alkaloids 2.pdf pharmacognosy pharmacy student

Alkaloids

1. BpharmYear 3
PHM 3160 :
General
Pharmacognosy
Alkaloids
Martha Chulu Mussa
B.PHARM, M.CLIN PHARM, PhD Candidate(Pharmacognosy)
School of Health Sciences
Levy MwanawasaMedical University

2. ALKALOIDS

6. Occurrence& Distribution of Alkaloids
•Alkaloidshaveawidedistribution,beingpresentinplants,fungi,
bacteria,amphibia,andanimals.
•Truealkaloidsareofrareoccurrenceinlowerplants.
•Occurinbacteria(Pseudomonasaeruginosa)andfungi,e.g.
Ergotamineandergometrinefromergotfungus.
•Amphibians:Nearly300alkaloidsbelongingtomorethan24
classesareknowntooccurintheskinsofamphibiansalongwith
othertoxins.Theyincludethepotentneurotoxicalkaloidsoffrog
ofgenusPhyllobates,whichareamongthemostpoisonous
substanceknown.

25. Structure and classification
•Alkaloidsshowgreatvarietyintheirbotanicalandbiochemicalorigin,in
chemicalstructureandinpharmacologicalactions.Consequently,many
differentsystemsofclassificationarepossible.
Therearetwobroaddivisions:
•Non-heterocyclicoratypicalalkaloids,
•sometimescalledproto-alkaloidsorbiologicalamines.
•theyaresimpleaminesorbiologicalamines,
•containnitrogenatominthesidechain,
•basicinnature,
•Examples:mescalineandephedrine.
•Heterocyclicortypicalalkaloids,dividedinto14groups
accordingtotheirringstructure.

26. Heterocyclic alkaloids types:
1.Pyrroleand pyrrolidine
2.Pyrrolizidine
3.Pyridine and piperidine
4.Tropane
5.Quinoline
6.Isoquinoline
7.Aporphine
8.Quinolizidine
9.Indoleor benzopyrrole
10.Indolizidine
11.Imidazoleor glyoxaline
12.Purine(pyrimidine/imidazole)
13.Steroidal (some combined as glycosides)
14.Terpenoid

43. •potassium
bismuth iodide
solution
•Observation :
orange colored
precipitate
•iodine in
potassium
iodide
•Observation :
red-brown
precipitate
•mercuric
potassium iodide
solution
•Observation:
white precipitate
•picric acid
•Observation :
yellow
precipitate
HAGERS
REAGEN
T
MAYER
‘S
REAGEN
T
DRAGEN
DORFF'S
REAGEN
T
WAGNER
’S
REAGEN
T

45. Protoalkaloids
•The alkaloids in this group do not contain heterocyclic
nitrogen atoms.
•Many of them are simple derivatives of phenyl ethyl amine.
•They are not restricted to any particular class of alkaloids and
are often classified according to the amino acids from which
they are derived.
•The drugs and their alkaloids classified as alkaloidalamine
are:
Ephedra ephedrine, pseudoephedrine
Colchicum corm colchicine
Khat cathinone

49. Actions:
Ephedrine is potent sympathomimetic similar to adrenaline that
stimulates adrenergic receptors.
Mechanism of action: It excites the sympathetic nervous system,
causes, vasoconstriction and cardiac stimulation and produce
effect similar to those of Epinephrine. It produces rise in blood
pressure and causes mydriasis. CHCHCH
3
NHOH CH
3
Ephedrine
CHCH
2
NHOH CH
3
HO
HO
Adrenaline
* *

51. Uses:
The drug present as Ephedrine sulfate used:
•To treat hypotensive states.
•For local treatment of nasal congestion
•For allergic disorders as bronchial asthma and hay fever
•Its action is more prolonged than that of adrenaline, and it
has the further advantage that it need not be given by
injection but may be administered by mouth.

54. O
OCH
3
H
NHCOCH
3
H
3CO
H
3CO
colchicine
OCH
3

56. Khat
•Thisconsistsofthefreshleavesof
Cathaedulis(Celastraceae).
•Theplantiscultivatedinpartsofeast
andsouthernAfrica,andinsouthern
Arabia.
•Itstraditionaluseissimilartothatof
cocainthatthefreshleaves,when
chewed,haveastimulatoryeffectwith
thealleviationofdepressionandofthe
sensationsofhungerandfatigue.

57. Khatcontains a potent phenylalkylaminealkaloid ( -) Cathinone. NH
2
CH
3
O
( -) Cathinone
( -) Cathinonehas pharmacologic properties similar to amphetamine, and is of similar
potency with a similar mechanism of action.
They induce catechol amine release from storage site, so it cause euphoria and habit
formation.

