Alkaloids

Definition:
“Alkaloids are a class of basic, naturally occurring Heterocyclic Nitrogenous
organic compounds (Containing at least one nitrogen atom), of plant origin that is
physiologically active.”
Introduction:
One of the largest groups of chemicals produced by plants is the alkaloids. Many of these metabolic
by-products are derived from amino acids and include an enormous number of bitter, nitrogenous
compounds. More than 10,000 different alkaloids have been discovered in species from over 300
plant families. Alkaloids often contain one or more rings of carbon atoms, usually with a nitrogen
atom in the ring. The position of the nitrogen atom in the carbon ring varies with different alkaloids
and with different plant families. In some alkaloids, such as mescaline, the nitrogen atom is not within
a carbon ring. In fact, it is the precise position of the nitrogen atom that affects the properties of these
alkaloids. These compounds are renowned for their potent pharmacological activities. Whilst tiny
amounts of some can immobilize an elephant or a rhinoceros, others have important clinical use, such
as analgesics, antimalarial, antispasmodics, for pupil dilation, treatment of hypertension, mental
disorders and tumours. They are all nitrogen heterocycles which occur mainly in plants as their salts
of common carboxylic acids, such as citric, lactic, oxalic, acetic, maleic and tartaric acids as well as
fumaric, benzoic, aconitic and veratric acids. Their amine character produce an alkaline solution in
water and hence the origin of their name—alkaloids. Although they undoubtedly existed long before
humans, some alkaloids have remarkable structural similarities with neurotransmitters in the central
nervous system (CNS) of humans, including dopamine, serotonin and acetylcholine. The amazing
effect of these alkaloids on humans has led to the development of powerful painkiller medications,
spiritual drugs, and serious addictions by people who are ignorant of the properties of these powerful
chemicals.

Properties:
• Well defined crystalline substances unite with acids to form salts.
• May exist either as free or as salt or as N-oxide ( e.g Strychnine, reserpine, hyoscyamine
)
• Coloured alkaloids are rare e.g Berberine is yellow, salt of sangunarine is copper red.
• Sparingly soluble in water.
• Soluble in organic solvents ( e.g chloroform, ether, alcohol)
• Its salts are sparingly soluble in organic solvents but soluble in water.
• They are water soluble under acidic conditions and lipid soluble under neural and basic
conditions.
• This is especially important for dissolution in protonated form.
• Membrane permeation in deprotonated form.
• Alkaloids have diverse physiological effects: antibacterial, antimitotic, antiinflammatory,
analgesic, local anesthetic, hypnotic, psychotropic, and antitumor activity and many others.
• Most alkaloids contain oxygen in their molecular structure; those compounds are usually
colorless crystals at ambient conditions.
• In plants, alkaloids protect plants from predators and regulate their growth.
CLASSIFICATION
1.Classification based on their origin:
(a)TRUE ALKALOIDS :
• Derived from amino acid
• Contain heterocyclic nitrogen atom in ring
• Basic in nature
• E.g cocaine, morphine etc
(b)PROTO ALKALOIDS:

• Derived from amino acid

• Contain nitrogen atom in aliphatic ring.
• E.g colchicine, ephedrine etc
(c)PSEUDO ALKALOIDS:
• Derived from non-amino acid precursor.
• Contain heterocyclic nitrogen atom
• E.g conine, caffeine etc

2:Classification base on chemical structure

Alkaloids are classify in to two main catagories.

(a)ATYPICAL ALKALOIDS:
• Also called non-heterocyclic alkaloids.
• Contain N-atom in aliphatic chain
(b)TYPICAL ALKALOIDS:
• Also called heterocyclic alkaloids
• Contain N-atom in heterocyclic ring.
3.Chemical Classification of Akaloids
(a) PYRIDINE-PIPERIDINE ALKALOIS:
• Pyridine:It is a six member ring structure, composed of five Carbon atom and nitrogen
(C5H5N).Pyridine compounds are found in nature. For Example:nicotine from tobacco etc
•
• Piperidine:It is a heterocyclic organic compound, derived from pyridine through
hydrogenation.It contain one nitrogen atom in the cycle .The naturally occuring plants belong
to this class is areca nuts, tobacco etc.

(b).Quinoline Alkaloids:
• It contain double carbon ring and one nitrogen atom.The naturally occuring plants belong to
this class is cinchona.
(c).Isoquinoline Alkaloids:
• Isoquinoline is a double carbon ring containing one nitrogen atom. It is more poisonous to
domestic livestock than to human.In human pediatric poisioning is more common.In human
toxicity of this alkaloids is rare because human can ingest toxic alkaloids from the milk of
poisoned animal and manifest symptoms. Plants belong to this class are IPECAC , OPIUM.

