Mohammed N. Sabir

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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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