58. Khat–Uses and Actions
Traditionally: Fresh leaves are chewed and used to elevates
mood, increases mental and physical activity
Used by students & labourers.
Used to treat depression (brings about a sense of well-being)
Alleviates sensations of hunger and fatigue.
CNS stimulant activity
Abused drug

60. Thepurinesareconsistingofasix-memberedpyrimidinering
fusedtoafive-memberedimidazolering.
threewell-knownexamplesare:
•Caffeine(1,3,7-trimethylxanthine),
•Theophylline(1,3-dimethylxanthine)
•Theobromine(3,7-dimethylxanthine).
Botanicalorigin:
Coffeaarabica
Colanitida xanthine
TheobromaCocoaseeds
Taeleaves(camillasinensis)
Purine alkaloids

69. Cola, Kola
•kolanutisthedriedcotyledonofcolanitidaorotherspecies(F.
sterculiaceae).
•Kolanutscontaincaffeineupto3.5%and1%oftheobromine.
Uses:
•Kolapossecentralstimulantactionofcaffeine.
•Principaluseisinmanufactureofnonalcoholiccarbonatedbeverages

70. •Cocoaseeds(CocoaBeans)areobtainedfrom
Theobromacacao(Sterculiaceae),atreeusually4-6m
high.
•CocoaisproducedinSouthAmerica,CentralAmerica,the
WestIndies,WestAfrica.
Constituents:
•Cocoaseedscontain0.9-3.0%oftheobromine
•Theseedsalsocontain0.05-0.36%caffeine,cocoafator
butter.
•Thefreshseedscontainabout5-10%ofwater-soluble
polyphenols(epicatechol,leucoanthocyaninsand
anthocyanins)
Cocoa seed

71. Caffeine:
1, 3, 7-trimethyl xanthine occur in coffee, tea, cacao and kola
usually prepared from tea or recovered from coffee roasters.N
N
N
N
H
3C
CH
3
CH
3
O
O

72. Pharmacological Activity of Caffeine
•CNS stimulant activity:
1.Enhances alertness,
2.Facilitates thought formation,
3.Decreases the sensation of fatigue.
•Stimulates respiratory centre of the
brain (increasing sensitivity to
CO2).
•Cardiovascular activity:
1.Positive inotropic action,
2.tacchycardia,
3.slight peripheral dilation,
4.mild diuretic action

73. Caffeine: Uses
•Incombinationswithantipyreticsandanalgesics,coldandflu
medication.Toincreasestheintestinalabsorptionofsomeof
thesedrugs;ortocounteractdrowsiness.
•Ingredientinnon-alcoholicbeveragesand“energizing”
beverages

74. Side effects of caffeine
Sinus tacchycardia
Epigastricpain
Nausea
Vomiting
Nervousness
Insomnia
tremors

75. Theophylline
Theophyllineor1,3,-dimethylxanthine.
PharmacologicalActionofTheophylline:
Bronchialsmoothmusclerelaxant
Stimulatesrespiratorycenterinthebrainstembyincreasingsensitivity
toCO2.
CNSstimulating
Slightlyinotropic.
Diureticactivityisstrongerthanthatofcaffeine.

76. Uses:
Theophylline utilized principally as smooth muscle
relaxants for :
•The symptomatic relief or prevention of bronchial
asthma .
•Treatment bronchospasm associated with chronic
bronchitis and emphysema
•Cough & reversible bronchospasm
(chronic obstructive pulmonary disease)

77. Theobromine
3, 7-dimethyl xanthine obtained from dried ripe seed of theobromacacao ( F.
strerculiaceae) HN
N
N
N
CH
3
O
O
CH
3
.
Cocoa has nutritive, stimulant and diuretic properties.
Theobromineis used as a diuretic.
It has less action on the CNS than caffeine.
Oil of theobromais used in pharmacy chiefly as a
suppository base.
uses

81. Deadly nightshade
Atropabelladonna
Botanical Name: Atropabelladonna
Family: Solanaceae
Chemical Constituents: Belladonna leaf contains 1% of total alkaloids. About
75% of alkaloids are hyoscyamine and the remainder is atropine 25%. It also
contains small quantities of pyridine, N-methyl pyrroline, scopolamine, calcium
oxalate, apo-atropine, 14% acid soluble ash and 4% acid insoluble ash.
Uses
1. Belladonna leaves are used as sedatives, anticholinergic and narcotic.
2. It is used as an adjunct therapy in the treatment of peptic ulcer and also in
pancreatitis, ulcerative colitis and diarrhea.
3. Belladonna acts as a local anesthetic.
4. It acts as a spasmolytic agent.
5. Atropine is used as to dilate the pupil of the eye. It degrades slowly, typically
wearing off in 2 to 3 days, so tropicamide (a synthetic shorter-acting cholinergic
antagonist) is generally preferred as a mydriatic. The effects of atropine can last up
to two weeks.