(D).Indole Alkaloids:
• They contain one benzene ring attach with nitrogen containing five membered pyrrole ring.
A number of therapeutic drugs belong to this class.Forexample.Rauwolfia,Catharanthus,
Nux-vomica,Ergot.etc

(E).Imidazole Alkaloids:
• They contain imidazole nucleus and are derived from histidine.They act as bases and as
weak acid.Plant belong to this class is pilocarpus(pilocarpine).

(F).Alkaloidal Amines:
• These alkaloid do not possess nitrogen containing heterocyclic ring.The nitrogen atom is
present outside the ring.These are simple amines or their derivatives.They are biosynthesized
by phenyl alanine or tyrosine.
 The plant include this class are Ephedra, colchium etc.

Functions of Alkaloids:

• Alkaloids are poisonous agents of plant against insects and herbivores.

• Alkaloids are regulatory growth factors.
• They reserve substances capable of supplying nitrogen to other elements necessary to the
plant economy.
• These are end products of detoxification reactions representing a metabolic locking up of
compounds otherwise harmful to the plant.
• Some Alkaloids are used in urinary disorders also used as sedative, mydriatic agent,
bronchodilator, local anesthetic, in toothache and to relieve GIT and urinary tract spasms.
• Quinolone Alkaloids are used as Anti-malarial, Anti-pyretic, anti viral analgesic and also to
treat stomachic.
• Imidazole Alkaloids are used to treat Glaucoma.
• Steroidal Alkaloids are used as an anti-inflammatory and as insecticides.
• Purine bases( Tea and coffee) are used as CNS stimulants, flavoring agent , as diuretics,
coffee can inhibit uterine contractions and may increase gastric acid secretions.
 Methods of extraction:
The alkaloids may be extracted by any of the following three well-defined and widely
accepted processes, namely:
• (a)Stas-Otto Process
• (b)Kippenberger's Process
• ( c) General method of extraction:
1. Stas-Otto method:
• The method is based on the distribution of alkaloidal bases between acid or aqueous
solution and immiscible organic solvent.
• Powdered drug is mixed with water and alkali (an alkali is a basic, ionic salt of an
alkali metal or an alkaline earth metal. An alkali can also be defined as a base that
dissolves in water) such as NAOH to make a paste.
• Alkali is added because it is mixed with acids, tannins and other phenolic substances
to make it free of alkaloids.
• The thereafter mixed drug is extracted with chloroform or other organic solvents
using the Soxhlet apparatus.
• This step is carried out because freed alkaloids are dissolved together with other
substances soluble in the solvent.
• Then further re-extract the chloroform layer with dilute sulphuric acid in the
separating funnel and the acid layer is collected. This is because alkaloids are
converted into alkaloidal sulphate which is soluble in water.
• Then in the acid layer water is added so that soluble constituents are passes into the
aqueous solution.
• Then the aqueous layer is mixed with ammonia to make the media alkaline.
• Then evaporate to dryness and the precipitate is collected and dried.
• This step is carried out because ammonia converts alkaloidal sulphate to ammonium
sulphate which is soluble in water.
• The free alkaloids which are insoluble in water, are precipitated.
(i) Plant sample extracted with water or alcohol: The aqueous layer is further extracted
with an organic solvent like chloroform to remove pigments or other impurities
which are soluble in that solvent. Then shake with acid to form a salt of alkaloid in
the aqueous layer. The aqueous layer is then treated with ammonia to get freed
alkaloid which is separated with organic solvents. After evaporation to dryness
residue of alkaloidal extract forms.
(2) Kippenberger’s Process:
• In Kippenberger’s process the powdered and sieved plant substance is first and
foremost digested with solution of tannin (100 g) in glycerol (500 g) at a constant
temperature of 40°C for a duration of 48 hours.
• The resulting mixture is further heated to 50°C so as to help in the complete
coagnlation of proteinous substances
• Cooled to ambient temperature and finally filtered.
• The resulting filtrate is thoroughly shaken with petroleum ether to get rid of faulty
materials (oils, fats and waxes), and the last traces of petroleum ether is removed
from the extract by heating either on a water-bath (electric) or exposure to InfraRed
Lamp.
• The fat-free crude plant extract is subsequently acidified and shaken with chloroform,
successively to remove the bulk of the alkaloids, namely, atropine, codeine,
colchicine, narcotine, nicotine, papaverine, spartenine and thebaine.
• The resulting residual extract may still contain narceine, curarine and morphine.
• However, narceine and morphine may be isolated by passing freshly generated CO2
directly into extract so as to convert the alkali hydroxide into their corresponding
carbonate, which is then ultimately subjected to solvent extraction using a mixture of
alcohol and chloroform.
• Finally, the third alkaloid, curarine, may be extracted by agitation with a mixture of
equal volumes of ether and chloroform.

(c ) General method of extraction:

4.5 Extraction of Alkaloids
Extraction methods vary with the scale and purpose of the operation and with the
raw material. For many research purposes chromatography gives both speedy and
accurate results. However, if an appropriate quantity of alkaloid is required one of
the following general method will usually serve.

