INTRODUCTION TO ALKALOIDS
belladonna
- Basic nitrogenous compounds
incorporated on heterocyclic rings
- One of the largest secondary
metabolites
- Physiologically active , end in “-ine”
- “Alkalo”: basic, “oid”: like
- Usually in the form of amines:
o Primary amines: H2N- R
o Secondary amines: HN-R
o Tertiary amines: N-R3
o Quaternary amined: N:R4
- Heterocyclic ring- basis of
classification
- Families containing alkaloids:
o Apocynaceae
o Berberidaceae
o Papaveraceae
o Rubiaceae
o Solanaceae
o Poaceae
o Leguminosae/ Fabaceae
- Alkaloid free families
o Lamiaceae
o Rosaceae
- Plant parts
o Seeds: Physostigma &
areca
o Leaves: Coca
o Underground stem:
Singuinasia
o Roots: Ipecac
o Barks: Cinchona
o Whole plant: Angel’s trumpet
- Occurs in free form: very soluble in
water
o Free base + acid (such as
Sulfuric acid(H2SO4),
Hydrochloric acid(HCl),
Oxalic acid, Merconic acid,
and Quinic acid)
Salt(soluble) +
alkaline( to liberate the
alkaloid form salt
- Naming of alkaloids is based on:
o Genus: Atropine; Atropa
o Species: Cocaine;
Erythroxylum coca
o Common name: Vincristine
and vinblastine; Vinca
alkaloids
o Name of the discoverer:
Pelletierine(Punica
granalum); Pellitier
o Physical characteristics:
Hygrine
o Physiologic Activity:
emetine; emesis
o Pharmacologic use
- Classification of alkaloids:
o True alkaloids- heterocyclic
ring+ nitrogenous
substances
o Protoalkaloids- heterocyclic
rings without nitrogenous
substance
o Pseudoalkaloids- no
heterocyclic rings with
nitrogenous substance
- Classification according to the
nature of the basic chemical
structure:
o Pyridine- piperidine
alkaloids
o Tropane alkaloids
o Quinoline alkaloids
o Isoquinolines
o Indole alkaloids
o Imidazole
o Purine
o Steroidal alkaloids
o Alkaloidal amines
- Physical characteristics
o Solid state: crystalline
except for emetine
o Some exist as liquid(those
that lacks oxygen): CANS
 Conine/ Hemlock:
Corium maculatum
 Arecoline/ Areca
  Nicotine (MAMEKI) solution
 Sparreine
o Volatile: nicotine 2. WAGNER’S Iodopotassi Reddish
o Color: TEST (WIKI) um Iodide brown
 Yellow (Berberin; Solution ppt
Colchicine) 3. DRAGENDOR Bismuth Orange
 Red(Sanginarin) FF’S TEST Potassium ppt
 Orange(Canadine) (DRABIKI) Iodide
o Solubility 4. HAGER’S Picric Acid Yellow
 Soluble: organic TEST ppt
solvents( Benzene,
- Imparts vivid color
ether, chloroform)
- These reagents are oxygenated high
 Insoluble in water
molecular weight acids
Except:
- Other reagent:
 Soluble in water:
o Froende’s reagent-
Caffeine, ephedrine
Phosphomolybdate + conc.
 Insoluble in water:
Sulfuric acid
quinine salts
o Marquis’ reagent-
 Insoluble in
Formaldehyde + conc.
benzene:
Sulfuric acid
Theobromine and
o Mandalin’s reagent-
theophylline
Ammonium vanadate +
- Chemical properties
sulfuric acid
o Contains Nitrogen and
o Erdmann’s reagent- conc.
Oxygen
Nitric acid with conc. Sulfuric
o Reacts with acid
acid
 Acid- dehydration
- FUNCTIONS:
(“apo”- dehydrated
o Poisonous agents to protect
form ex:
plants from insects and
apomorphine)
herbivore
 Reacts with alkali
o End product of detoxification
o Forms double salts with
reactions: metabolic locking
compounds of Mecury,
o Regulatory growth factor
Silver, Platinum and other
o Reserve substance
heavy metals
- Biosynthesis: amino acids
- Qualitative Test: heavy metals are
- Actions:
responsible for precipitation of
o Alkaloids greatly affect the
alkaloids.
parasympathetic nervous
TEST REAGENT POSITI
system (PANS)
S USE VE
 Cholinergic-
RESUL
enhances activity of
T
acetylcholine
1. MAYER’S Potassium Cream  Anticholinergic-
TEST Mercuric ppt opposes cholinergic
Iodide activity
 o Analgesics- central stimulant optical nerve
- Nervous system
o Central Increase tear Decrease tear
 Brain secretionLacrimation secretionXerop
 Spinal cord htalmia:
o Peripheral RESPIRATION
 Somatic
 Voluntary CHOLINERGIC ANTICHOLINERG
 Autonomic IC
 Involuntary Bronchoconstriction Bronchodilation
 Sympathetic (High mucus secretion)
- fight or Dyspnea
flight
 Parasympat GASTROINTESTINAL TRACT
hetic- rest
CHOLINERGIC ANTICHOLINERG
and digest
IC
- PANS RECEPTORS-
neurotransmitter & acetylcholine Increase in peristalsis Decrease in
o Muscarinic receptors- (movement within the peristalsisConst
stimulation or inhibition GIT) Diarrhea ipation
 M1: Stomach
 M2: Heart Increase gastric Decrease gastric
 M3: Smooth muscle secretions High HCl: secretionsLow
o Eyes: circular smooth PUD HCl: Ach;orhydria
muscle (Txt: Dilute HCl
o Bronchi: detrusor using a glass
o GIT: wall and sphincter straw)
o Bladder: trigone Increase salivary Decrease salivary
- Agonist: stimulation secretionAmylase: secretionXerost
- Antagonist: inhibition digestion of CHO omia (Dry Mouth)
EYES
CARDIOVASCULAR
CHOLINERGIC ANTICHOLINERG
IC - Chronotrophy: rate of heart
contractiom
Miosis (Pupil Mydriasis (Pupil
constriction) dilation) CHOLINERGIC ANTICHOLINERG
IC
Increase aqueous Decrease
humor flow Drainage aqueous humor (-) Chronotrophy: (+)Chronotrophy:
flowAccumulati Bradycardia
Tachycardia
on: Glaucoma:
There’s an URINARY TRACT
increase
intraocular CHOLINERGIC ANTICHOLINERG
pressure that IC
damages the Diuresis/Micturationc Urination
ontraction of detrusor retentionrelaxat -Targets the nervous system as a Cholinergic
and relaxation in the ion of detrusor Agonist*
bladder and contraction in Additional info:
the bladder Smoking increases digestion this is
CENTRAL NERVOUS SYSTEM because it activates the flight or fight
responses.
CHOLINERGIC ANTICHOLINERG
USES:
IC
 CNS Stimulant
Stimulation Depression  Smoking deterrent