86. Coca: Erythroxylumcoca
Name : Coca leaf/Cocaine
Botanical Name: Erythroxylumcoca
Family: Erythroxylaceae
Chemical Constituents: Coca leaves contain 0.7 –1.55 of total alkaloids
and there are three basic types of alkaloid in coca leaves. 1. Ecgonine
derivatives: Cocaine, Cinnamyl cocaine. 2. Tropine derivatives: Tropa
cocaine, Vallerine. 3. Hygrine derivatives: Hygroline, Cuscohygrine. Uses
1. Coca leaves are used as astringent and CNS stimulant.
2. Cocaine is used as local anesthetics.
3. Cocaine hydrochloride is used to control severe pain associated with
cancer.
4. Coca is a stimulant toxic

87. Cocaine
Prepared semisyntheticallyfrom of ecgonine
Adrenergic stimulant, local anaestheticcause addiction

88. Alkaloid chemistry: crack cocaine
Base (alkaloid) + acid alkaloid salt + water
e.g. Morphine + sulphuric acid morphine sulphate +
water
Cocaine base + HClcocaine HCl+ water
But a weak acid or base is displaced by a stronger one….. so
Cocaine HCl+ stronger alkali (e.g. NaHCO
3) cocaine
base (crack) + salts + water
To make crack, ‘powder’ cocaine the salt is dissolved in a
mixture of water and either ammonia or sodium bicarbonate
(baking soda) added. The mixture is boiled to separate out
the solid, and then it's cooled. The solid is then dried and cut
up into small nuggets, or "rocks."
Although crack cocaine is a form of non-ionic cocaine,
because production doesn't require the use of flammable
solvents, it is safer to make than ‘freebase’

89. Alkaloid chemistry: making crack (base) cocaine
from the salt
Step 1 (left): Dissolving powder cocaine in hot water
Step 2 (right): Adding sodium bicarbonate to the mixture

Step 5: Filtering the cooled mixture–
Step 3 (left): Boiling the solution to separate out the solids
Step 4 (right): Cooling the separated mixture

91. Rauwolfiaserpentine
•Rauwolfiaconsistsofthedriedrhizomeand
rootsof Rauwolfiaserpentiana.
(Apocynaceae),asmallshrubfoundin
India,Pakistan,BurmaandThailand
Constituents
Rauwolfiacontainsatleast30alkaloidswhich
totalsome0.7-2.4%,e.g.:
oajmaline,(rauwolfine)
oajmalinine
oajmalicin
oserpentine
oserpentinine
oThechieftherapeuticallyimportantalkaloids
arereserpine.
•Othersubstancespresentinclude
phytosterols,fattyacids,unsaturatedalcohols
andsugars.

96. •is the dried whole plant of catharanthusroseus. F. Apocynaceae.
•Folklore uses as an oral hypoglycemic agent.
•It contain 150 alkaloids, the most important are the anticancer
agents vincristine and vinblastine.
•These are complex bisindole(dimericindole) natural products
present in small quantities in the plant material.
•
CatharanthusOr Vinca

97. Actions and uses
•Vincristineandvinblastinearemitoticinhibitors,arrestcell
divisionatmetaphase.
•Theyactbybindingtotheproteintubulininthemitotic
spindle,preventingpolymerizationandassemblyinto
microtubule,thusstoppingthecellfromseparating
itschromosomesduringthemetaphase;thecellthen
undergoesapoptosis.
•Vinblastine is used mainly for the treatment of generalized
Hodgkin's disease and non-Hodgkin's lymphomas.
•Vincristine is used principally in the treatment of acute
lymphocytic leukaemiain children. It has other applications
for lymphomas, small cell lung cancer cervical and breast.
•Vincristine has a superior antitumor activity compared to
vinblastine but is more neurotoxic

98. N
N
H
HO
COOCH
3
COOCH
3
CH
2CH
3
H
3CO
N
H
N
COOCH
3
R
OH
CH
2CH
3
H
.H2SO4
R= CH3 Vinblastine sulfate
R= CHO Vincristine sulfate

100. Uses
•Theactionofthewholedrugcloselyresemblesthatof
strychnine.Thealkaloidwasformerlyusedasacirculatory
stimulantinsuchcasesassurgicalshock,butitsuseisnow
morelimitedtothatofarespiratorystimulantincertaincasesof
poisoning.
•Likeotherbitters,strychnineimprovestheappetiteanddigestion,
butithasbeenconsiderablymisusedasageneraltonic.
•Brucine:Islesstoxicthanstrychnineandusedcommerciallyas
analcoholdenaturant