Process A: The powdered material is moistened with water and mixed with lime
(Ca(OH)☺ which combines with acids, tannins and other plant substances and set
free the alkaloids (if they exist in plant as salt). Extraction is then carried out with
organic solvents such as ether, chloroform and petroleum spirit. The concentrated
organic liquid is then shaken with aqueous acid and allowed to separate. The
alkaloid salts are now in aqueous liquid while many impurities remained behind in
organic liquid. The scheme of extraction of alkaloids is described in figure 4.1.
Remove the solvent by evaporation and recrystallize it.
Individual members may be separated by fractional extraction or precipitation.
Figure 4.1: Scheme for the extraction of alkaloids from plant sources
48 Pyridine and piperidine alkaloids
48.1 Areca (Areca nut/Betel nut)
Is the dried ripe seed of Areca catechu that belongs to the family Palmae. The fruit
is a nut that contains a single seed with a thin seed coat and a large ruminate
endosperm. The seeds are removed from the fruits boiled in water containing lime
and dried.

Chemical constituents: It contains alkaloids about 0.45%. The alkaloid mixture

composed of arecoline (arecaidine methyl ester), arecaidine (N-methyl guvacine),
guvacine (tetrahydronicitinic acid), govacoline (guvacine methyl ester). The
arecoline is the most abundant and physiologically most active, occurring to the

extent of 0.2%. It also contains tannins (15%), lipids, volatile oil and gums.
Uses:
It is used as anthelmintic in veterinary practice.
It is employed as vermicide and taenifuge in mammals.
4.8.2 Lobelia (Indian Tobacco)
It consists of the dried leaves and tops of Lobelia inflata that belongs to the family
Lobeliaceae.
Chemical constituents: It contains fourteen alkaloids of which lobeline is the
major and the most important one. It also contains pungent volatile oil, resin, lipids
and gums.
Uses:

-Lobeline produces similar but weaker pharmacological effects to those of nicotine on the
peripheral circulation, neuromuscular junctions and CNS.
-It is incorporated in tablets or lozenges that are intended to aid in giving up the habit. Iii. 3-An
injection of lobeline hydrochloride is used in the resuscitation of new born infants.

4.9 Tropane alkaloids

Tropane is a bicyclic compound formed by the condensation of a pyrrolidine
precursor with acetate-derived carbon atoms. Both pyrrolidine and piperidine ring
systems can be discerned of the molecule.

4.9.1 Belladonna (Belladonna leaf/Belladonna herb/Deadly nightshade leaf)

It consists of the dried leaf and flowering or fruiting tops of Atropa belladonna that
belong to family Solanaceae. Belladonna leaf yield not less than 0.35% of
alkaloids.
Atropa is from “atropos”, meaning inflexible, Belladonna is from the Italian “bella”
Meaning beautiful and “donna” meaning lady. The juice of the berries when placed
in the eyes Cause the dilation of the pupils, thus giving striking appearance.

Chemical Constituents: It yields alkaloids in concentration ranging up to more

than 1%. About three-fourth of the isolated alkaloid mixture is (-)-hyoscyamine, the
remainder is atropine. Atropine exists only in traces in fresh plant material. It is
formed by racemization during extraction process. Small but varying amounts of
other bases are found in roots but not in leaf These include apo-atropine,
belladonine, cuscohygrine and scopolamine. The average yield of alkaloids in
various parts of plant is as under:- roots (0.6%), stems (0.05%), leaves (0.4%), u
beries (0.19%), ripe beries (0.21%), seeds (0.33%).
 Uses:
• iBelladonna acts as parasympathetic depressant which accounts for its use as
spasmolytic agent
• The drug is used as adjunctive therapy in the treatment of peptic ulcer, functional
digestive disorders, including spastic, mucous and ulcerative colitis, diarrhea,
diverticulitis and Pancreatitis.
• İt possesses anticholinergic properties and is used to control excess motor activity of
the GIT and spasm of the urinary tract.

49.2 Hyoscyamus (Henbane, Indian henbane)

Hyoscyamus is the dried leaf, with or without stem and flowering or fruiting tops of
Hyoscyamus niger that belong to the family Solanaceae. It contains not less than
0.04% of the alkaloids.

Chemical Constituents: It contains alkaloids in a concentration ranging from 0.05-

0.15 About three-fourth of the isolated alkaloid mixture is (-)-hyoscyamine, the
remainder is hyoscine.

Egyptian henbane
Egyptian henbane is the dried leaves and flowering tops of Hyoscyamus muticus
(Solanaceae). It yields about 1.5% of total alkaloids. Major portion of alkaloids
mixture is hyoscyamine.

