ALKALOIDS

OBJECTIVES

To know what are the characteristics of

alkaloids

To know the different sources of alkaloids

To determine the importance of alkaloids and

to identify their applications in pharmacy

To know the different test in determining the

presence of alkaloids

WHAT ARE ALKALOIDS?

These are commonly applied to basic

nitrogenous compounds of plant origin

that are physiologically active.

Organic nitrogenous compounds with a

limited distribution in native nature.

STRUCTURE OF ALKALOIDS

CHARACTERISTICS:

They are bitter in taste.

Derived from amino acids

Alkaloids form double salts with

compounds of mercury, gold, platinum

and other heavy metals. These salts are

obtained as precipitate which are

microcrystallographic.

Most but not all alkaloids possess

basic properties owing to the

presence of amino nitrogen.

Structurally complex end products of

energy- requiring reaction

sequences.

Alkaloids usually contain one nitrogen

atom but some may contain 5 nitrogen

atoms such as ergotamine. The

nitrogen may exist as a primary amine

(RNH2), secondary amine (R2NH),

tertiary amine (RN), or as quaternary.

PROPERTIES OF ALKALOIDS

Insoluble or sparingly soluble in water,

but the salts formed on reaction with

acids are usually freely soluble.

Most are crystalline solids although a

few are amorphous.

Free alkaloids are usually soluble in

ether, chloroform, or other relatively

non-polar immiscible solvents.

Some alkaloids are liquid because of

lacking of oxygen in their molecules.

(e.g coniine, nicotine, spartenine)

The degree of basicity varies greatly,

depending on the structure of the

molecule and the presence and

location of other functional groups.

Have high melting points

SOURCES AND OCCURRENCE OF ALKALOIDS

Alkaloids can occur in plant kingdoms;

among the angiosperms, the

Leguminosae, Papaveraceae, Ranunculaceae,

Rubiaceae, Solanaceae, and Berberidaceae

are outstanding alkaloid-yielding

plants.

The Labiatae and Rosaceae are almost

free of alkaloids; the gymnosperms only

rarely contain them (Taxaceae).

Specific alkaloids are confined to specific

plant families such as hyoscyamine in

Solanaceae, colchicine in Liliaceae

Although it has been claimed that the

monocotyledons do not generally

produce alkaloids, investigations indicate

that the Amaryllidaceae and Liliaceae are

two of the most promising families (of a

list 11) in which to search for alkaloid-

yielding plants.

Occur in fungi (e.g ergot from Claviceps

purpurea)

Occur in various parts of the plant; in

seeds (physostigma, areca),

underground stems (sanguinaria), roots

(belladonna root), rhizomes and roots

(ipecac, hydrastis), barks (cinchona).

USES OF ALKALOIDS IN PLANTS:

Poisonous agents which protect plants

against insects and herbivores

End products of detoxification reactions

representing a metabolic locking-up of

compounds otherwise harmful to the

plants.

For regulatory growth factors

Reserve substance capable of

supplying nitrogen or other elements

necessary to the plant’s economy

PHARMACOLOGIC ACTION OF ALKALOIDS:

Analgesic (morphine, codeine) Narcotics (strychnine, brucine which

are central stimulant) Mydriatics (atropine) Miotics (physostigmine, pilocarpine) Ephedrine (rises in blood pressure) Reserpine (produce fall in excessive

hypertension)

BIOSYNTHESIS OF ALKALOIDS

The biosynthesis of many alkaloidal

structures can be rationalized through

simple chemical reactions that involve

amino acids.

The amino acids that are most often

serve as alkaloidal precursors are: phenylalanine, tyrosine, tryptophan, histidine,

anthranilic acid, lysine and ornithine.

Some of the general reactions that are of

particular importance include: decarboxylation

(removal of carboxyl group or carbon dioxide)

and transamination (transfer of an amino group

from one molecule to another without the

formation of ammonia) of the amino acids to

yield a corresponding amine or aldehyde.

