Tikrit university

College of pharmacy
Pharmacognosy III 4th lec.

Indole Alkaloids

Indole alkaloids are a class of alkaloids containing a structural moiety of

indole; many indole alkaloids also include isoprene groups and are thus
called terpene indole or secologanin tryptamine alkaloids. Containing more
than 4100 known different compounds, it is one of the largest classes of
alkaloids. Many of them possess significant physiological activity and some
of them are used in medicine. The amino acid tryptophan is the biochemical
precursor of indole alkaloids.

two types of indole alkaloids are distinguished; isoprenoids and non-

isoprenoids

non-isoprenoids:
simple indole derivatives

One of the simplest and yet widespread indole derivatives are the biogenic
amines tryptamine and 5-hydroxytryptamine (serotonin). Although their
assignment to the alkaloid is not universally accepted, they are both found in
plants and animals.The tryptamine skeleton is part of the vast majority of
indole alkaloids.For example, N,N-dimethyltryptamine (DMT), psilocin and
its phosphorylated psilocybin are the simplest derivatives of tryptamine.
The three alkaloids, namely: serotonin, psilocin and psilocybin shall be
discussed in the sections that follow:

Serotonin

Synonyms 5-Hydroxytryptamine; 5-HT; Enteramine; Thrombocytin;

Thrombotonin;

Biological Sources The root bark of Gossypium hirsutum L. (Malvaceae)

(American Unplanted Cotton) contains serotonin.

Uses

1. It is a potent vasoconstrictor.

2. It is also a neurotransmitter in the CNS and is important in sleep-walking-

cycles.

Psilocin

Synonyms Psilocyn.

Biological Sources It is obtained from the sacred mushroom of Mexico

known as Teonanacatl. It is also found in the fruiting bodies of Psilocybe
maxicana Heim

Uses It is a hallucinogenic substance

Simple derivatives of β-carboline

The prevalence of β-carboline alkaloids is associated with the ease of

forming the β-carboline core from tryptamine in the intramolecular Mannich
reaction. Simple (non-isoprenoid) β-carboline derivatives include harmine,
harmaline, harmane and a slightly more complex structure of canthinone.

The alkaloids are derived from Peganum harmala (Syrian rue,

Zygophyllaceae), a plant used as an emmenagogue and alimentary tract
medicine, which is also known to evoke hallucinations. However, recently
their antiparasitic, antitumor, and antiviral properties are of greater interest
compared to their defined CNS activity.

Pyrolo-indole alkaloids

Pyrolo-indole alkaloids form a relatively small group of tryptamine

derivatives.A typical representative of this group is physostigmine.

Calabar bean and physostigmine

Calabar beans (Ordeal beans) are the dried ripe seeds of Physostigma
venenosum (Leguminosae), a perennial woody climber found on the banks
of streams in West Africa.

Constituents. The seeds contain the alkaloids physostigmine or

eserine,eseramine, isophysostigmine, physovenine, geneserine, N-8-
norphysostigmine, calabatine and calabacine.
Uses. Physostigmine salicylate is used for contracting the pupil of the eye,
often to combat the effect of mydriatics. It has also been investigated as an
intravenous injection for reversing the effects of a number of sedatives.
With Alzheimer’s disease it has shown some evidence of inducing a slight
improvement in intellectual and cognitive performance.

Isoprenoid indole alkaloids

Isoprenoid indole alkaloids include residues of tryptophan or tryptamine and
isoprenoid building blocks derived from the dimethylallyl pyrophosphate
and isopentenyl pyrophosphate.

A-Ergot and Ergot Alkaloids

Ergot (Ergot of Rye) is the dried sclerotium of a fungus, Claviceps purpurea

Tulasne (Clavicipitaceae), arising in the ovary of the rye, Secale ,
Interestingly, the poisonous properties of ergots in grain, specifically rye,
for animal as well as human consumption, purposefully and unknowingly,
have long been recognized. The dreadful causative agents are collectively
termed as the ‘ergot alkaloids’, containing essentially
an indole nucleus. These, group of alkaloids are also referred to
as ‘ergolines’.The three important and typical members of the ergot
alkaloids (ergolines), namely: ergonovine, ergotamine and lysergamde
(ergine) shall be discussed individually in the sections that follows:
Ergonovine

Uses

1. Ergonovine is used as an oxytocic.

2. Ergonovine maleate also acts as an oxytocic and produces much faster

stimulation of the uterine muscles as compared to other ergot alkaloids.