493 Stramonium (Jimson weed)

It consists of the dried leaf and flowering or fruiting tops with branches of Datura
stramonium or its variety tatula that belong to the family Solanaceae. It yields not
less than 0.25% of the alkaloids

Chemical Constituents: The drug contains hyoscyamine and hyoscine

(scopolamine), the former more abundantly. It serves as source of atropine.
Uses:
• Stramonium is an anticholinergic and has an action like that of belladonna,
• Powdered stramonium is an ingredient in preparations that are intended to Burn, the
resultant vapors are inhaled for the relief of asthma.
Stramonium seeds: It contains about 0.4% of alkaloids principally hyoscyamine
with small Amount of hyoscine and traces of atropine.

4.9.4 Uses of solanaceous alkaloids

Solanaceous alkaloids include hyoscyamine, atropine (racemic hyoscyamine),
hyoscine (scopolamine), apo-atropine (anhydride of atropine) and belladonine.
Atropine and scopolamine are competitive with acetylcholine at postganglionic
synapse (muscarinic sites) of the parasympathetic nervous system. Clinically useful
effects obtained from blocking muscarinic activity of acetylcholine include:

• An antispasmodic effect used principally to relieve spasm of bowel in the treatment of spastic
colitis, gastroenteritis and peptic ulcer.
• An antisecretary effect is used to reduce respiratory secretions in anesthesia
(antisialgogue), gastric secretion in peptic ulcer therapy, nasal and sinus secretions in
Common cold and in allergic manifestations.

• A mydriatic and cycloplegic effect is used to prevent adhesions between the iris and lens Of eye
in cases of iritis.
• Atropine is an antidote in cases of poisoning caused by choline esterase inhibitors such as
Physostigmine and organophosphate insecticides.
• Scopolamine has a depressant activity on CNS and is used to treat motion sickness,
as pre- anesthetic sedation, for obstetric amnesia in conjunction with analgesics and
to calm delirium.

4.10 Quinoline alkaloids

4.10.1 Cinchona (Cinchona bark/Peruvian bark).

Cinchona is the dried bark of stem or of the root of Cinchona succirubra or its
hybrids known in commerce as red cinchona or Cinchona ledgeriana, C. Calisaya
or hybrids of these with other species of Cinchona known in commerce as calisaya
bark or yellow cinchona. It belongs to the Family Rubiaceae.

Chemical constituents:

• Cinchona contains about 25 closely related quinoline alkaloids, the most important of
which are quinine, quinidine, cinquinine and cinquinidine. The average yield alkaloids
is 6-7%. The one-half to two-third (1/2-2/3) of total alkaloid is of quinine in yellow
burk. In red barks cinquinine exists in greater proportion. Specimen pieces yielded as
high as 18° of total alkaloids.
• Another constituent of cinchona is cinchotannic acid (2-4%) which decomposes into
the nearly insoluble cinchona red, occurring in red barks to the extent of 10.
Cincotannic acid is a phlobatannin.
• Other constituents are a-quinovin (2-4%) which is a glycoside yielding on hydrolysis
Quinovaic acid and quinovose (isohydrose).
• It also contains quinic acid up to the extent of 5-8%.
 Red color of Cinchona bark caused by an oxidase that causes fruits to darken when
cut. If fresh bark is heated in boiling water for 30 minutes and then dried it does not
become red.

Quinine Quinidine Quinic Acid

Uses:

• Cinchona and its alkaloids have been used in the treatment of malaria fever for many
years. Quinine continues to be used for malaria in many parts of the World.
• The galenicals of cinchona are used as bitter tonics and stomachics.
• On account of astringent action, a decoction and acid infusion are sometimes used as
gargles.
• Quinidine is employed for the treatment of cardiac arrhythmias such as premature atrial,
AV junctional and ventriculal contractions, atrial flutter and atrial fibrillation.

An overdose of cinchona products results in temporary loss of hearing and impaired

sight. Ringing in the ear is a symptom of toxicity. When these symptoms are produced
as a result of continuous use of cinchona and quinine, the condition has been called
cinchotism.

4.11 Isoquinoline alkaloids

4.11.1 Opium (Gum opium)
Opium is the air dried milky excudate obtained by incising the unripe capsule of
Papaver somniferum that belongs to the family Papaveraceae. The term opium is
from the Greek "opion” meaning poppy juice. "Papaver" is a Latin name for the
poppy,"somniferum" is a latin and means to produce sleep.

Chemical constituents:

More than 30 alkaloids have been obtained from the opium and its extracts and some
of which are alteration products of the alkaloids occurring naturally. The most
important of these are:

• morphine (4-21%)
• codeine (0.8-2.5%)
• noscapine (4-8%)
• papaverine (0.5-4%)
• thebain (0.5-2%).

Other alkaloids include: narceine, protopine, laudanine, codamine, cryptopine,

lanthopine and meconidine.
Opium also contains 3-5% of meconic acid which exists free or in combination with
morphine and codeine.

The total ash yield of opium is 4-8% with about 0-0.55% of acid insoluble ash.

