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Mohammed N. Sabir
4/8/2019
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A group of alkaloids in which the nitrogen atom is
Not heterocyclic
(Protoalkaloids) also called atypical alkaloids.
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Example Species Pharmacological actions
Colchicine Colchicum automnale Antimitotic, uric acid amines solvent
Ephedrine Ephedra sinica Sympathetic stimulant, bronchodilator
Cathinone Catha edulis CNS stimulantCapsaicine Capsicum annum Circulatory stimulantMescaline Lophophora williamsii Hallucinogenic
Alkaloidal amines “Protoalkaloids”
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1-Ephedrine
2-Cathinone
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3-Colchicine
4-Capsaicine
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1-Ephedra (ma huang)
The overground part of
Ephedra sinica (Ephedrales
or Ginetaceae)
In Chinese:
ma = astringent
huang = yellow
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This plant has been used in Chinese
herbal medicine since 5000 years
ago;
While in modern medicine since 1923.
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The plant is indigenous to
China and to many parts in
Asia including Kurdistan
Region-Iraq.
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The plant is a shrub with
about 50-100cm height.
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The active principle of the
plant is Ephedrine
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Ephedrine (-)-Erythro-α-[1 (methylamino) ethyl]benzyl alcohol
Production is either by extraction from the plant or chemical synthesis.
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Chemical synthesis from benzylhydroxymethyl ketone and methylamine.
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Methyl amine
Ephedrine occur as white
needle-like crystals soluble in
water, alcohol, chloroform,
ether and petroleum ether.
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It is structure similarity to the
endogenous catecholamines is
responsible for potent
sympathomimetic agent, stimulating
both α and β-adrenergic receptors.
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Ephedrine and
Pseudoephedrine are mixed
action adrenergic agonists.
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17Medicinal uses (Ephedrine sulphate and Ephedrine. HCl)…
o Bronchodilator.
o Allergy.
o Cough suppressant.
o Increase BP during shock.
o Vasoconstrictor.
o Decrease inflammation and mucus secretion.
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Adenylate cyclase
ATP c-AMP
PKA (c-AMP dependent PK)
Ca++
Na+
Ca++
β1-adrenergic activity
Pharmacologic Action
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α2-adrenergic activity
Pharmacologic Action
Adenylate cyclase
ATPc-AMP
PKA(c-AMP dependent PK)
Ca++
Na+
Ca++
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Adrenergic agonist interaction with receptor site domains
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Adrenergic agonists conc. Vs. activity
beta2Muscle
beta2Muscle
Tissue Receptor Subtype
Heart beta1
Adipose tissue beta1beta3?
Vascular Smooth
Airway Smooth
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At large doses:-
Toxicities ofEphedrine
1-2-3-4-5-6-
Hypertension
Headache Dizziness Palpitation VomitingNervousness & insomnia (CNS
effects)
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Available as (Ephedrinesulfate & Ephedrine HCl)
Pharmaceutical dosageforms:-
1-Tablets2-Oral liquid dosage forms3-Inhalations4-Injections
Clinical uses:-
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Ephedrinederivatives
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Compounds with less α-receptor affinity
N-MethylephedrineNorephedrine
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Colchicine
Is the dried ripe seed of
Colchicum automnale
(Fam: Liliaceae)
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Colchis = refers to the plant
flourishes
Autumnale = refers to the Season
where the plant bloom
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The plant is indigenous to Europe and North Africa
The Arabs recommended the use of the corn for Gout.
Colchicum contains the Colchicine (0.6-0.8%).
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Colchicine is a weak base and almost
lacks basicity since it does not react
with acids as other alkaloids do,
however; it is precipitated by the
detecting reagents.
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Biosynthesis
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- Inhibition of leucocyte migration.
- Reduction of lactic acid production.
- Decrease deposition of uric acid.
- Reduction of phagocytosis leading to decrease
the severity of inflammation.