3. Methylergonovine meleate is observed to act as an oxytocic whose

actions are slightly more active and longer acting than ergonovine.

Ergotamine

Uses

1. It is employed as a potent antimigraine drug.

2. Ergotamine possesses oxytocic properties, but it is not employed for that

effect.

3. Ergotamine tartrate is used invariably to prevent or abort vascular

headaches, including migraine and cluster headaches. The mechanism of
action is perhaps due to direct vasoconstriction of the dilated carotid artery
bed with concomitant lowering in the amplitude of pulsations.

B- Monoterpenoid Indoles Alkaloids

Despite the considerable structural diversity, most of monoterpenoid indole
alkaloids is found in Alstonia, Rauvolfia and Catharanthus,Corynanthe ,
Strychnos

Nux vomica

Nux vomica consists of the dried, ripe seeds of Strychnos nux-vomica

(Loganiaceae), a tree 10–13 m high

Constituents. 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 seeds 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’. Nux vomica is used in Chinese medicine for much the
same purposes as in Western medicine and the seeds are usually processed
to reduce their toxicity. Heat-treatment of the seeds reduces the normal
levels of the principal alkaloids and the amounts of isostrychnine,
isobrucine, strychnine N-oxide and brucine N-oxide are increased.

Rauwolfia (Rauvolfia)

Rauwolfia consists of the dried rhizome and roots of Rauwolfia serpentina

(Rauvolfia serpentina), Apocynaceae, a small shrub found in India,
Pakistan, Burma, Thailand and Java. The geographical source appears to
influence the alkaloidal content, and manufacturers tend to prefer drug
obtained from India or Pakistan. Reserpine, the most important constituent,
is contained in many other species of Rauwolfia
Constituents. Rauwolfia contains at least 40 alkaloids, which total some
0.7–2.4%. In 1931 Siddiqui and Siddiqui isolated ajmaline (rauwolfine),
ajmalinine, ajmalicine, serpentine and serpentinine. The chief
therapeutically important alkaloids are reserpine and rescinnamine .

Uses. Rauwolfia preparations and reserpine are used in the management of

essential hypertension and in certain neuropsychiatric disorders. Ajmaline,
which has pharmacological properties similar to those of quinidine, is
marketed in Japan for the treatment of cardiac arrhythmias.An estimated
3500 kg of ajmalicine is isolated annually from either Rauwolfia or
Catharanthus spp. by pharmaceutical industries for the treatment of
circulatory diseases.

Conflicting reports on the possible involvement of the rauwolfia alkaloids in

breast cancer engendered a natural hesitation in their use. A report in the
Lancet (1976) suggested that the alkaloids do not initiate the carcinogenic
process but that they promote breast cancer from previously initiated cells

Yohimbe bark

Yohimbe bark is derived from Pausinystalia yohimbe (Rubiaceae), a tree

growing in the Cameroon Republic. It contains the indole alkaloid
yohimbine, which is
structurally related to reserpine.The bark is well-recognized for its
aphrodisiac property and yohimbine is effective in the symptomatic
treatment of erectile dysfunction.

Uncaria species

U. sinensis, have sedative and antispasmodic properties. They are used in

Chinese medicine for the relief of headaches and dizziness caused by
hypertension and for the treatment of convulsions in children.

U. tomentosa, one of two species found in S. America, features in the

traditional medicine of Peru. It produces similar hooks to U. sinensis being
known locally by the Spanish as ‘una degato’ (tomcat’s claw).

