Bilad Alrafidain University College

Department of pharmacy

3rd stage/ 2nd coarse

Quinolizidine alkaloids
Alkaloidal amines
Purine alkaloids
Pharmacognosy-Lecture 5
Assistant Lecturer Marwan I. Al-Zuhairi / M.Sc.
Quinolizidine-Lupinane alkaloids
• Lupinane contains a methyl group at the quinolizidine
ring.
• These alkaloids of this group are found in scoparius
(broom tops) of cytisus scoparius .
• The alkaloids of this group are Lupinine, and Sparteine
and they are known to be toxic alkaloids.
• Those are biosynthesized by 2 lysine molecules.
• Sparteine is the most important alkaloid, it’s a bitter
viscous liquid alkaloid it can be used to induce uterine
muscles due to its oxytocic action.
• The usual dose to induce labor is 75 mg IM.
 Alkaloidal amines
Proto-Alkaloids (Atypical alkaloids)

• The alkaloids in this group do not contain heterocyclic nitrogen atoms, the nitrogen
is not a part of the heterocyclic ring, so it is called atypical alkaloids.
• Many are simple derivatives of phenylalanine & tyrosine; Other alkaloidal amines
are biosynthesized from tryptophan.
• Drugs containing alkaloidal amines:
1) Ephedra which contains Ephedrine
2) Colchicum which contains Colchicine.
3) Khat which contains Cathinone. ( Leaves)
4) Peyote which contains Mescaline. (Tops)
 1. Ephedra:
• It is the entire plant or the over ground portion of Ephedra sinica F:
Gentaceae.
• The main alkaloids isolated from the various Ephedra species are
Ephedrine & Pseudoephedrine which are stereo-isomers.
• Ephedrine exhibits optical isomerism since it has two chiral centers,
giving rise to four stereoisomers.
• The pair of enantiomers with the stereochemistry (1R,2S) and
(1S,2R) is designated ephedrine, while the pair of enantiomers with
the stereochemistry (1R,2R) and (1S,2S) is called pseudoephedrine
• Pseudoephedrine can be formed by boiling Ephedrine with 25% HCL.
 Production of Ephedrine
• Natural: Ephedrine is produced commercially either by extraction of plant
material or by chemical procedure.

• Synthetic: It could be synthesized from phenyl ethyl ketone in the presence of

methyl amine.

• Semisynthetic :It also could be produced by fermentation of sugar in the presence

of benzaldehyde & methyl amine as shown below:
Uses:
• Ephedrine is an Adrenergic compound used as bronchodilator in asthma ; It is a potent
sympathomimetic.
• It works mainly by increasing the activity of nor epinephrine (nor adrenaline) on
adrenergic receptors, having longer duration of action than NE.
• It excites the sympathetic nervous system causes, vasoconstriction, cardiac stimulation
& rise in blood pressure (prevent low blood pressure during anesthesia).
• It is most usually marketed as the hydrochloride or sulfate salt. It is commonly used as a
bronchodilator in asthma and hay fever, it also acts as a stimulant, decongestant, and
appetite suppressant.
• 0.5-1% solution of ephedrine is used as a nasal decongestant
• Pseudoephedrine has similar actions with less potency.
• Biosynthetic precursor is phenylalanine by shikimic acid pathway.
 2. Colchicum:

• From the seeds and corm of the plant Colchicum autumnal F: Liliaceae.
• Colchicum contains the alkaloid Colchicine up to 0.8% in the seeds &
0.6% the corm.
• The biosynthesis precursor is phenylalanine in addition to tyrosine.
• The tropolone ring is formed by inclusion of a carbonyl group in the
six-member ring.
• Colchicine lacks basicity and does not form a well-defined series of
salts as do other alkaloids.
• It is used in gout to increase the excretion of uric acid.
• It also causes doubling of chromosomes prevents formation of
microtubules affecting mitosis thus, causing certain mutations in some
types of tumors., experiments show that injection of colchicine will
Inhibit the growth of certain tumors.
 3. Khat:
• It is the fresh leaves of Catha edulis F: Celastraceae. The plant is a small
tree or shrub.
• It is cultivated extensively in the Ethiopian highlands (Africa) and in
Yemen, Fresh leaves are regularly transported by air to areas distant
from the centers of cultivation.
• The Expert Committee of Addiction-producing Drugs of the WHO does
not classify khat as a to cause serious addiction however , it is
considered as a drug of abuse that can cause psychological dependence.,
but the French government considers it as an addictive drug.
• The leaves are chewed habitually by many people to alleviate the
sensation of hunger & fatigue which is like that of coca leaves causing
the stimulatory effect of cocaine. Cathinone
• Khat contains a potent phenyl alkyl amine alkaloid called (-)-cathinone.
It has pharmacological properties analogous to those of (+)-
amphetamine with similar potency and mechanism of action by the
induction of catecholamine release from the storage sites.
• Cathinone is stimulant that causes excitement , loss of appetite and
euphoria. Amphetamine
 Fresh vs. Dry khat leaves
• The young fresh leaves that come from the tips of the
branches contain the optimum mount of cathinone. In older
leaves, it is converted to the weakly active compounds
cathine which has weaker activity.

