Alkaloids

Alkaloids-Introduction and Drugs

1. 1.Vinca
2.Rauwolfia
3.Belladonna
4.Opium
By-Maninderjit kaur
Rayat-Bahra Institute of Pharmacy, Hoshiarpur

2. Theterm“alkaloid”(alkali-like)iscommonlyusedto
designatebasicheterocyclicnitrogenouscompoundsofplant
originthatarephysiologicallyactiveandgenerallypossessing
amarkedphysiologicalactiononmanoranimalseveninsmall
quantities
The nitrogen is usually contained in a heterocyclic ring system
and it mainly derived from amino acids

4. CLASSIFICATION
There are three main types of alkaloids:
(1) True alkaloids
(2) protoalkaloids and
(3) pseudoalkaloids.
True alkaloids and protoalkaloids are derived from
amino acids,
whereas pseudoalkaloids are not derived from these
compounds.

5. Truealkaloidsderivefromaminoacidandtheysharea
heterocyclicringwithnitrogen.
Thesealkaloidsarehighlyreactivesubstanceswithbiological
activityeveninlowdoses.
Alltruealkaloidshaveabittertasteandappearasawhitesolid,
withtheexceptionofnicotinewhichhasabrownliquid.
Truealkaloidsformwater-solublesalts.
Moreover,mostofthemarewell-definedcrystallinesubstances
whichunitewithacidstoformsalts.
Truealkaloidsmayoccurinplants(1)inthefreestate(2)as
saltsand(3)asN-oxides.Examplesoftruealkaloidsinclude
suchbiologicallyactivealkaloidsascocaine,quinine,dopamine
andmorphine.

6. Protoalkaloids or Biological amines
Protoalkaloids are compounds, in which the N atom derived from an amino acid
is not a part of the heterocyclic ring system. Nitrogen is present in side chain eg
Ephedrine, mescaline and yohimbine
Such kinds of alkaloid include compounds derived from L-tyrosine and L-
tryptophan.
Pseudoalkaloids
Pseudoalkaloids are compounds, the basic carbon skeletons of which are not
derived from amino acids.
These are not derived from amino acids but have nitrogen in a heterocyclic ring.
These alkaloids can also be derived from nonamino acid precursors. The N atom
is inserted into the molecule at a relatively late stage, for example, in the case of
steroidal or terpenoid skeletons.
Examples of pseudoalkaloids include such compounds as caffeine and theobromine,
chlorogenic acid

7. QUALITATIVE CHEMICAL TESTS FOR ALKALOIDS
General tests answered by all alkaloids are as follows:
Dragendorff’sTest
Drug solution + Dragendroff’sreagent (Potassium Bismuth Iodide),
formation of Orange red colour
Mayer’s Test
Drug solution + few drops of Mayer’s reagent (potassium mercuric iodide),
formation of creamy-white precipitate
Hager’s Test
Drug solution + few drops of Hagersreagent (Saturated aq. Solution of
Picric acid), formation of crystalline yellow precipitate
Wagner’s Test
Drug solution + few drops of Wagner’s reagent (dilute Iodine solution),
formulation of reddish-brown precipitate
Tannic Acid Test
Drug solution + few drops of tannic acid solution, formation of buff
colouredprecipitate

8. Physical Properties:
I-State:
◦Most alkaloids are crystalline solids.
◦Few alkaloids are amorphous solids e.g. opium
◦Some are liquids that are either:
Volatile e.g. nicotine and coniine, or
Non-volatile e.g. pilocarpineand hyoscine.
II-Color:
The majority of alkaloids are colorless but some are
colored e.g.:
◦Colchicineand berberineare yellow.
◦betanidineis orange.
The salts of sanguinarineare copper-red