SWEATING 3. Areca nut (Areca catechu, Arecaceae)

CHOLINERGIC ANTICHOLINERG -Also called as Betel Nut
IC -Source of Arecoline, Arecaidine, Guvacine,
Guvacoline
Diaporhesis Xeroderma USES:
 Masticatory stimulant
 Strengthens teeth
A. PYRIDINE-PIPERIDINE ALKALOIDS  Vermifuge for animals
(Anthelminthic)*
-Upon reduction, pyridine, is converted into
the secondary base, piperidine. For ringworms:
Taenia solium-pigs
SOURCES: Taenia saginata-cows

1. Tobacco (Nicotiana tobacum, -Leaves of Ikmo (Piper betel,

Solanaceae) Piperaceae) are used to improve the
taste of Areca nut.
-Source of Nicotine* (is a primarily a product
of root metabolism) 4. Fenugreek (Trigonella foenum-
-Targets the nervous system as a Cholinergic graecum, Fabaceae)
Agonist -Source of Trigonelline
USES:
 Smoking deterrent in a form USES:
of gum (aid for smokers  Herb and spices
seeking to quit)
 CNS Stimulant 5. Black Pepper (Piper nigrum,
Piperaceae)
Additional info: -Source of Piperine
Nicotine does not cause the toxicity, the
smoke causes it. USES:
 Carminative

