Transcript Isoquinoline Alkaloids

Isoquinoline alkaloids
1-Benzyl isoquinoline type: Papaverine: An opiate alkaloid isolated from the
plant Papaver somniferum and produced synthetically.
Pharmacology:
1-papaverine decrease the tone of smooth muscles. It has spasmolytic and
vasodilatation effect
2-it is neither narcotic nor addictive
3-it is of beneficial effect on angina pectoris
4-used for treatment of pulmonary embolism and cerebrovuscular
thrombosis.
2-benzyltetrahydroisoquinoline
Ipecac alkaloids:
Emetine, cephaline,
psychotrine : obtained
from the roots of Cephalis
ipecacuana, (family
Rubiaceae),it cause
vomiting and has local
reputation for use for
dysentery.
Mode of action : locally by
irritation of mucous
membrane of stomach and
intestine. These days its
use as emetic is less
because of this effect
Pharmacology:
1-for dysentry ( entamoeba histolitica ):
because of its emesis effect
2-for poisoning cases in hospitals
3-in small doses emetine and cephaline are
expectorant
4-ipecac extract used also as expectorant
3-Bis-benzyl isoquinoline : curare
alkaloids
Tubocurarine: obtaine from the bark
and stems of Chondrodendrum
tomentosum ( family
Menispermaceae)
from urari; The term curare is used
to indicate crude extract prepared
from different species and was used
by certain natives of the Amazon
regions of South America as arrow
poison. Some of these extracts were
poisonous by virtue of a convulsant
action and others by paralyzing
action.
The bark and stems of the plant are
extracted by boiling with water and
straining or by percolation with
water or alcohol. The extract is
concentrated to a standardized
concentration to be used
Pharmacology:
1-curare posses a paralyzing effect
on voluntary muscles, a toxic one on
blood vessels and histamine –like
effect. Most of the activity
attributed to d-tubocurarine
Uses
1-in surgical anaesthesia as it
produce muscular relaxation
without a deep anaesthesia.
2-after shock treatment (in mental
diseases) as it reduces convulsion
3-to control convulsion after
strychnine poisoning.
Tubucurarine
4-Opium is reported to contain •
many alkaloids (about 40), the
most important of them are :
Morphine, codeine, thebaine, •
papaverine, noscapine and
narceine. They are devided into 4
groups according into structures:
1-benzylisoquinoline: like •
papaverine
4-phenanthrene:e.g., morphine, •
codeine, thebaine
Opium is the dried milky •
exudates, or latex, obtained by
incising the unripe capsules of
opium poppy.
the plant is an annual herb with large
solitary flowers, either white or pink
in color. To obtain the latex by
incision of the ripening capsule , just
changing in color from blue-green to
yellow. The latex tubes opine one
into another. The incision made at
night , the milky exudates oozes out,
but rapidly turns brown and
coagulates , collected the next
morning by scrapping from the
capsule. the raw opium is moulded
into balls or blockes and wrapped in
poppy leaves and shade dried.
The plant cultivated for black market
in Asia minor, Afphganistan, also
Turkey, Burma, Laose and latin
America (Mexico and Colombia).
Official drug cultivated in China,
India.
•
•
Oppose: latex of op[ium •
Endogenous opiates: •
• Receptors for morphine and
codeine have been detected in
the brain. This resulted in
isolation of enkephalins ( metenkephalin, leo-enkephalin),
endorphins and dynorphins,
which are small peptides
produced marily but not
exclusively in the pituitary gland.
it is interesting that codeine and
morphine are present in
mammalian tissue, particularly in
brain tissue
Morphine
thebaine
Codeine
Pharmacology
The pharmacological action of opium
is due to morphine first which act as
stimulant first then sedative hypnotic
depressing the CNS.
Effect :
1-analgesia
2-miosis
3-euphoria
4-respiratory depression
5-sedation
6-physical dependence
7-bradycardia
8-constipation
Adverse effect:
1-constipation
2-sedation
3-nausea and vomiting
4-respiratory depression
5-dependence : addiction, if used
for a long time
6-anticholinergic effect: dry
mouth , urinary retension
7-CNS excitation
8-tolorance: increase doses
required to maintane analgesia
Withdrawal symptoms:
1-anxiety
2-irritability
3-insomnia
4-chills
5-salivation
6-diaphoresis
7-nausea 8-vomiting 9-GI cramping and diarrhea
These symptoms last for about 10-14 days , unless a further dose of
morphine is taken.
Uses:
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.
Uses :
Morphine : post operative
analgesic for major
operations, cancer patients
(terminal pain).
Semisynthetic preparations:
1-herion:
morphine diacetate, highly addictive
analgesic, with more lipophilicity.
resulted in much abuse of the drug.
•
3-pethidine:less potent than
morphine, with shorter duration of
action . used by addict people. Less
constipating
5-methadone:similar activity to
morphine with longer duration of
action and different withdrawal
symptoms, used in rehabilitation
program for addict patients.
6-tramadol: new analgesic drug ,act by 2
mechanism,morphine mechanism and
serotonine adrenergic pathway. Produce
typical morphine side effects.
4-fentanyl: 50-100 times more
analgesic effect than morphine.
Indole alkaloids
Ergot alkaloid
Ergot is the product of filamentous
fungus( dried sclerotium) of
Claviceps purpurea family
Hypocreaceae that grow parasitically
on rye and other graminaceous
plants.
-in the past ergot played a tragic role
as cause of a devastating epidemic
poisoning in Europe in the middle
ages, called Saint Antony fire (
Ergotism). The toxicity is manifested
in tow forms:
1-Ergotism:gangrene of the
exteremities which resulted in
bloodless, often dramatic , loss of
blackened limbs ( vasoconstriction)
2-Delerium and hallucination which
may lead to convulsions.