101. Calabarbeans Is dried ripe seed of physostigmavenenosum(F. leguminosae) ‘
Constituents :
Contain several alkaloids :
Physostigmine(eserine),
eseramine,
geneserine.
Isophysostigmine
physovenine,
Norphysostigmine
Calabatineand calabacine

102. •The structure of geneserine, long regarded as an
N-oxide, has been revised to include the oxygen
in a ring system.
•The chief alkaloid, physostigmine, is present to
the extent of about 0.15%.
•It is derived from tryptophan.
•On exposure to air it oxidizes into a red
compound, rubreserine, and should therefore be
protected from air and light.
•The official salt, the salicylate, is more stable
than the sulphateand is non-deliquescent.

103. Actions and uses of Physostigmine
or eserine:
•ItreversiblyinhibitsAChE(cholineesterase)andenhance
theeffectofendogenousacetylcholine.
•Physostigminesalicylateisusedforcontractingthepupilof
theeye,oftentocombattheeffectofmydriatics
•Physostigmineisusedinthetreatmentofoverdosesof
drugswithanticholinergicactions,suchasatropine.
•Ithasalsobeeninvestigatedasanintravenousinjectionfor
reversingtheeffectsofanumberofsedatives.
•ForAlzheimer'sdisease:ithasshownsomeevidenceof
inducingaslightimprovementinintellectualandcognitive
performance.

104. Ergot alkaloids
•Ergot(ErgotofRye)isthedriedsclerotiumofa
fungus,Clavicepspurpurea(Clavicipitaceae),
arisingintheovaryoftherye,Secalecereale.
Controlledfieldcultivationonryeisthemain
sourceofthecrudedrug.

116. Uses
•Althoughwholeergotpreparationsweretraditionallyusedin
labourtoassistdeliveryandtoreducepost-partumhemorrhage,
ergotitselfhasbeenlargelyreplacedinthepharmacopoeiasby
theisolatedalkaloids.
•Onlyergometrineproducesanoxytociceffectergotoxineand
ergotaminehavingquiteadifferentaction.
•Ergometrineissolubleinwaterorindilutealcohol.Itisoften
known,particularlyintheUSA,asergonovine
•Ergotamineandthesemisyntheticdihydroergotaminessaltsare
employedasspecificanalgesicsforthetreatmentofmigraine.
•Druginpharmacy:ergotamineandusedwithcaffeinefor
treatmentofmigraineheadachebothactascerebral
vasoconstrictors.
•Lysergicaciddiethylamide(LSD-25),preparedbypartial
synthesisfromlysergicacid,isapotentspecific
psychotomimetic,causeCNSstimulationanditisdrugofabuse
.

127. QUINOLINE ANDISOQUINOLINE
ALKALOIDS

128. QuinolineAlkaloids

129. QuinolineAlkaloids
Alkaloids containing quinolineas their basic nucleous.
Cinchona and its alkaloids are only members of this group that are
therapeutically important at present.
Consist of alkaloids and alkaloid salts obtained from the bark of certain
Cinchona species :
•Quinine and Quinidine,
•Cinchonineand Cinchonidine.
•CinchonaalkaloidsarepresentassaltswithQuinicand
Cinchotannicacids

136. Toxicity
Over doses of cinchona products results in:
1. Temporary loss of hearing.
2. In impaired sight.
3. Ringing in the ear.
This symptom of toxicity condition has been
called cinchonism

137. Isoquinolinealkaloids

138. Isoquinolinealkaloids :
•The isoquinolinestructure occurs in a considerable member of alkaloids,
widely distributed in plant families.
•The important alkaloids in this group are:
1.Ipecac : emetine, cephaeline,psychotrine
2.Curare: D. tubocurarine
3.Opium and its alkaloids.

139. Ipecac Alkaloids
•dried root or rhizome of Cephaelis
ipecacuanhaof the Rubiaceaefamily.
•It should contain at least 2% alkaloids.
•Constituents: Ipecacuanhacontains the
alkaloids :
emetine,
cephaeline,
psychotrine,
psychotrinemethylether
•emetamine.
These are isoquinolinederivatives.