Mechanism of action
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Colchicine is also antimitotic agent through affecting the
chromosomes of the cell, in which it will still divided but
without the formation of the spindle fibers and subsequent
cell division.
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For such activity, colchicine has been used in
investigation for its anticancer activity in
animals.
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Pathophysiology of Gout
Uric acid, the end product of purine
metabolism, is considered a waste product and
serves no known physiologic purpose in
humans.
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lacking the enzyme Urate-oxidase (Uricase), which further
degrades uric acid to allantoin, a substance that is more
water soluble and more readily excreted by the kidneys.
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Uricase
Excessive uric acid accumulation contributes to
hyperuricemia (defined as an elevated serum uric
acid (sUA) level above 7mg/dl in men and above
6mg/dl in women)
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It is considered to be the principle cause of
gouty arthritis which describes acute and chronic
clinical manifestations caused by the deposition
of monosodium urate crystals in articular and
extra articular tissues.
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Urate crystals
-Asymmetric swelling within joint on a radiograph
-First metatarsophalangeal joint
is tender or swollen-Hyperuricemia
-Maximal inflammation
developed within 1 day-Monoarthritis attack
-More than one acute arthritis attack
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-Redness observed over joints
-Subcortical cysts -Unilateral
first metatarsophalangeal
joint attack
-Unilateral tarsal joint attack
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Recent research has identified hyperuricemia as an
independent risk factor for metabolic syndrome,
coronary artery disease and chronic kidney disease.
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Gout refers to disease that occurs in response to
the presence of crystals of monosodium urate
(MSU) in joints, bones, and soft tissues.
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Consist of the fresh leaves of
Catha edulis (Celastraceae)Khat
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The plant is a tree native to
tropical East Africa.
The plant part that is rich
with the alkaloid is the leaf.
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Fresh leaves contains more
alkaloids when compared to
the old ones which contains
the less active metabolite
(+)-norephedrine.
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The leaves are Chewed
habitually by the
inhabitants.
Inhibiting the sensation of
hunger and fatigue.
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The WHO does not classify Khat a
habitual drug that cause
addiction, however; France
consider it as one of the
narcotics.
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Catha edulis contains
phenylalkylamine alkaloid (-)-
cathinone.
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Cathinone actions are analogues to (+)-amphetamine
including:-
Induction of catecholamine release from storage sites (CNS
stimulant action).
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Psychological effects includeEuphoriaAnxietyIncreasedAlertness
libido
Concentration
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- Energy- Self-esteem- Self-confidence- Sociability- Irritability
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- Aggression
- Psychomotor agitation
- Repetitive and obsessive behavior
- Paranoia
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With chronic and/or high doses, amphetamine psychosis
can occur.
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Capsaicin…
Derived from Capsicum annuum (Solanaceae)
Chili pepper.
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Used topically as circulatory stimulant and
analgesic for arthritis , neuropathy, neuralgia
and as anesthetic.
Also used in psoriasis to decrease itching and
inflammation.
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It binds selectively to a protein capsaicin receptor (CR)
on the membranes of pain and heat-sensing neurons.
CR is a heat-activated calcium channel that opens
between (37 – 45)°C .
Upon binding it causes the channel to open below 37°C, which is
why capsaicin is linked to the sensation of heat.
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Prolonged activation causes depletion of
presynaptic substance P.
Neurons that do not contain capsaicin receptors
will be unaffected.
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A study in 2003 showed that capsaicin
regulate blood sugar levels through
affecting carbohydrate breakdown after meals.
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Oil of Capsicum
Oil of Capsicum derived from chili pepper (Capsicum spp.)
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Medicinal uses:-
1- Analgesic (topical ointments, dermal patches) in
concentrations 0.025-0.25%.
2- In nasal sprays as decongestant anti-inflammatory.
3- In arthritis.
4- Neuralgia.