2. Lobelia (Lobelia inflate, Campanulaceae) 6. Castor (Ricinus communis,

Euphorbiaceae)
-Also called as Indian tobacco -Source of Ricinine
-Source of Lobeline
 USES:  Antisialogogue (to
 CNS Stimulant control bodily fluid
secretions)
7. Pomegranate (Punica granatum,
Punicaceae) 2. Hyoscyamine
-Source of Pelletierine -Tropine ester of tropic acid
-Readily hydrolysed by boiling of dilute acids
USES: or alkaline
 Cholinergic Agonist
A2. Hyoscyamine sufate
B. TROPANE ALKALOIDS -Obtained from Hyoscyamus
-derived from phenylalanine species
-It is extremely poisonous
-Occurs as white, odorless crystals
or as crystalline powder
-It is deliquescent and affected by
light

B1. SOLANACEOUS ALKALOIDS USES:

PRINCIPLE ALKALOIDS:  Anticholinergic
 Aid in the control of
1. Atropine gastric secretions
-Obtained from Atropa Belladona,
Solanaceae 3. Scopolamine or hyoscine
-It can also be produced synthetically -Particularly abundant in Datura
-It is extremely poisonous fastuosa
-Characteristics: -Upon hydrolysis, it yields tropic acid
 Colorless, needle-like, crystals or as and scopoline.
a white, crystalline powder -It is colorless and syrupy
 Optically inactive USE:
USES:  CNS depressant
 Antidote for (Scopolamine)
poisoning caused by
cholinesterase
inhibitors. A3. Scopolamine hydrobromide or
 CNS stimulant Hyoscine hydrobromide
-Colorless or white crystals/ granular
A1. Atropine sulphate powder that is odorless
-occurs as colorless crystals or as -It is extremely poisonous
white crystalline powder
-Extremely poisonous USE:
-Effloresces in air  Anticholinergic
USES:
 Anticholinergic SOURCES
1. Hyoscyamus (Hyoscyamus niger,
Solanaceae)
-Also called Henbane -Active principles: Nicotine &
-Dried leaf Nornicotine
-It is poisonous to swine
-Active principles: Hyoscyamine & 4. Mandragora or European
Scopolamine Mandrake (Mandragora
officinarum, Solanaceae)
USE: -Root
 Parasympatholytic -Active principle: Hyoscyamine,
Scopolamine & Mandragorine
2. Stramonium (Datura stramonium,
Solanaceae) 5. Cocaine (Erythroxlum coca,
-Also called as Jimson weed or James-town Erythroxylaceae)
weed -Coca
-Active principles: Hyoscyamine & -Leaves
Scopolamine -It was an inferior substitute for tea
-Contains 3 types of alkaloids:
USES: a. Derivatives of ecgonine
 Anticholinergic (cocaine, cinnamylcocaine,
 Powdered stramonium- alpha & beta-truxilline)
ingredient in preparations b. Tropine (Tropacocaine,
intended for burns. –The valerine)
vapour is inhaled for the c. Hygrine (Hygroline,
relief of asthma. Cuscohygrine)

OTHER SOLANACEOUS DRUGS USES:

 Multiple Central & Peripheral
1. Withania (Withania somnifera, Nervous system actions
Solanaceae)  Psychomotor stimulant with
-Dried root a strong abuse potential
-Related botanically to belladonna
and hyoscyamus  Huanuco coa
-Principle Alkaloid: Cuscohygrine
USE:  Truxillo coa
 Sedative -Lower content of ester alkaloids
-Has 75% cocaine
2. Duboisia (Duboisia  Cocaine hydrochloride
myoporoides, Solanaceae) -It occurs as colorless or white
-Dried leaves
-Active principles: Hyoscyamine & USES:
Scopolamine  Local anesthetic
-Currently the chief source of  Ingredient in
Atropine Brompton’s
cocktail* (Control
3. Pituri or Australian Tobacco severe pain
(Datura hopwoodii, Solanaceae) associated with
-Leaf terminal cancer.)