These can react to form a Schiff base which, in

turn can react with carbanion in a Mannich-type

condensation.

TEST FOR ALKALOIDS

Wagner’s Test

(+) Reddish brown precipitateReagent used: Wagner’s Reagent

[Solution of iodine in potassium iodide]

Mayer’s Test

(+) Cream color precipitatesReagent used: Mayer’s Reagent

[Potassium mercuric iodide solution]

Dragendorff’s test

(+) Orange precipitate

Reagent used: Dragendorff’s reagent

[Potassium bismuth iodide solution]

Hager's test

(+) Yellow color precipitate

Reagent used: Hager's reagent

[saturated solution of Picric acid]

Tannic acid test

(+)buff color precipitate

Reagent used: 10% Tannic acid solution

Valser’s Test

(+) white precipitate

Reagent used: Valser’s reagent

(Mercuric Iodide TS

NAMING FOR ALKALOIDS

From the generic name or the genus of the plant

yielding them (e.g hydrastine, atropine)

The specific name or species of the plant yielding

alkaloids ( e.g cocaine, belladonnine)

Common name of the drug yielding them (e.g

ergotamine)

From their physiologic activity (e.g

emetine, morphine)

From the discoverer (e.g pelletierine)

~ All names of alkaloids should end in “-

ine”.

~ A prefix or suffix is added to the name of

a principal alkaloid from the same source.

(quinine, quinidine, hydroquinine)

CLASSIFICATION OF ALKALOIDS

Pyridine- Piperidine Combined Tropane Quinoline Isoquinoline Indole Imidazole Steroid Alkaloidal amine Purine

PYRIDINE- PIPERIDINE COMBINED

Also referred to as Pyrrolizidine

alkaloids

Upon reduction, the tertiary base,

pyridine, is converted into the

secondary base, piperidine.

3 Subgroups

Derivatives of piperidine

Derivatives of nicotinic acid

Derivatives of both pyridine and

pyrrolidine

Important alkaloidal drugs and alkaloids that are classified in this group are:

Areca Arecoline Hydrobromide Lobelia Lobeline Nicotine

NICOTINE

A primarily product of

root metabolism, but

the formation of small

amounts, as well as

subsequent reactions

such as demethylation

of nicotine, can occur

in leaves of plants.

It is a pyridine alkaloid obtained from

the dried leaves of the tobacco plant

Nicotiana tabacum Linné (Fam.

Solanaceae)

Nicotiana – was named after Jean

Nicot who introduced tobacco in

Europe

Tabacum – refers to the Indian name

for the pipe or tube used in smoking it

It is colorless to pale yellow, very

hygroscopic, oily, volatile liquid with

unpleasant, pungent odor and a sharp,

burning, persistent taste.

USES:

It is bound to an ion exchange resin in a

chewing gum base as a temporary aid to

the cigarette smoker seeking to give up

smoking.

Chronic use of nicotine may result in

psychological and physical dependence.

ARECA

Areca nut or Betel Nut

A dried, ripe seed of

Areca catechu

(Fam. Palmae)

Areca- a Spanish

and Portuguese

term for betel nut

Catechu- East Indian name for an

astringent extract or juice

Areca mixed with lime, the leaves of Piper

bette Linné and occasionally gambir is

known as “PUNSUPARI”. This mixture is

used as a stimulant masticatory.

Consists of 0.45% alkaloids, 15% tannins,

lipids, volatile oils and gum.

Uses:

Pharmaceutic purposes

Anthelmintic or vermicide in veterinary

practice

Taenifuge

Constituents: These are reduced

pyridine derivatives.

Arecoline (arecaidine methyl ester) <most

abundant and physiologically active>

Arecaidine (N-methyl guvacine)

Guvacine (Tetrahydronicotinic acid)

Guvacoline (Guvacine methyl ester)

LOBELIA

Indian tobacco

Consists of dried leaves

and tops of Lobelia

inflata Linné (Fam.