5- Reduce itching and inflammation (as creams in
psoriasis).4/8/2019
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Class Example Species Pharmacological actions
Purine alkaloids
Caffeine Coffea arabica CNS stimulantTheophylline Thea sinensis BronchodilatorTheobromine Theobroma cacao Vasodilator
Steroidalalkaloids
Solanine Solanum spp. Anti-inflammatoryVeratrine Veratrum album Antihypertensives
Terpenoidalalkaloids
Aconitine Aconitum spp. Antipyretic, analgesic, neurotoxin
Pseudoalkaloids
Purinebases
- Include alkaloids derived from
immidazole ring, the nucleotides
(xanthine bases)
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Those which retaintherapeutic activities are:-1-Caffeine (1,3,7-trimethylxanthine)
2-Theophylline (1,3-dimethylxanthine)
3-Theobromine (3,7-dimethylxanthine)
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Base Numbering
structures of the five major purine (R) and pyrimidine (Y)
bases of nucleic acids in their dominant tautomeric forms
and with the IUPAC numbering system
Source: Blackburn and Gait, Nucleic acids in chemistry and biology, Oxford University Press New York 1996.4/8/2019
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Methylxanthines
are biosynthesized from Aspartic
acid, Glycine, Glutamine
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1- Caffiene
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A purine alkaloid belongs to xanthine
class.
White crystalline powder with bitter
taste.
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Caffeine is found in
varying quantities in
the seeds, leaves, and
fruit of some plants
like (Camelia sinensis,
Coffea arabica)
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ServiceSizeCoffees Caffeine (mg)
200) (16 oz. = 266)
Starbucks Brewed Coffee (Grande) 16 oz. 320
Dunkin' Donuts regular coffee 16 oz. 206
Coffee, generic instant 8 oz. 93 (range: 27-173)
Starbucks Espresso, doppio 2 oz. 150
Starbucks Espresso, solo 1 oz. 75
Espresso, generic 1 oz. 40 (range: 30-90)
Starbucks Espresso decaffeinated 1 oz. 4
Einstein Bros. Espresso 1 oz. 75
Starbucks Frappuccino Blended Coffee Beverages, average 9.5 oz. 115
Coffee, generic decaffeinated 8 oz. 5 (range: 3-12)
Starbucks Vanilla Latte (Grande) 16 oz. 150
Einstein Bros. regular coffee 16 oz. 300
Coffee, generic brewed 8 oz. 133 (range: 102-
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Teas Service Size8 oz.
Caffeine (mg)53 (range: 40-120)Tea, brewed
Snapple, Lemon (and diet version) 16 oz. 42
Snapple Raspberry (and diet version) 16 oz. 42
Nestea 12 oz. 26
Arizona Iced Tea, green 16 oz. 15
Snapple, Kiwi Teawi 16 oz. 10
Snapple, Just Plain Unsweetened 16 oz. 18
Arizona Iced Tea, black 16 oz. 32
Snapple, Peach (and diet version) 16 oz. 42
Starbucks Tazo Chai Tea Latte (Grande) 16 oz. 100
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Chocolates/Candies/Other Service Size Caffeine (mg)
Hershey's Special Dark ChocolateBar 1.45 oz. 31
Hershey's Kisses 41g (9 pieces) 9Hot Cocoa 8 oz. 9 (range: 3-13)
Hershey's Chocolate Bar 1.55 oz. 9
Jolt Caffeinated Gum 1 stick 33
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Over-The-Counter Drugs Service Size Caffeine (mg)
Vivarin 1 tablet 200
Anacin (Maximum Strength) 2 tablets 64Excedrin (Extra Strength) 2 tablets 130
NoDoz (Maximum Strength) 1 tablet 200
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Theophylline Thebromine
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Used as bronchodilators
Mechanisms of action
Competitive nonselective phosphodiesterase
inhibitor, thereby increasing intracellular c-AMP, and
inhibiting TNF-α and leukotriene synthesis, thus
reducing inflammation and innate immunity
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Nonselective adenosine receptor antagonist,
antagonizing A1, A2, and A3 receptors which is
responsible for its cardiac effects
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Thank you
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