9. III-Solubility:
Both alkaloidalbases and their salts are soluble in
alcohol.
Generally, the bases are soluble in organic solvents and
insoluble in water
Exceptions:
Bases soluble in water: caffeine, ephedrine, codeine, colchicine,
pilocarpineand quaternary ammonium bases.
Bases insoluble or sparingly soluble in certain organic solvents:
morphine in ether, theobromineand theophyllinein benzene.
Salts are usually soluble in water and, insoluble or
sparingly soluble in organic solvents.
Exceptions:
Salts insoluble in water: quinine monosulphate.
Salts soluble in organic solvents: lobelineand apoatropine
hydrochlorides are soluble in chloroform

10. IV-Isomerization:
Opticallyactiveisomersmayshowdifferentphysiological
activities.l-ephedrineis3.5timesmoreactivethan
d-ephedrine.
l-ergotamineis3-4timesmoreactivethand-ergotamine.
d-Tubocurarineismoreactivethanthecorrespondingl-form.
Quinine(l-form)isantimalarialanditsd-isomerquinidineis
antiarrythmic.
Theracemic(opticallyinactive)dl-atropineisphysiologically
active.

11. Chemical Properties
Most of the alkaloids are basic in nature, due to the availability of
lone pair of electrons on nitrogen.
The basic character of the alkaloid compound is enhanced if the
adjacent functional groups are electron releasing.
The alkaloid turns to be neutral or acidic when the adjacent functional
groups are electron withdrawing like amide group which reduces the
availability of the lone pair of electron.
Their salt formation with an inorganic acid prevents many a time their
decomposition.
In the natural form, the alkaloids exist either in Free State, as amine or
as salt with acid or alkaloid N-oxides.

12. N
N
NN
H
N
H
N
NH
Me
N
Tropane
N
H
N
NN
NH
PiperidinePyridinePyrrolidine Quinoline
Isoquinoline PurineImidazoleIndole
NH
Tetrahydro-
isoquinoline

13. ◦Narcotic analgesic e.g.Morphine
◦Antimalarial e.g. Quinine
◦Reflux excitability e.g.Strychnine
◦Respiratory stimulant e.g.Lobeline
◦Neuralgia e.g. Aconitine
◦Oxytocic e.g. Erogotometrine
◦Bronchodilator e.g. Ephedrine, vasicine
◦Anticholinergic e.g. Atropine
◦CNS stimulant e.g. Caffeine
◦Antitussive e.g. Codeine
◦Antiarrythmic e.g.Quinidine
◦Antihypertensive e.g. Reserpine
◦Anticancer e.g. Vincristine
◦Antiglucoma e.g. Pilocarpine


14. Synonyms:Vincarosea,Catharanthus, Madagascar periwinkle
Biological Source
Vinca is the dried entire plant of Catharanthus roseusLinn., belonging
to family Apocynaceae.
C.C.TheimportantalkaloidsinCatharanthusarethedimerindole
indolinealkaloidsVinblastineandVincristineandtheypossessdefinite
anticanceractivity.VindolineandCatharanthineareindolemonomeric
alkaloids.Italsocontainsmonoterpenes,sesquiterpene,indoleand
indolineglycoside.
Use:It's cytotoxic used for hodgkins and non hodgkins disease.
Vinblastin is an antitumour alkaloid used in the treatment of Hodgkin’s
disease.
Vincristine is a cytotoxic compound and used to treat leukaemia in
children.
Anticancer single or combination therapy.
M.O.A:bind to protein (tubulin) which inhibits mitosis in
microtubules.

16. Synonyms
Sarpagandha, Chandrika; Chootachand; Indian snake root.
Biological Source
Rauwolfia consists of dried roots of Rauwolfia serpentinaBenth.,
belonging to family Apocynaceae.
ChemicalConstituents:Itcontainsabout0.7–2.4%total
alkaloidalbasesfromwhichmorethan80alkaloidshavebeen
isolated.Theprominentalkaloidsisolatedfromthedrugare
reserpine,rescinnamine,ψ-reserpine,rescidine,raubescineand
deserpidine.
Theotheralkaloidalcomponentsareajmalinine,ajmaline,
ajmalicine(8-yohimbine),serpentine,serpentinine,
tetrahydroreserpine,raubasine,reserpinine,isoajamalineand
yohambinine.