Morphine R=OH ; Codeine R=OCH3 Noscapine Papaverine

Uses:

The alkaloids present in opium decrease in narcotic properties in the order of morphine, codeine
and noscapine. Opium and morphine are widely used to relieve pain (analgesic) and are
particularly valuable as hypnotics. They act mainly on the sensory nerve cells of the cerebrum.

• Codeine is milder sedative than morphine and is useful for alloying cough.
• Noscapine and codeine have antitussive properties.
• It checks excessive peristalsis therefore used in the treatment of diarrhoea.
• The habitual use of opium may produce constipation.
• Papaverine is used as skeletal muscle relaxant.

4.11.2 Ipecac
It consists of the dried rhizomes and roots of Cephaelis ipecacuanha (Brazilian or
Rio Ipecac) and of Cephaelis acuminata (Nicaragua or Panama Ipecac) that belongs
to the family Rubiaceae. The drug yields not less than 2% of ether soluble alkaloids
of ipecac.

Chemical constituents:

Ipecac contains five alkaloids (2-2.5%). The three principal alkaloids which are
present chiefly in the bark include:
• Emetine
• cephaeline
• psychotrine.
• It also contains starch about 40%.
• Rio ipecac contains about two-third of emetine.
• Panama ipecac contains about two third of cephaeline.
 Psychotrine

Uses:

• It is used in the form of syrup for the treatment of drug overdose and in certain poisoning.
It produces emesis through a local irritant effect on the gastrointestinal mucosa and a
central medullary effect by stimulation of the chemoreceptor trigger zone.
• It also possesses expectorant properties and is used to relieve productive cough.
• Emetine also possesses anti-amebic activity.

4.11.3 Hydrastis (Goldenseal): It consists of the dried rhizomes and roots of

Hydrastis canadensis (Ranunculaceae). It contains alkaloids i.e. hydrastine, canadine
and berberine. It is used as an astringent and for the inflammation of mucous
membranes.

4.11.4 Sanguinaria (Blood root): It consists of the dried rhizomes of

Sanguinaria canadensis (Papaveraceae). Major alkaloid is sanguinarine which is
odorless and form reddish salt with nitric acid. It is used as an expectorant and an
emetic.

4.11.5 Curare (South American arrow poison): It is the crude dried extract
from the bark and stem of Strychnos castelnaei, S. toxifera, S. crevauxii and
Chondodemdron tomentosum.

It contains alkaloid "tubocurarine". It is skeletal muscle relaxant to secure muscle

relaxation in surgical procedures without deep anesthesia. It is also used to control
convulsions of strychnine poisoning and of tetanus.
 Berberine

Hydrastine

Sanguinarine

Tubocurarine

4.12 Indole alkaloids

4.12.1 Rauwolfia
Rauwolfia is the dried roots of Rauvolfia serpentina that belongs to the family
Apocynaceae. It contains not less than 0.15% of reserpine-rescinnamine group of
alkaloids calculated as reserpine.

Chemical constituents:

Rauwolfia contains at least 30 alkaloids (0.7-2.5%). Other substances include:

phytosterol, fatty acids, unsaturated alcohols and sugars.

In 1931 Siddiqui and Siddiqui isolated:

• Ajmaline
• Ajmalinine
• Ajmalicine
• Serpentine
• Serpentinine

FİG: RESERPINE
But the chief therapeutically important alkaloids isolated from the drug are:
• reserpine (1952)
• rescinnamine (1954)
• deserpidine.

Uses:

• Rauwolfia preparations and reserpine are used in the management of essential

hypertension (antihypertensive) and in certain neuropsychiatric disorders (tranquilizer).
• Ajmaline, which has pharmacological properties similar to that of quinidine, is marketed
in Japan for the treatment of cardiac arrhythemias.
• Ajmalicine (isolated from rauwolfia and catharanthus species) marketed for the
treatment of circulatory diseases.

Sources of Reserpine: Reserpine has been obtained in commercial quantities from

four different species of Rauwolfia i.e. Rauwolfia serpentina, R. micrantha, R.
tetraphylla and R. vomitoria.

4.12.2 Catharanthus
Catharanthus is the dried whole plant of Catharanthus roseus that belongs to the
family Apocynaceae. The plant was formerly designated as Vinca rosea.

Chemical constituents:

More than 70 alkaloids have been isolated from catharanthus. They are :indole and
dihydroindole derivatives.

The important dimeric alkaloids are:

• Vinblastine
• Vincristine
• Vinrosidine
• Vinleurosine

Vinblastine:
R=CH₂
Vincristine:
R=CHO
Monomeric alkaloids include: ajmalicine, serpentine
and tetrahydro-alstonine.

The antineoplastic activity lies with the dimeric alkaloids.

