Alkaloids

What are alkaloids?

They are naturally occurring organic bases that contain nitrogen in a heterocyclic ring and they are mainly derived biosynthetically from amino acids.

They have marked physiological action on man and other animals.

They are found mainly in plants and lesser extent in microorganisms and animals.

Alkaloids are classified based on ?

Botanical source

Pharmacological properties

Molecular structure

Properties of alkaloids

- They are well defined crystalline substances which unite with acids to form salts

- in the plants, they may exist in free state as salts or N-oxides

-apart from elements carbon, hydrogen, nitrogen. Most alkaloids contain Oxygen

- Conine from hemlock and nicotine from tobacco are oxygen free and are liquids

- Colored alkaloids are rare, they are ; berberine is yellow, sanguinarine is copper red

-Alkaloidal substances are often administered as solutions

-the differences in the solubility of alkaloids and their salts provide methods of isolation of alkaloids from plants and separation from non alkaloidal substances present

-Free bases are sparingly soluble in water but soluble in organic solvents, the salts are however soluble in water and sparingly soluble in organic solvents

Nitrogen of Alkaloids can be

Primary (mescaline) , secondary (ephedrine) , tertiary (atropine) , quartenary (one of the N atom in tubocurarine)

Sulphur containing alkaloids

Gliotoxins

Among pteridophytes and gymnosperms , __________ and ____________ alkaloids have medicinal interests

Ephedra and taxus

Alkaloids test by Meyer's reagent (potassiomecuric iodide solution)

Cream colored precipitate

Alkaloids test by Wagner's reagent (solution of iodine in potassium iodide)

Reddish brown precipitate

Alkaloids test by Solution of tannic acid

Yellow precipitate

By Hagers reagent ( saturated solution of Picric acid) or by Dragendorff's reagent (solution of potassium bismuth iodide)

Reddish Brown precipitate

How do you detect caffeine and other purine alkaloids?

Mix with potassium chlorate and a drop of HCL, evaporate to dryness and expose residue to ammonia vapor. A purple color indicates presence of caffeine and purine alkaloids.

This is Murexide test

Colchicine forms ———- color with mineral acids

Yellow

How do you test for Indole alkaloids?

Treat with sulphuric acid and P-dimethylbenzaldehyde, a bluish-violet to red color is observed

Describe the first process of extraction of Alkaloids

The powdered material is moistened with water and mix with lime, which combines with acids , tannins and other phenolic substances.

This sets free the alkaloid if it exist in the plants as salt.

Extraction is carried out with organic solvents like ether, or pet spirit.

Organic liquid is then shaken with Aqueous acid and allowed to separate.

Alkaloidal salts are now in aqueous liquid while many impurities remain behind in organic liquid.

Describe process B of extraction of Alkaloids

Powdered material is extracted with water or aqueous alcohol containing dilute acid.

pigments and other unwanted material are removed by shaking with chloroform or other organic solvents.

Alkaloids are then precipitated by the addition of excess sodium bicarbonate or NH3.

And separated by filteration or extraction with organic solvents

Separation and final purification of mixture of alkaloids may be done by fractional precipitation or distillation of salts eg oxalates, tartrates or picrates.

Volatile liquid alkaloids like nicotine and coniine are isolated by distillation

Volatile liquid alkaloids like nicotine and coniine are isolated by ?

Distillation

Separation and final purification of mixture of alkaloids may be done by?

fractional precipitation or distillation of salts eg oxalates, tartrates or picrates.

Alkaloids derived from L-ornithine

L-ornithine is a non-protein amino acid , in plants .

it is formed mainly from L-glutamic acid

L-ornithine gives two main classes of alkaloids and they are?

Pyrrolidine and Tropane Alkaloids

Tropane alkaloids

(-)hyoscyamine and (-) Hyoscine

Hyoscyamine and Hyoscine are found ?

They are found in varieties of solanaceous plants including Atropa belladonna (deadly night shade) and Datura stramonium ( thorn apple)

Difference between Hyoscyamine and Hyoscine

1) Hyoscyamine is easily racemized than Hyoscine

2) Raceminc form of Hyoscyamine is called Atropine, while that of Hyoscine is called Atroscine or Scopolamine.

Uses of Hyoscine and Hyoscyamine

1) They have antispasmodic effect of the gastrointestinal tract ,

2) They have antisecretory effect controlling saliva secretions during surgical operations.

3) they are used as mydriatics to dilate the pupils of the eye

4) Hyoscine has a depressant action on central nervous system and is used as a sedative to control motion sickness

5) Atropine is a useful antidote for poisoning by acetylcholinesterase inhibitors and organophosphate insecticides

Cocaine

This is a rare alkaloid restricted to some species of Erythroxylum (Erythroxylaceae). Erythroxylum coca is the most prominent as source of cocaine

Uses of Cocaine

1) it is used medicinally as a local anesthetic and as an illegal drug for its euphoric effects

2) it has applications in ophthalmic and in ear, nose and throat surgery

Procaine

It is the first major cocaine analogue employed

Benzocaine

It is used topically but has a short duration of action

Lidocaine

It is an example of an amino amide

analogue and is perhaps the most widely used local

anaesthetic.