In a number of reports on this species, M. Kitajima et al., have recorded a

new glucoindole akaloid, 3,4-dehydro-5-carboxystrictosodine, various
triterpenes including nor-triterpene glycosides and cincholic acid glycosides
,The plant has a potential immunostimulant action and has been examined
for its pharmacological and toxicological properties
Catharanthus Roseus

The Madagascan periwinkle, Catharanthus roseus, has been variously

designated Vinca rosea and Lochnera rosea (Apocynaceae). It is indigenous
to Madagascar but is now widely distributed throughout warm regions and
is much cultivated as an ornamental; it grows profusely in southern Florida.
Commercial supplies of the drug are obtained from both wild and cultivated
plants produced in various locations, including Africa, India, Thailand,
Taiwan, eastern Europe, Spain, USA and Australia

Constituents. About 150 alkaloids have now been isolated from C. roseus;
some, for example, ajmalicine, lochnerine, serpentine and
tetrahydroalstonine, occur in other genera of the family. Of particular
interest is a group of about 20 bisindole alkaloids which contains those
having antineoplastic activity, including leurocristine (vincristine) and
vincaleukoblastine (vinblastine). Vinblastine is produced by coupling of the
indole alkaloids catharanthine and vindoline, both of which occur free in the
plant. Formation of 3′,4′-anhydrovinblastine from these monomers has been
effected with peroxidase isozymes isolated from C. roseus suspension
cultures and with commercial horseradish peroxidase (see J. P. Kutney, Nat.
Prod. Rep., 1990, 7, 85–103). Vincristine is structurally similar to
vinblastine, but has a formyl group rather than a methyl on the indole
nitrogen in the vindoline-derived portion. Because these alkaloids are only
minor constituents of the plant (vincristine is obtained in about 0.0002%
yield from the crude drug), large quantities of raw material are required and
chromatographic fractionations are extensively employed in the isolation
procedures. In addition, there is a growing demand for vincristine rather
than vinblastine, but the plant
produces a much higher proportion of vinblastine. Fortunately, it is now
possible to convert vinblastine into vincristine either chemically, or via a
microbiological N-demethylation using Streptomyces albogriseolus.

Uses. 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
cancers. The semi-synthetic vindesine is also used in the treatment of acute
lymphoid leukaemia in children.

Vincristine has a superior antitumour activity compared to vinblastine, but is

more neurotoxic. Vinorelbine is a newer, orally active, semi-synthetic
anhydro derivative of 8′-norvinblastine with a broader anticancer activity
and lower neurotoxic side-effects than the other Catharanthus alkaloids.

Vinca major and V. minor

The greater periwinkle (Vinca major) together with the lesser periwinkle (V.
minor) are the only members of the essentially tropical and subtropical
family Apocynaceae Vincamine, first isolated from V. minor in 1953, is
available as a vasodilatory drug.
The purines are derivatives of a heterocyclic nucleus consisting of the 6-membered
pyrimidine ring fused to the 5-membered imidazole ring. Purine itself does not occur in
nature, but numerous derivatives are biologically significant. The pharmaceutically
important bases of this group are the methylated derivatives of 2,6-dioxypurine
(xanthine) i.e. xanthine is diketo purine.

Xanthine

Caffeine is 1,3,7-trimethyl xanthine

Theophylline is 1,3-dimethyl xanthine
Theobromine is 3,7-dimethyl xanthine
Drugs containing purine bases
-Cola (Kola)
-Coffee
-Tea
-Cacao

1. Cola, Kola, or kolanuts:

It is the dried cotyledon of Cola nitida F: Sterculaceae.
It yields not less than 1% of anhydrous caffeine. Kola nut is important because of its
caffeine content & its flavor. Its principle use in USA is in the manufacture of non-
alcoholic beverages.

Kola nuts contain caffeine up to 3.5% & theobromine less than 1%. In the fresh nuts,
these purine derivatives are bound to the tannin, kolacatechin, during the drying
process, the complex is split, yielding free caffeine & theobromine & converting the
colorless kolacatechin to the red-brown kola-red.

Uses: Kola possesses the central stimulant action of caffeine. It is an ingredient in

several carbonated beverages.

Image of kola nuts

2. Coffee beans or coffee seeds:

It is the dried ripe seeds of Coffee Arabica F: Rubiaceae, deprived from most of the
seeds coat.

Roasted coffee is coffee roasted until it acquires a dark brown color & develops the
characteristic aroma. Coffee seeds contain from 1-2% of caffeine, 3-5% tannins, & 3-
5% proteins.
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.