Uses:

• Vinblastine is recommended for generalized Hodgkin's disease, lymphocytic

lymphoma, histocytic lymphoma, mycosis fungoides, advanced testicular sarcoma,
kaposi's sarcoma, choriocarcinoma and breast cancer unresponsive to other therapies.
• Vincristine is recommended for the treatment of acute leukemia and in combination
therapy for hodgkin's disease, lymphosarcoma, reticulum cell sarcoma,
rhabdomyosarcoma, neuroblastoma and Wilm's tumor.

4.12.3 Nux vomica

Nux vomica is the dried ripe seeds of Strychnos nux-vomica that belongs to the family
Loganiaceae.

Chemical constituents:

It contains 1.5-5% of alkaloids consisting chiefly of strychnine amd brucine. The

strychnine is 1/3 to 1/2 of the total alkaloids.

The minor related alkaloids are:

• Coluberine
• B-colubrine
• Icajine
• 3-methoxyicajine
• Protostrychnine
• Vomicine
• Novacine
• Oxystrychnine
• Pseudostrychnine
• Isostrychnine.
• Seeds also contain chlorogenic acid, glycoside loganin and about 3% of fixed
oil.
 Strychnine: R=H
Brucine:
R=OCH₂

Uses:

• The effects of whole drug closely resemble to that of strychnine. The alkaloid was
formerly used as a circulatory stimulant in such cases as surgical shocks. But its use is
now more limited to that of respiratory stimulant in certain cases of alcohol poisoning.
• Strychnine improves the appetite and digestion (bitter).
• Nux vomica increases the tone of intestine.
• It is given in atonic dyspepsia.

4.12.4 Physostigma (Calabar beans)

Physostigma is the dried ripe seeds of Physostrigma venenosum that belongs to the
family Leguminosae. It yields not less than 0.15% of the alkaloids.

Chemical constituents:

It contains several alkaloids that include:

• Physostigmine (eserine)
• Eseramine
• Geneserine
• Physovenine
• Isophysostigmine
• N-8-norphysostigmine Physostigmine

Uses:

It is a reversible inhibitor of the choline esterases (cholinergic) and thus enhances the
effect of endogenous acetylcholine. In the eyes increase in cholinergic activity leads
to miosis, contraction of ciliary muscles and a decrease in intraocular pressure caused
by an increased outflow of the aqueous humor. Physostigmine is employed in
ophthalmology to treat glaucoma.

Ergot:
Ergot is the dried sclerotium of Claviceps purpurea (Clavicipitaceae) developed on
the plants of rye( Secale cereal) that belongs to the family Gramineae. Ergot was
required to yield not less than 0.15% of the ergot alkaloids calculated as ergotoxine
and water-soluble alkaloids equivalent to less than 0.01®% of ergonovine.
Sources of ergot alkaloids
Claviceps purpurea on rye (parasitic): both peptide and non peptidal alkaloids
claviveps paspali (saprophytic culture): nonpeptidal alkaloids only
Chemical constituents:
The ergot contains a large number of alkaloids which are chemical derivatives of
lysergic acid and its optical isomer isolysergic acid. The lysergic acid derivatives
are found to be medicinally important. The therapeutically most active alkaloids are
ergonovine and ergotamine and a mixture of ergocristine, ergokryptine and
ergocormine that has been marketed under the name of ergotoxine. Other
constituents include fixed oil, sterols, histamine, tyramine, and several pigments.