17. Uses
Rauwolfiainusedashypnotic,sedativeand
antihypertensive.
Itisspecificforinsanity,reducesbloodpressureand
curespainduetoaffectionsofthebowels.
Itisgiveninlabourstoincreaseuterinecontractions
andincertainneuropsychiatricdisorders.
Ajmaline,whichhaspharmacologicalproperties
similartothoseofquinidine,ismarketedinJapanfor
thetreatmentofcardiacarrhythmias.

18. Marketed Products
It is one of the ingredients of the preparations known as
Confido, Lukol, Serpina (Himalaya Drug Company)
and Sarpagandhan bati (Baidyanath).

19. Synonyms
Belladonnaherb;Belladonnaleaf;Deadlynightshadeleaves;Banewort;
Death’sherb,Dwale;Poisonblackcherry;Foliabelladonnae.
BiologicalSource
BelladonnaconsistsofdriedleavesandfloweringtopsofAtropa
belladonnaLinn.(EuropeanBelladonna),belongingtofamilySolanaceae.
Itcontainsabout0.35%oftotalalkaloidscalculatedashyoscyamine.
•Main Alkaloids are:
 1-Atropine.
 2-Hyoscyamine.
 3. Hyoscine(Scopolamine).
Hyoscyamineis the major natural alkaloid with negative optical rotation (l-
form).
During extraction hyoscyamineracemizesto the optically inactive dl
Atropine.
Both alkaloids composed of tropinebase and tropic acid

20. Uses
Thedrugisusedasadjunctivetherapyinthetreatmentof
pepticulcer;
functionaldigestivedisorders,includingspastic,mucousand
ulcerativecolitis;diarrhoea,andpancreatitis.
Duetoanticholinergicproperty,itisusedtocontrolexcess
motoractivityofthegastrointestinaltractandspasmofthe
urinarytract.
Decreasemotilityofsmoothmusclessousedas
antispasmodics.
ConsumptionofBelladonnachecksexcessiveperspirationof
patientssufferingfromtuberculosis.
Belladonnaactsasaparasympatheticdepressant.
Marketed Products
It is one of the ingredients of the preparation known as Belladona
plaster (SurgiPharma) for backache, stiffness of muscles and boil,
swollen joints.

21. Synonyms: Crude Opium; Raw Opium; Gum Opium; Afim; Post.
Biological Source: Opium is the air dried milky latex obtained by incision
from the unripe capsules of Papaver somniferumLinn, or its variety P.
album Decand., belonging to family Papaveraceae.
Opium is required to contain not less than 10% of morphine and not less
than 2.0% of codeine. The thebaine content is limited to 3%.
C.C: The alkaloids are combined with meconic acid.
Theotheralkaloidsisolatedfromthedrugarecodeine(0.8–2.5%),narcotine,
thebaine(0.5–2%).noscapine(4–8%),narceineandpapaverine(0.5–
2.5%).Morphinecontainsaphenanthrenenucleus
Thedrugalsocontainssugars,sulphates,albuminouscompounds,colouring
matterandmoisture.

22. Uses
Opium and morphine have narcotic, analgesic and sedative
action and used to relieve pain, diarrhoea dysentery and
cough.
Poppy capsules are astringent, somniferous, soporific, sedative
and narcotic and used as anodyne and emollient.
Codeine is mild sedative and is employed in cough mixtures.
Noscapine is not narcotic and has cough suppressant action
acting as a central antitussive drug.
Papaverine has smooth muscle relaxant action and is used to
cure muscle spasms.
Opium, morphine and the diacetyl derivative heroin, cause
drug addiction.

23. Codeine
MorphineHeroine
Pappaverine Noscapine
(Narcotine)
Thebaine:
6-methoxy codeine