Lobeliaceae)

Lobelia – named in

honour of a Flemish

botanist Matthias de L’

Obel

Inflata – refers to a hollow and distended fruit

Substitute for tobacco

Uses:

• Similar but weaker pharmacological effects

in nicotine on the peripheral circulation,

neuromuscular junctions, and CNS.

• Anti-smoking preparations

Lobeline sulfate incorporated in tablets or

lozenges are smoking deterrents.

Lobeline had placebo effect on decreasing the

physical craving for cigarettes.

Traditionally used by the Native Americans for

asthma Chronic bronchitis

Injection of lobeline hydrochloride is used in

the resuscitation of newborn infants

Constituents:

Contains 14 alkaloids which

LOBELINE is the major and most important.

It has a pungent, volatile oil, resin, lipids,

and gum.

Lobeline, (-) – lobeline or alpha lobeline

This occurs as colorless crystals which are

slightly soluble in water but readily soluble in

hot alcohol.

TROPANE ALKALOIDS

A dicyclic compound formed by the condensation

of a pyrrolidine precursor (ornithine) with three

acetate-derived carbon atoms. Both pyrrolidine

and piperidine ring system can be discerned in

the molecule.

The 3-hydroxy derivative of tropane is known as

tropine. Its esterification with (-)- tropic acid

yields hyoscamine (tropine, tropate), which may

be racemized to form atropine.

Important alkaloidal drugs and alkaloids that are classified in this group are:

Belladonna leaf Hyoscyamus Stramonium Atropine Hyoscyamine Scopolamine Coca Cocaine

BELLADONNA

Belladonna leaf,

Belladonna herb or deadly

nightshade leaf

Consists of dried leaf and

flowering or fruiting top of

Atropa belladonna Linné or

of its variety acuminata

Royle ex Lindley (Fam.

Solanaceae)

Atropa – is from Atropos meaning inflexible

Belladonna – from Italian word

“bella” meaning beautiful and “donna”

meaning lady

Uses:

It acts as an antimuscarinic agent

which accounts for its use as a

spasmolytic drug.

Treating diarrhea, diverticulitis ,

pancreatitis

Used as a adjunctive therapy in the treatment

of peptic ulcer; functional digestive disorders

It possesses anticholinergic properties and is

used to control excess motor activity of the GI

tract and spasm of the urinary tract.

It is commonly administered in the tincture

(3mg alkaloids/ 100ml) or the extract (1.25 g

alkaloids/100g)

Constituents:

(-)- hyoscyamine remainder atropine Apoatropine Belladonnine Cuscohygrine Scopolamine

SOLANACEOUS ALKALOIDS

The principal alkaloids of this group are:

(-) hyoscyamine

atropine [(±) – hyoscyamine]

scopolamine (also known as hyoscine)

These are tropine derivatives and esters and may

be prepared synthetically but are usually

obtained by extraction from plants of the

Solanaceae such as:

Atropa belladonna

Datura stramonium

Hyoscyamus niger

Hyoscyamus muticus (also known as Henbane)

Dubosia plants

Atropine

An antidote in case of poisoning

caused by cholinesterase inhibitors.

It is a CNS stimulant.

Scopolamine

It has a depressant activity on the

CNS.

It is used to treat motion sickness.

It is employed for preanesthetic

sedation and for obstetric amnesia in

conjunction with analgesics and to

calm delirium.

Toxicity symptoms occur in using atropine, scopolamine and belladonna tincture include:

Skin rash Skin flushing Mouth dryness Difficulty in urination Eye pain Blurred vision Light sensitivity

Hyoscyamine

a tropine ester of (-)-tropic acid

Hyoscyamine sulfate

extremely poisonous

It occurs as white, odourless crystals or as

crystalline powder.

It is a deliquescent and is affected of light.

It is an anticholinergic and used as an

aid in the control of gastric secretion,

visual spasm, hypermotility in spastic

colitis, pylorospasm and abdominal

cramps.