USES:
• Ergot is oxytocic, vasoconstrictor, and abortifacient.
• It is used to assist delivery and to reduce post-partum hemorrhage.
• It is used to treat migraines.
• Lysergic acid diethyl amide is a potent specific psychotomimetic.
ERGOT ALKALOIDS:
It includes constituents of ergot and the semisynthetic derivatives such as
ergonovine and ergotamine.
ergotoxine, methyl ergonovine, methylsergide, dihydro ergotamine, dihydro
ergotoxine
ergonovine (Ergometrine): Ergonovine is oxytocic and is used to assist
delivery. It stimulates the tone of uterine muscles and prevents post-partum
hemorrhage. (effects by partial agonist or antagonist at a-adrenergic, dopaminergic
and serotonin receptors)
Methyl ergonovine: it is semisynthetic homolog of ergonovine prepared from
lysergic acid and 2-aminobutanol. It is an oxytocic to be slightly more active and
longer action than ergonovine. It is available in the market under the name
Methergin.
Methsergide meleate: It is salt of methylergonovine that has an additional methyl
group attached to the nitrogen at position 1 of the lysergic acid nucleus. It is
serotonin antagonist employed in prophylaxis of vascular headache.
Ergolamine tartrate: It possesses oxytocic properties, but it is not employed for
that effect. It is categorized as a specific analgesic in the treatment of migraine.
Ergotamine reduces extracranial blood flow and decreases the amplitude of
pulsation in the cranial arteries that have been associated with migraine. It may
inhibit receptor uptake of non-epinephrine at sympathetic nerve endings, increasing
the vasoconstrictor action. Ergotamine is used with caffeine for the treatment of
migraine headache, Both act as cerebral vasoconstrictor. Caffeine is believed to
enhance the action of ergotamine (Cafergot). (Dose: 2 mg after every 30 minutes if
necessary up to 6 mg per 24hrs and do not exceed 10 mg/ week.)
Dihydro-ergotamine mesylate: It is semisynthetic alkaloid prepared from
ergotamine by hydrogenation of the A- double bond in the lysergic acid nucleus. It
is used in the treatment of migraine because it is more effective and better tolerated
than the parent alkaloid. (Dose is parenteral 1 mg repeated at 1 hour interval up to 3
mg).
Ergotoxine: It was formerly employed as reference standard in the form of
ergotoxine ethane sulfonate which was discontinued because it was a variable
mixture of three closely related alkaloids namely ergocristine, ergokryptine and
ergocornine. A mixture of equal parts of these ponent alkaloids are hydrogenated at
A- double bond in the lysergic acid nucleus to yield an alexture of dihydro-
ergocristine, dihydro-ergokryptine and dihydro-ergocomine. The methane
sulfonates of this mixture, known as ergoloid mesylates (Hydergine), are marketed
for the treatment of selected symptoms in elderly patients. It produces
vasoconstriction, increased cerebral blood flow, lowering of systemic blood
pressure and bradycardia.
Lysergic acid Diethylamide: It does not occur in nature but is prepared by semi
synthesis. It has two-fold actions i.e., producing a predominant central sympathetic
stimulation that parallel, a slight depression and it is the most active and most
specific psychotomimetic agent known. It valuable in experimental psychiatry.
4.13 Imidazole alkaloids
4.13.1 Pilocorpus
It consists of the dried leaflets of Pilocarpus jaborandi (Jaborandi), or of P.
microphyllus (Maranham jaborandi), or of P. pinnatifolius (Paraguay jaborandi), or
of P. trackylophus (Cerca jaborandi) that belong to the family Rutaceae. The plants
are shrubs and indigenous to Brazil All of the commercial kinds of pilocarpus when
freshly dried, yield 0.5-1% of alkaloid pilocarpine Isopilocarpine, pilocarpidine and
pilosine are present in some of the species. Even under ideal storage conditions, the
leaves lose at least half of their alkaloid content in one year through deterioration.
Leaves that are two years old are practically worthless.

pilocarpine
Pilocarpine is the lactone of pilocarpic acid (an acid with glyoxaline nucleus). It is
an oily syrupy liquid, though its salt crystallizes easily. It may be obtained by
treating the powdered leaves with sodium carbonate, extracting with benzene. Then
shaking the benzene extract with diluted hydrochloric acid or dil. nitric acid. The
Aqueous solution is then made alkaline and shaken with chloroform. The
chloroform extract is then shaken with dil. acid and the alkaloid salt is allowed to
crystallize.
Uses:
Pilocarpine directly stimulates the muscarinic receptor (cholinergic) in eye causing
constriction of the pupil and contraction of ciliary muscles thus used in the
treatment of glaucoma.
4.14 Purine Bases
4.14.1 Tea (Thea)
It consists of the prepared leaves and leaf hauls of Camellia sinesis (types of tea
available in the market.
Green tea: It is prepared in China and Japan by rapidly drying the freshly picked
leaves in
pans over a mild artificial heat. Leaves are often rolled in the palms of hand as they
dry.

Black tea: It is prepared in Sri Lanka and India by heaping the fresh leaves until
fermentation has begun. They are then rapidly dried artificially by heat.
Chemical constituents: Tea contains caffeine (1-4%) and small amounts of
theophylline theobromine, adenine, and xanthine. It also contains gallotannic acid
(about 15% volatile yellow oil (0.75%) that is solid at ordinary temperature and has
strong aromatic odor and taste.
4.14.2 Coffee beans (Coffee seeds)
It consists of the dried ripe seeds of Coffea arabica, or of C. liberica. It belongs to
the family Rubiaceae.
Chemical constituents: Coffee seeds contain caffeine (1-2%), trigonelline (0.25
5%) tannins 3-5%. Fatty oil (palmitin, olein) 10-13%), proteins (10-13%).
When the coffee is roasted, the seeds swell, change in color to dark brown and
develop a characteristic odor and flavor. The aroma is caused by an oil "caffeol"
consisting of about 50% furfurol with traces of valerionic acid, phenol, and
pyridine. At the same time caffeine is freed from its combination with chlorogenic
acid with which it exists in the unroasted seeds. The caffeine may be partially
sublimed during this roasting process. Much of the caffeine in commence is
collected in the condensers attached to the coffee roasters.