Images of coffee tree & beans

The action of coffee depends principally on the caffeine contents which act on the
CNS, kidney, muscles & heart.

The usual cup of brewed coffee contains about 100-150mg of caffeine & a cup of
instant coffee contains about 85-100mg of caffeine.

For comparative purposes of caffeine contents, a cup of tea contains 60-75mg, of cacao
5-40mg, & 12oz of cola drink 40-60mg. the estimated maximum daily dose of caffeine
is 1.5gm. Although coffee is mainly a dietetic, it is also used as stimulant & diuretic. It
is also of value in the treatment of poisoning by certain CNS depressants.

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.

Black tea is prepared in Srilanka & India by heaping the fresh leaves until
fermentation has begun. They are then rapidly dried artificially with heat.

The stimulating action of tea is due to caffeine; its astringent properties are owing to
the tannins contents.
 Images of tea tree & fermentation process

Green tea is prepared in China & Japan by rapidly drying the freshly picked leaves in
copper pans over a mild artificial heat.

Images of preparation of green tea

Uses of purine bases:

Caffeine: It is used as an analeptic in the treatment of poisoning, as stimulant in acute

circulatory failure & as diuretic.

Theophylline: It & related compounds are utilized as smooth muscles relaxant, for
symptomatic relief or prevention of bronchial asthma & for treatment of reversible
broncho spasm associated with chronic bronchitis & also as diuretic.

Theobromine: It is a compound prepared from the dried ripe seeds of Theobroma

cacao F: Sterculiaceae. It is used as diuretic & smooth muscles relaxant. It has little
stimulant action on the CNS & so it is preferred over caffeine in treatment of cardiac
edema & angina pectoris.

Maté leaf

Maté (Yerba maté; Paraguay tea) consists of the dried and cured leaves of
Ilex paraguensis (Aquifoliaceae) and other species of Ilex, small trees or
shrubs indigenous to the region where Argentina, Paraguay and Brazil meet.
The drug is obtained partly from wild plants (e.g. in Brazil) and partly from
cultivated ones (in Argentina).

Maté contains about 0.2–2% of caffeine, about 10–16% of chlorogenic acid

(caffeotannic acid) and a little volatile oil. It is said to be very rich in
vitamins. Maté tea is very widely used in South America with some
consumption in Europe and America.

Comfrey

The roots and aerial parts of Symphytum officinale (comfrey), family

Boraginaceae, have long been important drugs in herbal medicine for the
treatment of pulmonary and gastric conditions and various rheumatic
complaints. In addition to mucilage and tannin these contain allantoin (0.6–
0.8% in the roots) which can be regarded as a breakdown product of uric
acid. Allantoin stimulates tissue regeneration and therefore the drug has
been used for external injuries and gastric ulcers.
 Lupinane alkaloids
(quinolizidine)

Quinolizidine nucleus
Lupinane contains a methyl group at position (1).

The important alkaloids of this group are lupinine, sparteine & cytosine.
These alkaloids are found in scoparius (Broom tops) which are the dried tops of Cytisus
scoparius F: Leguminoseae.

Lupinine sparteine cytisine

Biosynthesis precursor is 2 lysine molecules.
Sparteine is the most important alkaloid, found up to 1.5%.It is a bitter viscous liquid
alkaloid used in medicine to stimulate the heart & also the uterine muscles in childbirth, it
has oxytocic action.
The steroidal alkaloids are characterized by the cyclo-penta phenanthrene nucleus.

They are either formed from cholesterol or they & cholesterol have a common precursor.
In general, the steroidal alkaloids represent an important class of alkaloids that essentially
afford a close structural relationship to sterols i.e., they contain a cyclo penta phenanthrene
nucleus. Interestingly, this group of alkaloids invariably occurs in the plant kingdom as
glycosidal combination with carbohydrate moieties.
The steroidal alkaloids may be broadly classified into two major groups, namely:
(a) Solanum Alkaloids
(b) Veratrum Alkaloids
(c) Aconite

