Download Indole alkaloids

Indole alkaloids
Pharmacognosy III
Mosul University/ college of Pharmacy
By: Noor Hisham Al Atraqchi
Indole alkaloids :
Numbers of important alkaloids posses an indole ring as part of
their structure.
The important drugs and their alkaloids of the indole group are:
• Rauwolfia
reserpine
• Nuxvomica
strychnine and brucine
• Physostigma
physostigmine
• Catharanthus (Vinca)
vinblastine and vincristine
• Ergot
ergotamine and ergomatrine
Rauwolfia serpentine
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Rauwolfia consists of the dried rhizome and roots of
Rauwolfia serpentiana. (Apocynaceae), a small shrub
found in India, Pakistan, Burma and Thailand
Constituents
Rauwolfia contains at least 30 alkaloids which total
some 0.7-2.4% , e.g.:
o ajmaline ,(rauwolfine)
o ajmalinine
o ajmalicin
o serpentine
o serpentinine
o The chief therapeutically important alkaloids are
reserpine.
 Other substances present include phytosterols,
fatty acids, unsaturated alcohols and sugars.
Uses
 Rauwolfla preparations and reserpine used in the management of
essential hypertension and in certain neuropsychiatric disolders.
 Ajmaline. which has pharmacological properties similar to those of
quinidine.is marketed in Japan for the treatment of cardiac arrhythmias
 Ajmalacine is mostly used as antihypertensive and anti-ischemic agent
(both central and peripheral). It has a broad application in the relief of
obstruction of normal cerebral blood flow.
Catharanthus Or Vinca
• is the dried whole plant of catharanthus roseus. 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 (dimeric indole) natural products present
in small quantities in the plant material.
•
Actions and uses
 Vincristine and vinblastine are mitotic inhibitors, arrest cell division at
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metaphase.
They act by binding to the protein tubulin in the mitotic spindle,
preventing polymerization and assembly into microtubule, thus stopping
the cell from separating its chromosomes during the metaphase; the cell
then undergoes apoptosis.
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
leukaemia in 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
OH
N
CH2CH3
.H2SO4
N
H
COOCH3
N
CH2CH3
H
H3CO
N H
HO
R
COOCH3
COOCH3
R= CH3 Vinblastine sulfate
R= CHO Vincristine sulfate
Nux vomica
 Dried ripe seed of strychnus nux vomica F. Loganiaceae.
 Nux vomica usually contains about 1.8-5.3% of the indole
alkaloids strychnine and brucine.
 Strychnine is physiologically much more active than brucine and
the seed are therefore assayed for strychnine and not for total
alkaloids .
 They usually contain about 1.23% of strychnine and about
1.55% of brucine.
Uses
• The action of the whole drug closely resembles that of strychnine. The
alkaloid was formerly used as a circulatory stimulant in such cases as
surgical shock, but its use is now more limited to that of a respiratory
stimulant in certain cases of poisoning.
• Like other bitters, strychnine improves the appetite and digestion, but it
has been considerably misused as a general tonic.
• Brucine: Is less toxic than strychnine and used commercially as an alcohol
denaturant
Calabar beans Is dried ripe seed of physostigma venenosum (F. leguminosae) ‘
Constituents :
Contain several alkaloids :
 Physostigmine (eserine),
 eseramine,
 geneserine.
 Isophysostigmine
 physovenine,
 Norphysostigmine
 Calabatine and calabacine
 The structure of geneserine, long regarded as an N-oxide, has
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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 sulphate and
is non-deliquescent.
Actions and uses of Physostigmine or
eserine:
 It reversibly inhibits AChE
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(choline esterase) and
enhance the effect of endogenous acetyl choline.
Physostigmine salicylate is used for contracting the pupil
of the eye, often to combat the effect of mydriatics
Physostigmine is used in the treatment of overdoses of
drugs with anticholinergic actions, such as atropine.
It has also been investigated as an intravenous injection
for reversing the effects of a number of sedatives.
For Alzheimer's disease : it has shown some evidence of
inducing a slight improvement in intellectual and
cognitive performance.
Ergot alkaloids
 Ergot (Ergot of
Rye) is the dried sclerotium of a fungus,
Claviceps purpurea (Clavicipitaceae), arising in the ovary of the
rye, Secale cereale. Controlled field cultivation on rye is the
main source of the crude drug.
Constituents of Ergot
 Cultivated ergot may contain up to 0.5% of total alkaloids, and
0.15% is a minimum commercial value.
 The ergot alkaloids (ergolines) can be divided into two classes:
(1) the clavine type alkaloids, which are derivatives of
dimethylergoline .
(1)
6,8-
the lysergic acid derivatives. which are peptide alkaloids. It is the latter
class that contains the pharmacologically active alkaloids that
characterize the ergot sclerotium
 Six pairs of alkaloids predominate in the sclerotium and fall into either
the water-soluble ergometrine (or ergonovine) group or the waterinsoluble ergotamine and 'ergotoxine' groups.
Uses
 Although whole ergot preparations were traditionally used in
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labour to assist delivery and to reduce post-partum hemorrhage,
ergot itself has been largely replaced in the pharmacopoeias by the
isolated alkaloids.
Only ergometrine produces an oxytocic effect ergotoxine and
ergotamine having quite a different action.
Ergometrine is soluble in water or in dilute alcohol. It is often
known, particularly in the USA, as ergonovine
Ergotamine and the semisynthetic dihydroergotamines salts are
employed as specific analgesics for the treatment of migraine.
Drug in pharmacy: ergotamine and used with caffeine for
treatment of migraine headache both act as cerebral
vasoconstrictors.
Lysergic acid diethylamide (LSD-25), prepared by partial synthesis
from lysergic acid, is a potent specific psychotomimetic, cause
CNS stimulation and it is drug of abuse .