C. QUINOLINE ALKALOIDS
Biosynthesis of Quinoline
Alkaloids
 Alkaloid Precursors:
Tryptophan: Precursor of quinine in
cinchona.
Pathway of Tryptophan Biosynthesis:
Chorismic acid
↓ methanol and chloroform.
Anthralinic acid (Amide Nitrogen of Glutamine)
↓5-Phosphoribosyl-1-
pyrophosphate
1(o-Carboxyphenylamino)-1-deoxyribulose
5-phosphate
↓ Quinism
Indole-3-glycerol phosphate
↓Serine
Tryptophan
 Quinoline Derivatives
Biosynthetic Origin of Quinine
L- Tryptophan + Secologanin
↓
Strictosidine
↓ - Controlled and more uniform
Coryantheal
↓ mucosa than the quinidine
Quinine
1. Cinchona (Cinchona succirubra,
Rubiaceae (red)), Cinchona
calisaya, Rubiaceae (yellow))
Aka: Cinchona bark; Peruvian Bark
Plant part: Dried bark of stem or root
- Best source of quinine
- Source of: Quinine, Quinidine.
Cinchonine, Cinchonidine
Cinchona Alkaloids:
A. Quinidine
- Sterioisomer of quinine
- Present in cinchona barks (0.25-1.25%)
- Depresses myocardial excitability,
conduction velocity, and, to a lesser
extent, contractility.
Quinidine sulfate
- From Remijia pedunculata or fron
quinine.
- Fine, needlelike, white crystals, odorless,
has a bitter taste.
- Darkens when exposed to light.
- Readily soluble in: water, alcohol,
USES:
 Class IA anti arrhythmic agent
 Targets sodium channel blocker
-Toxicity: Cinchonism/
- Hallmark: Tinnitus,
temporary loss of hearing
(reversible)
Quinidine gluconate
- White powder, odorless and has a
bitter taste
- Available in sustained release tablet
Quinidine polygalactouronate
absorption through the intestinal
sulfate.
- Produces lower incidence of
gastrointestinal irritation.
B. Quinine
- Diastereoisomer of quinidine
- White, odorless, bulky, bitter crystals
or as a crystalline powder.
- Darkens when exposed to light.
- Effloresces in dry air.
- Freely soluble in: alcohol, ether &
chloroform
- Slightly soluble in: water
Quinine sulfate
- Bark of Cinchona
 - White, odorless, bitter, fine, needle
like crystals, lusterless.
- Becomes brownish when exposed to
light.
- Not readily soluble in:
water, alcohol, chloroform,
ether.
USE:
 Anti malarial agent; But can
cause blood dyscrasias.
*Malaria:
Plasmodium falaparum
Plasmodium malariae
Plasmodium ovale
Plasmodium vivax
*Vector: Female Anopheles
Fly
- Skeletal muscle relaxant
2. Cuprea (Remijia purdieana,
Rubiaceae)
Plant part: Bark
- Best source of Quinidine
USE:
 Anti-arrhythmic
3. Cusparia (Galipea officinalis,
Rutaceae)
Plant part: Bark
- Source of Cusparine
D. ISOQUINOLINE ALKALOIDS
-from tyrosine and phenylalanine
2. IPECAC
Plant part: Dried rhizomes and roots
Cephaelis ipecacuanha, Rubiaceae
Cephaelis acuminate, Rubiaceae
Source of: Emetine, cephaeline,
psychotrine
Amoebic Dysentery
-Entamoeba histolytica
MOA:
Local irritation in the GIT
Stimulation of the Chemoreceptor Trigger
Zone (CTZ)
Stimulation of the Medulla oblongata
Emetine HCl- antiprotozoal, emetic,
expectorant
- formerly as an antiaboebic
Ipecac Syrup- emetic
- emetine + cephaeline
Ipecac Fluid Extract- 14x stronger than
Ipecac Syrup
Ipecac + Opium- “Dover’s Powder”
-diaphoretic: high fever,
remove excess toxic
substances
