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Phytochemistry (2)
Lecture 21 :the last part ergot alkaloids
-semi-synthetic lysergic acid derivatives :
-lysergic acid diethylamide (LSD):
The most hallucinogenic drug ever , discovered by a man .
-when we talked about hallucinogenic drugs (morphine ,cocaine
,…) we call the dose in (mg) ,but her in LSD because it
considered very potent we call the dose in (µg).dose of LSD
usually (25 µg ) and the largest dose not exceed ( 100 µg )
-LSD works on alpha adrenergic , dopaminergic, serotonergic
receptors (agonist and antagonist at the same time ).
-it produces pronounced hallucinogenic effect , it affects all the
receptors in your mind .
-usually we call the dose of it (after taking the drug ) “trip”.
-trip could be one of two :
1-bad trip
2-pleasured trip
-the user could not expect where he/she is going ,it depends
mainly on his/her situation at the first time he/she took the drug.
-keep in mind : these two trips are not the same.
For example : in first day he/she take the drug and go for bad
trip , in the second day if he/she take the drug he/she will go
also to bad trip but totally different from the trip in the day
before
-it is characterized by what we call (flashback) (back in memory).
-usually he/she will go to very deep hallucinogenic trip (auditory
/visual hallucination).
-it ends usually by manic behavior and extremely dangerous
behavior , and after that he/she could not remember what he/she
did .
-in the slides there are stamps , they put the dose of LSD on it ,
because it is very small (not exceeds 100 µg),
And it also reflect user imagination during the using of LSD .
-we never classify the drug as addict drug unless it has :
1-physical dependence 2-psychological dependence
-here in LSD ,because the patient usually hate the drug
especially with bad trip and flash back, the psychological
dependence is less than the other hallucinogenic drugs .
-it can lead to schizophrenia .
-there is a high incidence of suicidal attempts .
-in certain rare cases , the effect of LSD could be irreversible (no
way to come back).
-LSD is not anymore used.
-it has not any medical application.
-it is prohibited internationally.
-there are many drugs in the market , marketed as LSD but it is
not LSD . one of them is (DMT) ‫ الفيل االزرق‬,it is totally synthetic
drug ,it is practically have some of the effect of LSD ,but it is not
LSD .
-maximum last of LSD is 12 hours ,after 12 hours the user
returns to his normal situation (usually).
*structure :
LSD structure
acetylcholine
structure
Dopamine
structure
Serotonin
structure
-LSD acts as dopaminergic and alpha adrenergic (all lysergic
acid ).
-if we take the whole drug with indole ring ,it is similar to
serotonin ,so it acts also as serotonergic .
2- anthranilic acid derived alkaloids :
- quinazoline structure.
-different plants which contains this type of compounds one of
them is :
Adhatoda Vasica
It is Indian plant , now it is available in the market .
Vasicine (peganine): the active constituent (quinazoline
derivative )
-it is used as bronchodilator and antitussive .
-example in the market : (zeal/zealcough)
3-Histidine derived alkaloids :
histidine
histamine
decarboxylation
-histidine contains imidazole ring.
-histamine is produced as anaphylactic (one of the anaphylactic
mediators in our bodies ).
-why people say :don’t eat fish with yogurt ?
Because fish contains histidine and all dairy products contain
histidine .so, most probably they will be converted into
histamine and cause allergic reaction (rash).
-histamine produced as defense mechanism such as seasonal
allergy .
-stress also stimulates histidine decarboxylase enzyme so ,more
production of histamine .
-in this case antihistamine drugs are sufficient ,the best is to use
it intranasal or locally .
-what is the relationship between histamine and asthma ??
Histamine cause bronchoconstriction ,so antihistamine
suppress the effect of histamine and relief (cough /shortness of
breath ,…)
-plants containing histidine :
Policarpus Jaborandi :
Pilocarpine : identical/similar pharmacological effect to that of
physostigmine .so it is a cholinergic drug ,but the mechanism of
action is different .
-it is usually used to treat glaucoma .
-in most eye drops we can find a compination of physostigmine
and pilocarbine .
-Physostigmine act as choline esterase inhibitor .
-pilocarpine works mainly on muscarinic receptors which found
in the eye , it stimulates the effect of acetylcholine .
-as it works by different mechanism of physostigmine ,usually
we find them together ,if we assume that they have the same
mechanism we can use one and increase its dose .
Structure :
Muscarine structure
acetylcholine structure
pilocarpine
structure
-muscarine is similar to acetylcholine by having quaternary
ammonium ,1-2carbon bridge ,and the ester or ether linkage .
-in the case of pilocarpine ,side chain is part of the
pharmacophore not just the imidazole ring .
-it also be used for the treatment of Alzheimer disease .
4-Amination reaction derived alkaloids :
There are 3 types :
1-true alkaloids
2-pseudo alkaloids
3-proto alkaloids :e.g :colchicine /no hetero cycle ,but it derived
from amino acid.
-but here in amination reaction alkaloids we will see something
different ,here not derived from amino acid but containing
nitrogen in heterocycle .
-terpenoid alkaloids
-steroidal alkaloids
*terpenoid alkaloids :contain terpene in its structure mainly
diterpene (4 isoprene units (20 carbon atom )) at the end the
nitrogens the structure .
*steroidal alkaloids: here we have steroidal nucleus (four fused
rings).
-we saw before the diosgenin which used as a precursor for the
synthesis of steroids .
-if we replace the oxygen in the structure of diosgenin by
nitrogen atom , it will be steroidal alkaloids.
Steroidal alkaloids
structure
-aconitine (aconite (a.c )) ‫خانق الذئب‬
-highly toxic plant ,it is aneurotoxin ,act on all sodium channels
of our bodies .
-it has no medicinal use .
-structure is very difficult.
-they tried to modify it ,but because of its high neurotoxicity they
failed.
-steroidal alkaloids :the green part in the potato fruit and green
tomato usually contain this type of alkaloids.
**structure (please refer to slides )
Here we have steroidal nucleus , in the side chain we have
nitrogen atom ,so its steroidal alkaloids (OH at position 3 have
sugar moiety ) .
-all of these compounds (steroidal alkaloids ) are regarded as
toxic compounds (not fetal as aconite).
-green potato ,tomato will cause abdominal upset ,it may cause
vomiting , diarrhea.
-usually all of these compounds are found in leaves of this plant,
because of this we don’t eat this leaves.
-in fruits ,if there are immature fruits (green) ,so it will produce
toxic effect.
-they have pharmaceutical important ,because they are
precursor for steroidal synthesis (like diosgenin).
-all alkaloids especially steroidal alkaloids found in solanaceae
family ‫الفصيلة الباذنجانية‬
-important question :
‫في حالة مخلل البندورة الزم تكون البندورة خضراء كيف ما بيصير عندي تسمم ؟؟‬
-we prepare the tomato pickles by adding (acetic acid)the
addition of acetic acid will convert the steroidal alkaloids into
salt , so it will dissolve in the water .
-eggplant ‫ الباذنجان‬: there is a steroidal alkaloids especially in the
leaves .
Good luck :)
https://www.youtube.com/watch?v=8ZIZtiWhnM8
this is the link for the video of the effects of LSD .