid and cinchotannic acid. Quinic acid (see Fig.
19.5) is present to the extent of 5–8%. Cinchotannic acid is a phlobatannin
and a considerable amount of its decomposition product, ‘cinchona red’, is
also found in the bark. Other constituents are quinovin (up to 2%), which is
a glycoside yielding on hydrolysis quinovaic acid and quinovose
(isorhodeose).
 USES:-
 Galenicals of cinchona have long been used as bitter tonics and
stomachics.
 On account of the astringent action, a decoction and acid infusion are
sometimes used as gargles. Before World War II, quinine was the
drug of choice for the treatment of malaria but became largely
superseded by the advent of synthetic antimalarials developed during
that period. It has, however, remained of importance in Third World
countries and has re-emerged as suitable for the treatment of
Plasmodium falciparum infections (falciparum malaria) in the many
areas where the organism is now resistant to chloroquine and other
antimalarials.
 Quinidine is employed for the prophylaxis of cardiac arrhythmias and
for the treatment of atrial fibrillation; it also has antimalarial
properties and like quinine is effective against chloroquine-resistant
organisms.