140. IpecacuanhaUses
1.Ipecac in the form of syrup is used in the treatment of
drug over dose and in cases of poisonings. It produces
emesis through a local irritant effect on the GI mucosa
and a central medullary effect, by stimulation of the
chemoreceptor trigger zone.
2.Expectorant
3.Treatment of Amoebic Dysentery
Emetine (methyl cephaline) is antiamebic
Emetine is more expectorant and less emetic in action
than cephaeline, and is added to many cough medicines.
Psychotrineand its O-methyl ether are selective
inhibitors of human immunodeficiency virus and their
study could lead to the development of therapeutically
useful agents.

142. Curare alkaloids
Tubocurarine:
•Has a bisbenzylisoqinoline structure.
•It is obtained from the bark and stems of Chondrodendrumtomentosum(
family Menispermaceae)
.
•The term 'curare' is a generic one applied to various South American
arrow poisons, because crude extract prepared from different species was
used by certain natives of the Amazon regions of South America as arrow
poison, which kills by paralysis of the muscles required to breathe .
Tubocurarinechloride

143. uses
Tubocurarinechlorideisemployedas:
1.Askeletalmucosarelaxant(tosecuremuscle
relaxationinsurgicalprocedurewithoutdeep
anesthesia).
2.Usedtocontrolconvulsionsofstrychnine
poisoningandoftetanus.
3.aftershocktreatment(inmentaldiseases)asit
reducesconvulsion
4.Thecompoundwasalsoatemplateforthe
developmentofothermusclerelaxants,e.g:
atracurium.

144. Opium
•Opium(RawOpium)isthelatexobtainedbyincisionfromtheunripe
capsulesofPapaversomniferum(Papaveraceae).
•OpiumBPisrequiredtocontainnotlessthan10%ofmorphineandnot
Jessthan2.0%ofcodeine.Thethebainecontentislimitedto3%.

145. Production of Opium
•The plant is an annual herb with large solitary flowers, either white
or pink in color
•The incisions are made in the afternoon with an instrument
bears narrow iron spikes which are drawn down the capsule to
produce several longitudinal cuts.
•The incision must not penetrate into the interior of the capsule or
latex will be lost.
•The latex, which is at first white, rapidly coagulates and turns
brown.
•Early in the morning of the day following the making of the
incisions the partly dried latex is scraped off.
•Each capsule is cut several times at intervals of 2 or 3 days.
•After collection the latex is placed in a tilted vessel so that the
dark fluid which is not required may drain off.
•By exposure to air the opium acquires a suitable consistency for
packing.

148. opiumconstituents
•Opium contain more than 40 alkaloids usually combined with a specific acid
(Meconicacid) or with other acids e.g. sulfuric and acetic acids.
•Opium alkaloids can be sub classified into 3 main groups with different basic
nuclei:
1.Phenanthrenealkaloids e.g. morphine , thebaineand codeine.
2.Benzylisoquinolinealkaloids e.g. papaverineand noscapine(narcotine).
3.Phenylethylaminealkaloids e.g. narceine

149. Morphine
Narceine

151. Alkaloids of opium:
Morphine:
•Is the most important of the opium alkaloids,
morphine .
•The molecule contains a phenolic and an alcoholic
hydroxyl group.
•Morphine was a used as a template for other
analgesic agents including pethidine, which is one of
the most widely used synthetic opiates.
Uses
•Morphine and its salts are classed as narcotic
analgesics they are strongly hypnotic.
•post operative analgesic for major operations, and
for cancer patients (terminal pain).

153. Adverse effect:
1.constipation
2.sedation
3.nausea and vomiting
4.respiratory depression
5.Miosis
6.anticholinergic effect: dry mouth , urinary
retension
7.tolorance: increase doses required to
maintaneanalgesia.
8.dependence : addiction, if used for a long
time

156. Imidazole Alkaloids
Name Pilocarpine
Botanical Name: Pilocarpus jaborandi
Family Rutaceae
Chemical
Constituents
The important alkaloids are
pilocarpine, isopilocarpine, pilosine
and
isopilosine.
Use 1. Pilocarpine directly stimulates
the muscarinic receptors in the eye,
causing constriction of the pupil.
2. It may be used for the treatment of
glaucoma.
3. It is administered orally to stimulate
salivary secretion

159. Steroidal Alkaloids
Name :Veratrum Viride
Botanical Name :Veratrum viride
Family Liliaceae
Chemical Constituents: It contains large
number of steroidal alkaloids of which
germidine &
germitrine & veratrosine are important
Use
1. It is used as an antihypertensive and
insecticides.
2. In small doses, they principally affect the
blood pressure without
changing the cardiac and respiratory rate.
3. It is also used as cardiac depressants and
sedatives. {Cardioinhibitory drugs depress
cardiac function by decreasing heart rate
(chronotropy), myocardial contractility
(inotropy), or both, which
decreases cardiac output and arterial pressure.}