A. Solanum Alkaloids
A good number of plants belonging to the natural order Solanaceae have been found to
accumulate favourably several steroidal alkaloids based on a C27 cholestane skeleton, such
as: solasodine, tomatidine, solanidine. These alkaloids usually occur in a wide variety of
the genus Solanum, for instance: Solanum laciniatum; S. nigrum; S. aviculare etc. The three
above mentioned alkaloids normally occur naturally in the plant as their corresponding
glycosides.
However, the two species of Solanum, namely: S. laciniatum and S. aviculare are considered
to be a rich source of alkaloids (i.e., the aglycone moieties) that are employed exclusively as
the starting materials for the synthesis of several hormones and adreno-cortical steroids.
The solanum alkaloids, stated above are essentially the nitrogen-analogues of steroidal
saponins.
Solanum nigrum image

solasodine

Solasodine is a poisonous alkaloid chemical compound that occurs in plants of

the Solanaceae family. Solasonine and solamargine are glyco alkaloid derivatives of
solasodine. Solasodine is teratogenic. It is commercially used as a precursor for the
production of complex steroidal compounds such as contraceptive pills.

(b) Verateum alkaloids: (Hellebore)

Veratrum species contain highly toxic steroidal alkaloids (e.g. veratridine) that
activate sodium ion channels and cause rapid cardiac failure and death if ingested. All parts
of the plant are poisonous, with the root and rhizomes being the most poisonous. Symptoms
typically occur between 30 minutes and 4 hours after ingestion.

It is the dried rhizomes & roots of Viratrum viridi F: Liliaceae.

It contains a large number of alkaloids classified into 3 groups on the bases of their chemical
constituents:
1. Group I: consists of esters of the steroidal bases (alkamines) with organic acids, includes
cevadine, germidine, germetrine, veratridine, etc…..
2. Group II: consists of glucosides of the alkamine include pseudo jervine & veratrosine.
3. Group III: consists of the alkamines themselves include germine, jervine, rubijervine &
veratramine.

The first group only is pharmacologically active & is used as hypotensive & cardiac
depressant & sedative.

Veratrum veridi image

(c) Aconite alkaloids:

It is the dried root of Aconitum napellus F: Runuculaceae.

It is rich in alkaloids & these alkaloids can be classified into:
1. Atisine group: they are simple in structure than the second group, less oxygenated, less
toxic e.g. ajaconine.

Ajaconine

2. Aconitines: are more toxic, more complicated, contains more oxygen as methoxy &
hydroxy, at least 2 of these hydroxy groups are esters one with aliphatic acid & the other
with aromatic acid e.g. aconitine.
Aconitum napellus is grown in gardens for its attractive spike like inflorescences and showy
blue flowers

A. napellus contains several poisonous compounds, including enough cardiac poison that it
was used on spears and arrows for hunting and battle in ancient times. A. napellus has a long
history of use as a poison, with cases going back thousands of years. During the ancient
Roman period of European history, the plant was often used to eliminate criminals and
enemies, and by the end of the period it was banned and anyone growing A. napellus could
have been legally sentenced to death. Aconites have been used more recently in murder plots;
they contain the chemical alkaloids aconitine, mesaconitine, hypaconitine and jesaconitine,
which are highly toxic.
 Alkaloidal amines
The alkaloids in this group do not contain heterocyclic nitrogen atoms i.e. the nitrogen is
not a part of the heterocyclic ring, so it is called atypical alkaloids. Many are simple
derivatives of phenyl ethyl amine &, as such, are derived from phenylalanine & tyrosine.
Other alkaloidal amines are tryptamine derivatives &, as such, are biosynthesized from
tryptophan.

Drugs containing alkaloidal amines:

Ephedra which contains ephedrine.
Colchicum which contains colchicines.
Khat which contains cathinone.
Pyote which contains mescaline.
1. Ephedra:
It is the entire plant or the over ground portion of Ephedra sinica F: Gentaceae.
The main alkaloids are ephedrine & pseudoephedrine.

Ephedrine pseudoephedrine
Ephedrine is produced commercially either by extraction of plant material or by chemical
procedure. It could be synthesized from phenyl ethyl ketone in the presence of methyl
amine. 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. It is a potent
sympathomimetic. It excites the sympathetic nervous system causes vasoconstriction,
cardiac stimulation & rise in blood pressure. It works mainly by increasing the activity
of nor epinephrine (nor adrenaline) on adrenergic receptors. It is most usually marketed as
the hydrochloride or sulfate salt. It is commonly used as a stimulant, concentration
aid, decongestant, appetite suppressant, and to treat hypotension associated with anesthesia.