Ergometrine ( ergonovine) structure:
•
Production of ergot alkaloids:
achieved through the followings
1- Isolation from the crude drug
grown parasitically in the field (
parasitic cultivation) : this method
involves culturing in vivo of the
conidia suspension either by
spraying or more efficiently by
injection using for industrial scale
production inoculation machines to
infect large fields.
2-extraction from saprophytic
cultures ( artificial nutrient medium)
: in this commercial method the
mycelium of a selected strain is
allowed to grow in submerged
cultures producing lysergic acid
amide
3-partial and total synthesis
Ergot alkaloids are composed
of lysergic acid and its isomer
isolysergic acid, combined
through an amide linkage
with a peptide rest (
ergotamine group ) or with an
aminopropanol ( ergometrine
group ).
Lysergic acid ethyl amide ( LSD ):
LSD is a potent psychotic drug : it is thought to
act by interfering with normal serotonergic
transmission. The psychic effects are very
marked: perceptual changes ( shapes, sounds,
colors ) subjective time alteration , a
disintegration of the self, an increase in
suggustability.
Lysergic acid structure:
ergometrine
This alkaloid causes prompt and •
vigorous contraction of the uterus (
oxytocic action ), it is used for
prevention of hemorrhage after child
birth.
• It has a medical use in obstetrics to
facilitate delivery of the placenta and
to prevent bleeding after childbirth by
causing smooth muscle tissue in the
blood vessel walls to narrow, thereby
reducing blood flow. It is usually
combined with oxytocin (Syntocinon)
as syntometrine.
• It can induce spasm of the coronary
arteries.[2] It is used to diagnose
Variant (Prinzmetal's) angina.
Side effects[edit]
Possible side effects include nausea,
vomiting, abdominal pain, diarrhea,
headache, dizziness, tinnitus, chest
pain, palpitation, bradycardia,
transient hypertension and other
cardiac arrhythmias, dyspnea,
rashes, and shock.[4]
Mechanism of action
While it acts at alpha-adrenergic, dopaminergic, and serotonin
receptors (the 5-HT2 receptor), it exerts on the uterus (and
other smooth muscles) a powerful stimulant effect not clearly
associated with a specific receptor type.
The official salt is ergotamine tartaret , it is
unstable, specially in aqueous solution and
on exposure to light. On hydrogenation ,
dihydroergotamine is produced, which is
used as migraine analgesic ( cafergot tablets
with caffeine)
Applies to ergotamine: oral tablets, rectal
suppositories, sublingual tablets
Cardiovascular side effects have included
hypertension, tachycardia, bradycardia,
precordial distress
Musculoskeletal aches, pains, and cramps,
as well as general muscular weakness, have
been reported.
Nervous system side effects have included
drowsiness, paresthesias, headache,
peripheral neuropathy, vertigo, tremor
Ergotamine
3 Vinca rosea alkaloid.
vinicristine and vinblastine:
These are obtained from Catharanthus roseus
(vinca rossea)which is a Madagascar plant.
It was used in folklore medicine for diabetes in
Europe for centuries and had a reputation as
magic plant.
The alkaloids in this plant referred to as Vinca
alkaloids
A screening programme at the pharmaceutica
company Eli Lilly revealed that extracts
inhibited growth of certain types of cancer
cells.
Bioassay –guided isolation of extracts of the
plant led to the finding of these 2 alkaloids .
Problem with this plant that the content are
extremely low
Vincristine:The generic name for it is Oncovine
( Eli Lily)
Used for acute leukemia, Hodgkin”s
disease and other lymphomas.
Mode of action: inhibiting mitosis by
binding to tubulin prevent spindle s
formation.
Vinblastine: the other drug which is
used for Hodgkin “s disease,
lymphomas, advanced testicular and
breast cancer. The generic name Vilbe
vincrstine
3-strychnus
alkaloids:
The genous strychnus ( Loganaceae.
The Asian species are source of strychnine
and brucine , while the South American
species are the source of certain types of
curares.
Strychnos nux vomica L. and Strychnus
ignati seeds are known to contain the
principle alkaloids strychnine and brucine
( 2-3 %).
Mode of action : strychnine is CNS
stimulant with no inhibition at the post
synaptic level which may lead to
convulsion.
Uses
1-it has been used as a general tonic
, but this use is prohibited owing to
its marked toxicity.( lethal adult
dose is 60-90 mg)
2- it is of limited use in modern
medicine as a respiratory stimulant.
3-the greatest use of strychnine is in
the form of biscuits ( rat poison)
Brucine: the same effect as
strychnine with less CNS
stimulation. used as ethanol
denaturant
4-Rauwolfia alkaloids:
They occur in the roots of
Rauwolfiaserpintena, Apocynaceae.
The important alkaloids in this plant
are:
Reserpine , deserpidine, recinnamine
more than 40 alkaloids had been
isolated from different species of
Rauwolfia.
Ajmaline, ajmalicine serpentine
serpentinine, yohimbine
uses:
Reserpine leads to constant loss of
serotonine, norepinephrine and
dopamine from the nervous tissue. This
explain its sedative , tranquilizing and
hypotensive effects
5-Calabar bean alkaloids
Physostigmine(eserine): is the main
alkaloid in the seeds of Physostigma
venenosum, Leguminosae
Pharmacology and uses:
Physostigmine is a choline –esterase
inhibitor.
1-Used in the form of ointment
0.25% for treatment of glaucoma.
2-it stimulate the secretion of saliva
and perispiration and increase the
tone and peristalsis of the GI tract.