ALKALOIDS

Presented By M,S.Riyazullah M.Pharm

Associate Professor

Department of PharmacognosyKrishna Teja Pharmacy college

Subject code: 15R00402

(Pharmacognosy-II)

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 precipitate

Reagent used: Wagner’s Reagent [Solution of

iodine in potassium iodide]

Mayer’s Test

(+) Cream color precipitates

Reagent 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 areclassified 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 tinctureinclude:

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

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.

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.