Biosynthetic precursor is phenylalanine.

2. Colchicum:

It is the dried, ripe seeds of Colchicum autumnale F: Liliaceae. Two parts are used
officially, the seeds & corm.

Colchicum contains the alkaloid colchicines up to 0.8% in the seeds & 0.6% in the corm.

Colchicine Tropolone ring

The biosynthesis precursor is phenylalanine (which will change to cinnamic acid by

deamination) in addition to tyrosine. The tropolon ring is formed by inclusion of a carbonyl
group in the six member ring.
Colchicine lacks basicity & does not form a well defined series of salts as do other
alkaloids. Colchicine is used in gout to increase secretion of uric acid. It also causes
doubling of chromosomes & this opens a large field in plant biogenetics. The interrelation
between the action of colchicines & mitosis is investigated in animals & preliminary
experiments show that injection of colchicines 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
native to tropical east Africa. It is cultivated extensively in the Ethiopian highlands & in
Yemen. Fresh leaves are regularly transported by air to areas distant from the centers of
cultivation.

The leaves are chewed habitually by many people to alleviate the sensation of hunger &
fatigue. The Expert Committee of Addiction-producing Drugs of the World Health
Organization does not classify khat as a drug that produces habituation or addiction, but the
French government considers it as a narcotic.

Khat contains a potent phenyl alkyl amine alkaloid called (-)-cathinone. It has
pharmacological properties analogous to those of (+)-amphetamine & is of similar potency
with a similar mechanism of action i.e. the induction of catecholamine release from the
storage sites.
Cathinone

The young fresh leaves that come from the tips of the branches contain the optimum
amount of cathinone. In older leaves, it is converted to the weakly active compounds (+)-
norpseudo ephedrine 80% & (-)-nor ephedrine 20%. This conversion also occurs during the
drying of young leaves.

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 disturbs normal mental function & causes concomitant hallucination & euphoria.
The drug contains several alkaloids, the active of which is mescaline, anhalamine,
anhalanine & anhaladine.

Mescaline

Mescaline (3,4,5-trimethoxy-β-phenylethylamine) is regarded as the first of a series of

hallucinogens or psychotomimetics.
The imidazole ring is the principle nucleus in this group. The most important drug of this
group is pilocarpine.

Pilocarpine is an alkaloid obtained from leaflets of Pilocarpus jaborandi F: Rutaceae.

Pilocarpine

All of the commercial kinds of Pilocarpus when freshly dried yield 0.5-1% of the alkaloid
pilocarpine. Isopilacarpine, pilocarpidine, & pilosine are also present in some species.

Even under ideal storage conditions, the leaves lose at least half of their alkaloidal contents
in one year through deterioration. Leaves that are two years old are practically worthless.

Pilocarpus jaborondi image

Pilocarpine is the lactone of pilocarpic acid, an acid with imidazole ring.

Pilocarpic acid

Pilocarpine stimulates the muscarinic receptors in the eye, causing constriction of the pupil.
. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system,
which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its topical
application, e.g., in glaucoma and xerostomia.
It is a cholinergic, it is found as eye drop & ointment used in the treatment of
glaucoma. The most common concentration for this use is pilocarpine 1%, the weakest
concentration.
Pilocarpine is used to stimulate sweat glands in a sweat test to measure
the concentration of chloride and sodium that is excreted in sweat. It is used to
diagnose cystic fibrosis.
Pilocarpine stimulates the secretion of large amounts of saliva and sweat. It is used to treat
dry mouth (xerostomia) , but also as a side effect of radiation therapy for head and neck
cancer.
It has also been used in the treatment of chronic open-angle glaucoma and acute angle-
closure glaucoma for over 100 years.
It is on the World Health Organization's List of Essential Medicines, a list of the most
important medication needed in a basic health system.
The active parts in the structure of pilocarpine are the lactone ring & imidazole ring.
Structural similarities suggest that pilocarpine is formed from histidine or a metabolic
equivalent.