Uses:
Methylxanthines (caffeine, theophylline, theobromine) competitively inhibit
phosphodiesterase which Methylxanthine (caffeine, theophylline, theobromine)
competitively inhibits phosphodiesterase Which results in an increase of cyclic
AMP with a subsequent release of endogenous epinephrine This results in direct
relaxation of the smooth muscles of the bronchi, pulmonary blood. stimulation of
central nervous system, an introduction of diuresis, an increase in gastric acid
secretion, an inhibition of uterine contraction, and a weak positive chronotropic and
ionotropic effects on heart
. Caffeine and its related compounds are CNS stimulants. Theophylline acts as
smooth muscle relaxant therefore used for symptomatic relief of bronchial asthma
and for the treatment of reversible bronchospasm associated with chronic bronchitis
and emphysema. It also possesses diuretic properties. Theobromine on the other
hand, has prominent diuretic and smooth muscle relaxant properties with little CNS
stimulation activity and hence preferred over caffeine for the treatment of cardiac
edema and angina pectoris.
4.14.3 Kola: It is the dried cotyledons of Cola nitida and other species of Cola that
belongs to the family Sterculiaceae. It contains caffeine (up to 3.5%), theobromine
(less than 1%).
4.14.4 Maté: It consists of the leaves of Ilex paraguariensis that belong to the
family Aquifoliaceae. It contains caffeine (up to 2%) and tannins.
4.15 Steroidal Alkaloids
4.15.1 Veratrum viride
It consists of dried rhizome and roots of Veratrum viride (Liliaceae). It contains
large number.
alkaloids that can be divided into three groups.
i. Alkamines (steroidal bases): Germine, jervine, rubijervine and veratramine.
ii. glycosides of alkamines: Pseudojervine, veratrosine.
iii. Esters of alkamines: Cevadine. germidine, protoveratrine, neoprotoveratrine,
veratridine. germitrine,
neo-germitrine
The ester alkaloids germidine and germitrine are probably the most important
therapeutically.
Uses:
It possesses hypotensive, cardiac depressant and sedative properties and is used as
antihypertensive.
4.15.2 White hellebore (European hellebore):
It consists of dried rhizome of Veratrum alba.It contains steroidal bases, glyco-
alkaloids and alkaloid esters similar to that of veratrum viridae
Among them the alkaloid esters namely protoveratrine A and protoveratrine B are
the most active constituents.
4.16 Alkaloidal Amines
4.16.1 Ephedra (Mahuang)
It consists of the dried entire or over ground portion of Ephedra sinica that belongs
to the family Genetaceae. Chinese character "Ma" means astringent and "huang"
means yellow.
Chemical constituents: It contains 0.5-2% of alkaloids that includes (-)-ephedrine.
Pseudo ephedrine, 1-methylephedrine, nor-ephedrine.
Uses:
i. It is a potent sympathomimetic that stimulates a- and B-adrenergic receptors.
ii. It excites sympathetic nervous system, causes vasoconstriction, cardiac
stimulation. produces effects similar to those of epinephrine.
iii. It is classed as bronchodilator and is used in asthma, rhinitis, and hay fever.
Sources of ephedrine: It includes Ephedra sinica, Ephedra equisetina (chief
source) and Ephedra.
Distachya

4.16.2 Colchicum Corm and Colchicum Seeds

Colchicum corm and colchicum seeds are the dried ripe seeds and corms of
Colchicum automnale (Liliaceae). Indian drug is obtained from Colchicum luteum.
Chemical constituents: It contains alkaloid colchicine (0.08% in seeds and 0.6% in
corms). demecolcine.

Colchine demecolcine
Uses:
• It is gout depressant and is used to cure gout and rheumatism.
• It is used in myeloid leukemia.
• It is used to produce polyploidy in biological experiments.
The exact mechanism of action in the treatment of gout is not known. It does inhibit
leukocytes migration and reduces lactic acid production by leukocytes which
results in a decreased deposition of uric acid. In addition, there is a reduction in
phagocytosis which decreases the inflammatory response.
4.16.3 Khat: It consists of the fresh leaves of Catha edulis that belongs to the
family Celastreacea. Leaves are chewed habitually to alleviate the sensation of
hunger and fatigue by African and Arabian people.
It contains (-)-cathinone. The pharmacological properties of cathinone are similar to
amphetamine i.e., potency, mode of action (induction of catecholamine from
storage site).

cathinone

xol (Paclitaxel)
It is a pseudoalkaloid obtained from the bark of Taxus brevifolia (pacific yew) that
belongs to family Taxicaceae. Bark of the mature tree (100 years of age) contains
0.01-0.02% of taxol.
Bark of three mature trees yields 1 gm of taxol whereas at least 2 gm of taxol is
required for complete course of treatment.
Bark also contains other diterpene taxanes such as 10-deacetyl taxol, Baccatin-III
(0.2%) and
deacetylbaccatin-III.
TAXOL

Taxol is used in ovarian cancer, breast cancer, non-small cell lung cancer. It also has
potential value against other can