In Parkinsonism, it is used to reduce

rigidity and tremors and to control

associated sialorrhea and

hyperhidrosis.

Atropine sulfate

It occurs as colorless crystals or as a

white, crystalline powder.

It is extremely poisonous.

It effloresces in dry air and is slowly

affected by light.

It is an anticholinergic, used in surgery as

an antisialogogue.

Scopolamine or hyoscine

An alkaloid abundant in Datura fastuosa

var. alba and in D. Metel.

It is an ester that, upon hydrolysis, yields

tropic acid and scopoline.

It occurs as an almost colorless, syrupy

liquid from its chloroformic solution and

colorless crystals from its ether solution.

LEVOROTATORY

Scopolamine hydrobromide or hyoscine hydrobromide

It occurs as colorless or white crystals or as a white,

granular powder that is odourless and slightly

efflorescent in dry air. It is extremely poisonous.

It is classified as anticholinergic.

It is employed for preanesthetic sedation and for

obstetric amnesia in conjunction with analgesics

and to calm delirium. It is administered SC or IM in a

single dose.

Hyoscyamus

Also known as Henbane

dried leaf with or without the stem

and flowering or fruiting crop of

Hyoscyamus niger Linné (Fam.

Solanaceae)

It contains not less than 0.04%

alkaloids of hyoscyamus.

Hyoscyamus (a Greek and Latin

name formed from two Greek words,

meaning hog and bean.

The plant is poisonous to swine.

The alkaloids, hyoscyamine and

scopolamine, 0.05% to 0.15% of

which three fourths is hyoscyamine

are the active ingredients.

HYOSCYAMUS

STRAMONIUM

Also known as Jimson weed, Jamestown weed

dried leaf with or

without the stem and

flowering or fruiting

crop of Datura

stramonium Linné

(Fam. Solanaceae)

It yields not less than 0.25% of alkaloids.

Datura (from Sanskrit dhatura, and from

Arabic tatura or tatula, the native name)

Stramonium (from the French word

stramoine meaning stinkweed)

It was used as a “pot herb”

It can serves as atropine

STRAMONIUM SEED

from D. stramonium

The seed contains

0.4% of alkaloids,

principally

hyoscyamine with a

small portion of

scopolamine and

traces of atropine.

It is generally regarded as a noxious weed

and has frequently caused poisoning in

children when seeds were ingested. The chief toxic symptoms are those of

atropine: Dilated pupils Impaired visions Dryness of the skin Secretions Extreme thirst Hallucination Loss of consciousness

COCAINE

Coca leaves or Coca

Dried leaves of

Erythroxylum coca

Lamarck which is

commercially known as

“Huanuco coca” or of E.

truxillense Rusby

“Truxillo coca” (Fam.

Erythroxylaceae)

Erythroxylum (is from the two Greek

words meaning red and wood)

Coca ( is the Spanish name for the tree)

Truxillense (from Truxillo a coastal city

in Peru) Contains three basic types of alkaloids: Derivatives of ecgonine Derivatives of tropine Derivatives of hygrine

Huanuco coca

Contains 0.5 to 1% of ester

alkaloids, derivatives of tropine and

ecgonine

Cuscohygrine is the principal

nonester alkaloid in the leaf.

Truxillo coca

Has lower content of ester alkaloids

but higher percentage of cocaine

(75%)

The shrub was known as “The Divine

Plant of the Incas”

Cocaine hydrochloride

Colorless crystals or as a white,

crystalline powder.

Ingredient in Brompton’s cocktail

Use to control severe pain

CNS stimulant

Administered IV or SC while cocaine free-

based is smoked

Crack

extremely addictive smokable forms

of cocaine processed from cocaine

hydrochloride

Its name refers to the sound made

when rocks of cocaine are smoked.