It is also used as an anti arrhythmic drug for treatment of ventricular arrhythmia especially after myocardial infarction.

Alkaloids derived from Lysine are

The chief Alkaloid is Lobeline, the minor alkaloid is Lobelanine

Difference between L-Lysine and L-ornithine

1) L-lysine is a homologous of L-ornithine

2) Lysine forms six-membered piperidine rings while L-ornithine forms five-membered pyrrolidine rings.

Lysine alkaloids is found in

Lobelia or Indian tobacco consists of dried leaves and tops of Lobelia inflata (campanulaceae)

Uses of Lobeline

1) it is employed in preparations intended as smoking deterrents

2) The crude plant is used to relieve asthma and bronchitis , but it is quite toxic in large doses

Alkaloids derived from Nicotinic acid include

Nicotine, Anabasine and Nornicotine

Biological source of Tobacco

It is the dried leaves of Nicotiana tabacum (solanaceae)

Tobacco leaves contain ———-% nicotine

0.6-9% and anabasine and nornicotine.

nicotine in small doses acts as

A respiratory stimulant

nicotine in large doses

Cause respiratory depression

Tobacco smoke contains many carcinogens formed by chemicals formed by combustion. They are

Benzpyrene, 2-naphthylamine and 4-amino-biphenyl

uses of nicotine

1) it is used by former smokers who wish to stop the habit

2) it is available in form of chewing gums or nasal sprays or can be absorbed trans dermally from nicotine patches

3) powdered tobacco leaves is used as an insecticide

4) although nicotine is an effective insecticide, it has been replaced by safer agents

5) nicotine can improve memory by stimulating the transmission of nerve impulse

Why is nicotine toxic to man ?

It is toxic due to its effect on the nervous system , interacting with the nicotine acetylcholine receptors

alkaloids derived from tyrosine

Phenyl ethylamines and simple Tetrahydroisoquinoline Alkaloids

Alkaloids derived from tyrosine include

Dopamine, norepinephrine, epinephrine, methyldopa , Carbidopa.

Aromatic hydroxylation and O-methylation reactions in cactus converts dopamine

To mescaline

Biological source of Cactus

Lophophora williamsii (cactaceae)

Cactus plant is used

religious ceremonies to produce hallucinations and establish contact with gods

What is mescaline used for ?

It is used as a hallucinogen in experimental psychiatry

It causes unusual and bizarre colored images

Treatments with L-DOPA help to?

Increase dopamine levels in the brain

Dopamine can cross the blood brain barrier. True or False?

False

Dopa can cross the blood-brain barrier true or false

True

To administer Dopa, what must be done?

It must be administered with a Dopa-decarboxylase inhibitor.

Carbidopa to prevent rapid decarboxylation in the bloodstream.

Use of Noradrenaline

Noradrenaline is a powerful peripheral vasoconstrictor predominantly acting on ex-adrenergic receptors

It is used in restoring blood pressure in acute hypotension

Methyldopa is used for

hypertension

Methyl dopa competes with noradrenaline true or false ?

True

Injections of adrenaline is of value in cases of?

Cardiac arrest or in allergic emergencies such as bronchospasm or anaphylactic shock

Adrenaline is effective orally true or false

False

The most important constituent in menispermaceous curare is

Bis-benzyltetrahydroisoquinoline alkaloid tubocurarine

Biological source of tubocurarine

Chondodendron tomentosum Menispermaceae

Tubocurarine is antagonized with

Neostigmine

Tubocurarine is injected as

A muscle relaxant in surgical operations, reducing the need for deep anesthesia

Principal opium alkaloids are

Morphine, codeine , and thebaine

Biological source of morphine, cocaine and thebaine

Papaver somniferum (papaveraceae)

Morphine

It is a powerful analgesic and narcotic, it is one of the most valuable analgesics for relief of severe pain.

It induces a state of euphoria and mental detachment together with nausea, vomiting, constipation , tolerance and addiction

It leads to physical dependence, which is difficult to overcome, which is why it is used for the relief of terminal pain.

Codeine

It is the 3-0 methyl ether of morphine and is the most widely used of the opium alkaloid.

It is taken orally and is a component of many analgesic preparations

It is less addictive, medium analgesic but is still too constipating for long term use.