3. CURARE
AKA: South American Arrow Poison,
Calabash, Tubocurare, Pot Curare
Plant part: Dried extract from the bark
Strychnos castelnei, Longaniaceae
Source: Tubocurarine
- Has muscle relaxant activity
Standard test: “Head Drop Cross-Over
Test”
- Management of convulsion
associated with strychnine toxicity
and tetanospasmin exposure
- Diagnosis of Myastenia gravis
Myasthenia gravis
- Autoimmune disease causing
chronic, progressive, damage of
neuromuscular junction (NMJ)
- Pathophysiology: Acetylcholine
receptor blockade
- Signs and symptoms: weakness of
eye muscles, difficulty in chewing
 or talking, respiratory paralysis,
death
- late afternoon fatigue
- ptosis-drooping of eyelid
4. OPIUM/ GUM OPIUM
AKA: Stone of Immortality
Plant part: ripe or unripe capsule
Papaver somniferum, Papaveraceae
Unripe capsule- source of morphine,
codeine
Ripe Capsule- source of thebaine,
papaverine,
anarcotine or noscapine
Laudanum - camphorated opium tincture
Paregoric – opium tincture
OPIATES
 Natural
 Morphine and codeine
OPIOIDS
 Molecular modification
 Heroin
- more addictive than morphine
- acetylation of morphine
4. OPIOIDS
 Diacetylmorphine or Heroine
- From the acetylation of morphine;
very potent
 Hydromorphone (Dilaudid®)
- More potent analgesic with less
frequent side effects
- Very addictive
 Apomorphine
- Condensation of morphine and
hydrochloric acid
- Emetic
 Hydrocodone
- antitussive
5. GOLDENSEAL
AKA: Hydrastis
Plant Part: Dried rhizome
Hydrastis canadensis, Ranunculaceae
Source: hydrastine, berberine, canadine
(crystalline alkaloids)
-hydrastine and berberine are both
astringents and anti-inflammatory
-berberine and canadine are both coloring
dyes and staining reagents
6. SANGUINARIA
AKA: Blood Root
Sanguinaria canadensis, Papaveraceae
Source: Sanguinarine
Uses: Expectorant
Emetic
E. INDOLE ALKALOIDS
 Has indole rings
 Derived from the combination of
tryptophan and acetate metabolism.
Sources and Alkaloids:
1. Rauwolfia- dried roots of Rauwolfia
serpentina, Apocynaceae
 Source of Reserpine,
rescinamine, desperidine
 Reserpine- chief alkaloids
(Serapasil, Serpalan)
 Powdered Rauwolfia
serpentina- not less than
0.15% and not more than
0.20 % of reserpine-
rescinamine group alkaloids.
 Uses:
 Hypertensive effect
 Sedative
 Tranquilizer
2. Periwinkle- dried whole plant of
Cantharus roseus, Apocynaceae
 Source of Vinca alkaloids
(vincristine, vinblastine,
vinleurosidine, vinrosidine)
 Uses:
  Anti-neoplastic:
arresting cell
division
 Vinblastine sulfate- treat a
wide variety of neoplasms
 Vincristine sulfate- treatment
of acute leukemia
3. Nuxvomic- dried ripe seed of
Strychnosux-vomica, Logianaceae
Strychnosignatii (St. Ignatius bean)
 Source of strychnine and
brucine
 Uses:
 Strychnine- toxic
central stimulant
- Vermin killer
 Brucine- alcohol
denaturant
4. Physostigma “Calabar bean”
 Dried ripe seed of
Physostigmavenenosum,
Fabaceae
 Source of physostigmine
(serine), eseramine,
geneserine, and
physovenine
 Use:
 For the
management of
glaucoma
 Physostigmine salicylate-
cholinergic
- Antidote in the
poisoning
caused by anti-
cholinergic
