part1 of Alkaloids report, History up to Quinolines Alkaloids

1. ALKALOIDS

2. 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

3. 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.

4. STRUCTURE OF ALKALOIDS

5. 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.

6.  Most but not all alkaloids possess basic
properties owing to the presence of
amino nitrogen.
 Structurally complex end products of
energy- requiring reaction sequences.

7.  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.

8. 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.

9.  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)

10.  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

11. 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.

12.  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

13.  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.

14.  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).

15. 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.

16.  For regulatory growth factors
 Reserve substance capable of supplying
nitrogen or other elements necessary to
the plant’s economy

17. 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)

18. BIOSYNTHESIS OF ALKALOIDS

19.  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, a
nthranilic acid, lysine and ornithine.

20.  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.

21. 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]

22. 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]

23. 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

24. 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)

25.  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)

26. CLASSIFICATION OF ALKALOIDS
 Pyridine- Piperidine Combined
 Tropane
 Quinoline
 Isoquinoline
 Indole
 Imidazole
 Steroid
 Alkaloidal amine
 Purine

27. PYRIDINE- PIPERIDINE COMBINED
 Also referred to as Pyrrolizidine alkaloids
 Upon reduction, the tertiary base, pyridine, is
converted into the secondary
base, piperidine.

28. 3 Subgroups
 Derivatives of piperidine
 Derivatives of nicotinic acid
 Derivatives of both pyridine and pyrrolidine

29. Important alkaloidal drugs and alkaloids that are
classified in this group are:
 Areca
 Arecoline
 Hydrobromide
 Lobelia
 Lobeline
 Nicotine

30. 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.

31.  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

32.  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.

33. 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.

34. ARECA
 Areca nut or Betel
Nut
 A dried, ripe seed of
Areca catechu (Fam.
Palmae)
 Areca- a Spanish and
Portuguese term for
betel nut

35.  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.

36. Uses:
 Pharmaceutic purposes
 Anthelmintic or vermicide in veterinary
practice
 Taenifuge

37. 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)

38. 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

39.  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

40.  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

41. 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.

42. 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.

43. Important alkaloidal drugs and alkaloids that
are classified in this group are:
 Belladonna leaf
 Hyoscyamus
 Stramonium
 Atropine
 Hyoscyamine
 Scopolamine
 Coca
 Cocaine

44. 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)

45.  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

46.  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)

47. Constituents:
 (-)- hyoscyamine
 remainder atropine
 Apoatropine
 Belladonnine
 Cuscohygrine
 Scopolamine

48. SOLANACEOUS ALKALOIDS
The principal alkaloids of this group are:
 (-) hyoscyamine
 atropine [(±) – hyoscyamine]
 scopolamine (also known as hyoscine)

49. 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

50. Atropine
 An antidote in case of poisoning caused by
cholinesterase inhibitors.
 It is a CNS stimulant.

51. 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.

52. 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

53. 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.

54.  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.

55. 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.

56. 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

57. 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

58. 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.

59.  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.

60. HYOSCYAMUS

61. 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)

62.  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

63. STRAMONIUM SEED
 from D. stramonium
 The seed contains
0.4% of
alkaloids, principally
hyoscyamine with a
small portion of
scopolamine and
traces of atropine.

64.  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

65. 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)

66.  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

67. Huanuco coca
 Contains 0.5 to 1% of ester
alkaloids, derivatives of tropine and
ecgonine
 Cuscohygrine is the principal nonester
alkaloid in the leaf.

68. 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”

69. 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

70. Crack
 extremely addictive smokable forms of
cocaine processed from cocaine
hydrochloride
 Its name refers to the sound made when
rocks of cocaine are smoked.

71. 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.

72. CINCHONA BARK

73.  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)

74.  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)

75.  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.

76. 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.

77. 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.

78.  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 .

79.  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.

80. 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.

81. Quinidine gluconate
 It occurs as a white powder odorless and has
a bitter taste available in sustained release
tablet.

82. 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

83. 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.

84. 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.

85. 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.