Cathinone Cathine
 4. Peyote:
• It consists of the dried tops of Lophophora williamsii F: Cactaceae. This plant has
been associated with Indian ceremonies for many years.
• Peyote main action to disturb normal mental function & causes concomitant
hallucination & euphoria.
• The drug contains several alkaloids, the most important one is mescaline,
• Mescaline (3,4,5-trimethoxy phenylethylamine) is regarded as the first of a series
of hallucinogens or psychotomimetic.
 Purine bases
Pseudoalkaloids
• Pseudoalkaloids have nitrogen in a heterocyclic ring however not derived from an
amino acid.
• The purines are derivatives of a heterocyclic nucleus consisting of the 6-membered
pyrimidine ring fused to the 5-membered imidazole ring.
• The pharmaceutically important bases of this group are the methylated derivatives
of 2,6-dioxypurine (Xanthine: di-keto purine)

Xanthine
Purine
 Purine bases

• Caffeine is 1,3,7-trimethyl xanthine

• Theophylline is 1,3-dimethyl xanthine
• Theobromine is 3,7- dimethyl xanthine
Plants containing
purine bases

• Cola (Kola)
• Coffee
• Tea
• Cacao
 Uses of purine bases:

• Caffeine: (prescribed by cardiologists, pediatrics and many physicians)

• Stimulant and a diuretic
• Caffeine is used to treat intermittent pauses in breathing (apnea) in premature
infants .
• prescribed pain relievers (such as acetaminophen) can decrease acute pain from
certain conditions, such as migraines.
• Theophylline is a smooth muscles relaxant, for symptomatic relief and
prevention of bronchial asthma also as diuretic.
• Theobromine: It has a stronger diuretic effect than caffeine however, It has
little stimulant action on the, CNS also it is preferred over caffeine in treatment of
cardiac edema and angina pectoris.
 Mechanism of action of caffeine:
Adenosine antagonism

• As it is both fat and water-soluble, it readily crosses the

blood-brain barrier, resulting in antagonism enhancing
wakefulness.
• Adenosine receptors are not limited to the CNS but are
present throughout the body. In cardiac muscle, direct
antagonism of receptor results in positive inotropic effects.
• Furthermore, adenosine receptor blockage stimulates
respiratory drive and improving diaphragm contractility.
• Caffeine increases renal blood flow, glomerular filtration,
and sodium excretion resulting in diuresis.
 1.Cola, Kola, or kolanuts:
• It is the dried seeds of Cola nitida F: Sterculaceae.
• Kola nuts contain Caffeine up to 3.5% & Theobromine less than 1%.
• Kola nut is important because of its caffeine content & its flavor.
• Its principle use in USA is in the manufacture, of non- alcoholic
beverages.
• In the fresh nuts, these purine derivatives are bound to the tannins
(catechin condensed tannin: kola catechin), during the drying process,
the complex is split, yielding free caffeine & theobromine &
converting the colorless kola catechin to the red-brown kola-red due
to the polymerization of tannins forming phlobaphene.
• Uses: Kola possesses the central stimulant action of caffeine. It is an
ingredient in several carbonated beverages.
2. Coffee beans :
• It is the dried ripe seeds of Coffee Arabica F: Rubiaceae, deprived from most of
the seeds coat.
• Coffee seeds contain from 1-2% of caffeine, 3-5% tannins, &3-5% proteins.
 Coffee
• The aroma of coffee is caused by oil known as caffeol,consisting of about 50% furfural with
traces of valerianic acid, phenol & pyridine. It is produced during the roasting process.
• At the same time, the caffeine is freed from its combination with chlorogenic acid with which
it exists in the unroasted seeds.
• The caffeine may be partially sublimed during this roasting process; much of the caffeine of
commerce is collected in condensers attached to coffee roasters.
• The action of coffee depends principally on the caffeine contents which act on the CNS,
kidney, muscles & heart.
• Decaffeinated coffee, is prepared by extracting most of the caffeine from coffee beans yet
retaining the pleasant characteristic aroma of coffee. Such preparation normally contains up to
0.08% of caffeine.
 3. Tea (Thea)
• It is the dried leaves & leaf buds of Camellia sinensis F: Theacea.
• Tea contains 1-4% caffeine, theophylline, theobromine, xanthine
and gallo-tanic acid.
• The stimulating action of tea is due to caffeine; its astringent
properties are owing to the tannin's contents.
• Green tea is prepared in China & Japan by rapidly drying the
freshly dried leaves in copper pans over a mild artificial heat.
• Black tea is prepared in SriLanka and India by heaping the fresh
leaves until fermentation has begun then they are rapidly dried
artificially with heat.
 4. Cocoa seed

• Theobromine: It is a compound prepared from the dried ripe

seeds of Theobroma cacao F: Sterculiaceae.
• It contains mostly Theobromine and less amounts of caffeine.
• It is used as diuretic & smooth muscles relaxant.
• It has a stronger diuretic effect than caffeine however, It has little
stimulant action on the, CNS & so it is preferred over caffeine in
treatment of cardiac edema and angina pectoris.
 Caffeine content in beverages

THE END