5. Ergot “Rye ergot”
 Dried sclerotium of
Claviceps purpurea,
Poaceae
 Source of ergonovine and
ergometrine
 Ergot alkaloids
 Ergonovine maleate /
Ergometrine maleate-
oxytocic
 Methylergonovine –
oxytocic,slighthly more
active and longer acting than
ergonovine (Methergin)
 Ergotamine tartrate- anti-
migraine
F. IMIDAZOLE ALKALOIDS
 Derivative of histidine
 Contains imidazole (glyoxaline) ring
Source:
1. Pilocarpine “Jaborandi”
 From the leaflets of
 Pilocarpus jaborandi,
Rutaceae
 Uses:
 Stimulates
muscarinic
receptors in the eye
 Cholinergic
 Help in the
management of
glaucoma
G. STEROIDAL ALKALOIDS
 Has CPPP
(Clyclopentanoperhydrophenantrine)
ring
 Derived from six isoprene units and
could be classified as triterpenoids or
steroids
Sources:
1. American green hellebore
“Veraltramveride”
 Dried rhizome of Veratrum
viride, Liliaceae
 Sources of cevadine,
germidine, veratidine,
 Uses:
  Hypotensive
property
 Cardiac depressant
 Sedative
 For the treatment of
hypertension
2. White hellebore “European
hellebore”
 Dried rhizome of Veratum
alba, Liliaceae
 Use:
 Hypotensive
property
H. ALKALOIDAL AMINES
Sources and Alkaloids:
1. Ephedra “Ma Huang”
 Source of ephedrine
 Ephedrine sulfate- used as
nasal decongestant and for
the relief of asthma
2. Colchicum seeds
 Colchicum autumnale,
Liliaceae
 Source of colchicine
 Use:
 Used for the
treatment of acute
gout
3. Khat (Catha edulis, Celastracene)
contains cathinone
4. Peyote/ mescal buttons
 Dried tops of
Lophophorawilliamsii,
Cactaceae
 Contains mescaline-
hallucigenic and euphoric)
I.PURINE BASES
 Derivatives of heterocyclic nucleus
with a consisting pyrimidine ring
fused to imidazole ring
 CNS stimulant, diuretics,
bronchodilation and stimulate GI
secretion
 Methylxanthines- competetively
inhibit phosphodiesterase
Caffeine containing Drugs:
1. Kola/ Cola, kolanuts
 Dried cotyledon of Cola
nitida, Sterculiaceae
 Contains caffeine and
theobromine
 Uses:
 CNS stimulant
 Ingredient in several
carbonated
beverages
2. Coffee bean/ Coffee seed
 Dried ripe seed ofCoffea
arabica, Rubiacea
 Caffeol- aroma
 Uses:
 Stimulant
 Diuretic
3. Guarana
 Dried paste, crushed seed of
Paulliniacupana,
Sapindaceae
 Contains caffeine- has
stimulating beverage and
astringent properties
4. Mate “Paraguay tea”
 Ilex paraguanensis,
Aquafoliaceae
 Contains caffeine and tannin
 Uses:
 Laxatives or
purgative as large
doses
 Diaphoretic
  Diuretic property

Caffeine (1,3,7-trimethylxanthine)

 Mild stimulant
 Sources are coffee, tea, cacao,
guarana, kola and mate
 Uses:
 Antimigraine
 Stimulates all levels of CNS

Theophylline (1,3-dimethylxanthine)

 Leaf buds of Camellia sinensis,

Theaceae
 Isomeric with theobromine
 Use:
 Smooth muscle relaxants for
symptomatic relief and
prevention of asthma
 Treatment of reversible
bronchospasm in chronic
bronchitis and emphysema

Aminophylline

 Uses:
 Diuretic
 Dilating action in the
pulmonary vessels, relieving
asthma

Theobromine (3,7-dimethylxanthine)

 Dried ripe seed of Theobroma

cacao, Sterculiaceae
 Uses:
 Diuretic
 Smooth muscle relaxant
 Little stimulating action in
the CNS