It has valuable antitussive action, helping to relieve and prevent coughing

What makes thebaine different from morphine/codeine

Thebaine possesses a conjugated diene ring system

Thebaine is almost devoid of

Analgesic activity, but may be used as morphine antagonist

Papaverine

It is a benzylisoquinoline alkaloid and it is structurally different from morphine, codeine, and thebaine

It has little or no analgesic or hypnotic properties but possess spasmolytic and vasodilator activity

Uses of Papaverine

1) papaverine is used in some expectorant preparations

2) it is used in the treatment gastrointestinal spasms

3) it is used as an effective treatment for male impotence, it is administered as direct injection to achieve erection of the penis

Noscapine

Noscapine has good antitussive and cough suppressant activity , but no analgesic or narcotic action.

It was formerly called narcotine but was changed to Noscapine to reflect its lack of narcotic action

Phenethylisoquinoline alkaloid

Colchicine

Biological source of Colchicine

Colchicum autumnale (Liliaceae /colchicaceae)

Extracts of colchicum autumnale and later colchicine have used for ?

The treatment of gout

Terpenoid tetrahydroisoquinoline alkaloids are

Alkaloids found in ipecacuanha

Biological source of ipecacuanha

Dried rhizomes and roots of Cephaelis ipecacuanha (Rubiaceae)

Ipecacuanha has a long history of use in the treatment of

Amoebic dysentery

————- and ————- provide unusual sample of tetrahydroisoquionoline alkaloids

Emetine and cephaline

Ipecacuanha emetic mixture is an important preparation used for ?

Treatment of drug overdose or poisoning. It is a standard component in poison antidote kit

Uses of Terpenoid tetrahydroisoquinoline alkaloids

1) Ipecacuanha has expectorant activity

2) emetine and cephaline are both potent inhibitors of protein synthesis

3) they display anti tumor and antiviral, as well as anti amoebic activity, but toxic for therapeutic use

Alkaloids derived from tryptophan

Terpenoid indole alkaloids

terpenoid indole alkaloids is gotten from

Rauwolfia

Botanical source of Rauwolfia

Rauwolfia serpentina Apocyanaceae

Rauwolfia is used as

an antidote to snake-bite, to remove white spots in the eyes, against stomach pains, fever, vomiting, and headache, and to treat insanity

Rauwolfia contains a wide range of indole alkaloids, but principally they are;

Reserpine, Rescinnamine and deserpidine

Other alkaloids of note in Rauwolfia are

Serpentine, ajmaline, ajmalicine

Uses of Rauwolfia alkaloids

1) Reserpine and deserpidine have been widely used as antihypertensives and mild tranquillizers.

2) Ajmalicine is employed as an antihypertensive while ajmaline is of value in the treatment of cardiac arrhythmias

3) Rauwolfia alkaloids are now hardly ever prescribed either as antihypertensives or as tranquilizers.

Over a period of a few years, they have been replaced by synthetic alternatives.

Other source of terpenoid indole alkaloids is

Catharanthus

Biological source of catharanthus

Catharanthus roseus (Apocynaceae)

Catharanthus alkaloids

vinblastine, vinleurosine, vinrosidine, and vincristine.

Uses of Catharanthus alkaloids

1) Vinblastine is used mainly in the treatment of Hodgkin's disease, a cancer affecting the lymph glands, spleen, and liver.

2) Vinscristine has superior antitumor activity compared to vinblastine but is more neurotoxic.

3) Vincristine is Clinically more important than vinblastine, and is especially

useful in the treatment of childhood leukaemia giving a high

rate of remission.

4) Some other cancer conditions, including Iymphomas, lung cancer, and cervical and breast cancers, also respond favourably.

Alkaloids derived from Histidine

Imidazole alkaloids

Imidazole alkaloids is

Pilocarpine from Pilocarpus jaborandi (jaborandi)

uses of pilocarpine

Its salts are valuable in ophthalmic practice and are used in eyedrops as miotic and for the treatment of glaucoma.

Ergot Alkaloids are derived from

The fungus Claviceps purpurea (Clavicipitaceae)

Ergot alkaloids are derivative of —————acid

D-lysergic acid

Ergot alkaloids include

Ergotamine and Ergometrine

Uses of Ergot Alkaloids

1) Ergometrine is used as an oxytocic and is injected during the final stages of labour and immediately following childbirth especially if hemorrhage occurs.

2) Reduces bleeding due to its vasoconstrictor effect

3) Ergotamine is a partial agonist of x-adrenoceptors and 5-HT receptors. It is used in treatment of acute attacks of migraine.

Quinoline alkaloids are

quinine, quinidine, cinchonidine, cinchonine

Quinoline alkaloids are examples of

Terpenoid indole alkaloid modifications

Quinoline alkaloids are found in

Cinchona succirubra (Rubiaceae)

Uses of Quinoline alkaloids

1) Quinidine is the principal alkaloid used therapeutically and is used to treat cardiac arrhythmias.

2) Quinidine, cinchonine and cinchonidine also have antimalarial properties but not as effective as quinine.

3) Cardiac effect makes quinidine unsuitable as an antimalarial.

Another example of Quinoline containing structure is

Camptothecin