Download Quinoline and Iso Quinoline alkaloids

QUINOLINE AND ISO QUINOLINE
ALKALOIDS
By
Noor Hisham Al-Atraqchi
MSc.pharmacognosy
QUINOLINE ALKALOIDS
QUINOLINE ALKALOIDS



•
•

Alkaloids containing quinoline as 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,
Cinchonine and Cinchonidine.
Cinchona alkaloids are present as salts with Quinic and
Cinchotannic acids
Cinchona bark:






o
Cinchona succirubra (Rubiaceae), and its varieties
and hybrids containing not less than 6.5% of total
alkaloids. 30-60% of which consists of quininetype alkaloids.
The amount of alkaloids present depend on :
the species,
environment of the tree,
age,
method of bark collection.
The former importance of cinchona
bark and its
alkaloids in the treatment of malaria has been
lessened by the introduction of synthetic drugs, but
it remains of great economic importance.
CONSTITUENTS OF CINCHONA BARKS


Cinchona bark contains quinoline alkaloids.
The principal alkaloids are the stereoisomers quinine
and quinidine and their respective demethoxy
derivatives, cinchonidine and cinchonine.
Both Quinine and Quinidine, Cinchonine and
Cinchonidine are Diastereoisomers.
 Each pair differs in the stereochemistry at C-8 and C-9.

HO
H3CO
HO
9
N
N
H
H
H3CO
N
Quinine
8
H
H
N
Quinidine
Uses:
•
Galenicals of cinchona have long been used as bitter tonics and
stomachics.
•
Before World War II, quinine was the drug of choice for the
treatment of malaria but became largely superseded by the
advent of synthetic antimalarials developed during that period.
•
It has, however, remained of importance in Third World
countries and has re-emerged as suitable for the treatment
of Plasmodium falciparum infections (falciparum malaria) in
the many areas where the organism is now resistant to
chloroquine and other antimalarials.
Quinine also has a use as a treatment for night cramps in the
elderly .
•
Uses:
•
•
Quinidine is employed for the prophylaxis of cardiac
arrhythmias and for the treatment of atrial fibrillation:
it also has antimalarial properties and like quinine is effective
against chloroquine-resistant organisms.
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
ISOQUINOLINE
ALKALOIDS
Isoquinoline alkaloids :
•
The isoquinoline structure 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.
IPECAC ALKALOIDS



dried root or rhizome of Cephaelis
ipecacuanha of the Rubiaceae family.
It should contain at least 2%
alkaloids.
Constituents: Ipecacuanha contains
the alkaloids :

emetine,

cephaeline ,

psychotrine,

psychotrine methylether
•
emetamine.
These are isoquinoline derivatives.
IPECACUANHA USES
1.
2.
3.



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.
Expectorant
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.
Psychotrine and its O-methyl ether are selective
inhibitors of human immunodeficiency virus and
their study could lead to the development of
therapeutically useful agents.
Curare alkaloids
Tubocurarine:
•
•
Has a bisbenzylisoqinoline structure.
It is obtained from the bark and stems of Chondrodendrum
tomentosum ( 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 .
Tubocurarine chloride
USES
Tubocurarine chloride is employed as:
1. A skeletal mucosa relaxant (to secure muscle
relaxation in surgical procedure without deep
anesthesia).
2. Used to control convulsions of strychnine poisoning
and of tetanus.
3. after shock treatment (in mental diseases) as it
reduces convulsion
4. The compound was also a template for the
development of other muscle relaxants ,e.g: atracurium.
OPIUM


Opium (Raw Opium) is the latex obtained by incision from the
unripe capsules of Papaver somniferum (Papaveraceae) .
Opium BP is required to contain not less than 10% of morphine
and not Jess than 2.0% of codeine. The thebaine content is
limited to 3%.
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.
OPIUM CONSTITUENTS
 Opium contain more than 40 alkaloids usually combined with a

specific acid (Meconic acid) 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.
Phenanthrene alkaloids e.g. morphine , thebaine and codeine.
2.
Benzylisoquinoline alkaloids e.g. papaverine and noscapine
(narcotine).
3.
Phenylethylamine alkaloids e.g. narceine
Morphine
Narceine
USES OF OPIUM




Opium and morphine are widely used to relieve pain and
are particularly valuable as hypnotics, as, unlike many
other hypnotics, they act mainly on the sensory nerve cells
of the cerebrum.
Both morphine and codeine decrease metabolism, and
the latter, particularly before the introduction of insulin,
was used for the treatment of diabetes.
Opium, while closely resembling morphine, exerts its
action more slowly and is therefore preferable in many
cases (e.g. in the treatment of diarrhoea).
Opium is also used as a diaphoretic.
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).
ADVERSE EFFECT:
1.
2.
3.
4.
5.
6.
7.
8.
constipation
sedation
nausea and vomiting
respiratory depression
Miosis
anticholinergic effect: dry mouth , urinary
retension
tolorance: increase doses required to maintane
analgesia.
dependence : addiction, if used for a long time
Codeine:
 Is the most widely used opium alkaloid obtained from opium or
prepared from morphine by methylation (of phenolic hydroxyl
group) or from thebaine reduction and demethylation, it is
methyl morphine (replace the phenolic hydroxyl group).
Uses
• Codeine and salt has narcotic analgesics
• Codeine mainly used as antitussive, it suppress the coughing
center in brain.
• Codeine is less toxic and much weaker in action than morphine
with less development of tolerance.
The habitual use of codeine may, in some individuals, produce
constipation
PAPAVERINE
-Benzyl isoquinoline type
An opiate alkaloid isolated from the plant Papaver somniferum and
produced synthetically.
Action and uses:
1-papaverine decrease the tone of smooth muscles. It has
spasmolytic and vasodilatation effect
2-it is neither narcotic nor addictive
NOSCAPINE
Noscapine or narcotine exists in opium as
free base (3-10 %), it posses
cough
suppressant properties.
Thebaine
Thebaine is the starting point for the
synthesis of many agents, including codeine
and veterinary sedatives such as etorphine.
SEMISYNTETIC PREARATION
HEROIN
Heroin: (diacetyl morphine).
 It is formed by acetylation of both hydroxyl
groups using acetic anhydride .
 Heroin’s action is similar to morphine but
more potent and dangerous of habit formation.
 This agent is highly useful in the management
of pain, particularly in patients with terminal
cancer.