QUINOLINE ALKALOIDS

These are alkaloids which contain quinoline as their

nucleus including those obtained from cinchona

(quinine, quinidine, cinchonine, and cinchonidine)

Cinchona and its alkaloids are the only members of

this group that are therapeutically important at

present. Cinchonine, is isomeric with cinchonidine

which is the parent alkaloid of the quinine series.

Quinine and its isomer, quinidine, represent 6-

methoxycinchonine.

CINCHONA BARK

Cinchona bark or Peruvian bark

dried bark of the stem or of the root of

Cinchona succirubra Pavon et Klotzch or its

hybrids, known in commerce as red cinchona

or of C. ledgeriana (Howard) Moens et

Trimen, C. calisaya Weddell, or hybrids of

these with other species of Cinchona, known

in commerce as calisaya bark or yellow

cinchona (Fam. Rubiaceae)

Cinchona (named in honor of the

Countess of Chinchon, wife of viceroy of

Peru)

Succirubra (Latin word meaning red

juice)

Calisaya (a tree)

Ledgeriana ( named in honor of

Charles Ledger)

Cinchona toxicity results in temporary loss

of hearing and in impaired sight. Ringing in

the ears is one of the symptoms of toxicity.

When these symptoms are produced as the

result of continuous use of cinchona or of

quinine. The condition has been called

cinchoism.

Cinchona was formerly given in doses of 1g.

CUPREA BARK

obtained from Remijia purdieana Triana and

R. Pedunculata Fluckiger (Fam.Rubiaceae)

it has a copper red color hard , compact, and

heavy it contains numerous transversely

elongated stone cells and 2-6 % of alkaloids of

which 1/3 maybe quinine it’s a commercial

source of quinidine.

CINCHONA ALKALOIDS

Quinidine

It’s a stereoisomer of quinine and is

present in cinchona barks to the extent

of 0.25-1.25%.

It depresses myocardial excitability,

conduction velocity and to a lesser

extent, contractility.

Use to treat various cardiac

arrhythmias such as mature atrial , AV

junctional, and ventricular

contractions : atrial flutter and atrial

fibrilations.

When administered orally, the peak

serum levels are slightly lower with the

gluconate and poylgalacturonate salt

than with sulfate salt .

The usual real dose available is 10 to 20

mg/kg/day in 4 to 6 divided doses in order to

obtain the average therapeutic serum levels

of 3 to 6mcg/ml.

A toxic reaction occurs at levels above

8mcg/ml.

The patient should be instructed to notify the

physician if skin rash,fever,unusual

bleeding/bruising,ringing in the ears,or visual

disturbance occurs.

Quinidine sulfate

sulfate of an alkaloid obtain from cinchona

from Remijia pedunculata or prepared from

quinine.

It occurs as fine needle like white crystals that

frequently cohere in masses.

It is odorless , has a bitter taste and darkens

when exposed to light.

It is readily soluble in water, alcohol, methanol

and chloroform.

Quinidine gluconate

It occurs as a white powder odorless

and has a bitter taste available in

sustained release tablet.

Quinidine polygalacturonate

It affords control and more uniforms

absorptions through the intestinal

mucosa than does quinidine sulfate.

In addition it produces a lower

incidence of GI irritation

Quinine

Diastereoisomer of quinidine

It occurs as white, odourless, bulky

crystals or as a crystalline powder.

It darkens when exposed to light and

effloresces in dry air.

It is freely soluble in alcohol, ether and

chloroform but slightly soluble in water.

Quinine Sulfate

a sulfate of an alkaloid obtained from the

bark of Cinchona species.

A white, odourless, bitter, fine, needlelike

crystals that are usually lusterless.

It becomes brownish when exposed to light.

It is not readily soluble in water, alcohol,

chloroform or ether.

Uses

Antimalarial

For treating of chloroquinine resistant falciparum

malaria combination with pyrimethamine and

sulfadoxine or tetracycline or clindamycin.

It has a skeletal muscle relaxant effect.

It is widely used for the prevention and treatment

of nocturnal recumbency leg cramps.