1

ADANA UNIVERSTY – INDUSTRY JOINT RESEARCH CENTER

ALKALOIDS

& ALKALOIDS

PLANTS

By

TAREK ISMAIL KAKHIA

2

3

INDEX

Itam

No

Page Itam

1 - Alkaloids :

1 Alkaloids

2 Atropine

3 Caffeine

4 Cocaine

5 Codaine

6 Heroine

7 Lidocaine

8 Morphin

9 Nicotine

10 Papaverine

11 Solanine

2 - Alkaliod Plants

1 Belladonna

2 Cannabis

3 Cannabis ( Drug )

4 Cannabis ( Altivation )

5 Coca

6 Coffee

7 Datura Stramonium

8 Datura

9 Hashish

10 Khat

11 Opium

12 Opium Poppy

4

13 Tea

14 Tobacco

15 Yerba Mate

3 - Alkaliod Plants Time Line

1 Time Line of Cannabis 1

2 Time Line of Cannabis 2

3 Time Line of Coca

4 Time Line of Coffee

5 Time Line of Datura

6 Time Line of Hashish

7 Time Line of Khat

8 Time Line of Poppy & Opium

9 Time Line of Tea

10 Time Line of Tobacco

11 Time Line of Yerba Mat

12 Time Line of

4 - Extension and Supplements

1 Night Shade Alkaloid Toxins Atropine , Scopolamine and Solanine

2 Hyoscyamus Niger

3 Nerium Oleander

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PART – 1

ALKALOIDS

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7

Alkaloid

Chemical structure of ephedrine, a phenethylamine alkaloid

Contents :

1 Introduction

2 Alkaloid Classifications

3 Physicochemical Properties

4 Category : Alkaloids

1 – Introduction :

Alkaloids are naturally occurring chemical compounds containing

basic nitrogen atoms . The name derives from the word alkaline and

was used to describe any nitrogen - containing base. Alkaloids are

produced by a large variety of organisms, including bacteria, fungi,

plants, and animals and are part of the group of natural products (also

called secondary metabolites ) . Many alkaloids can be purified from

crude extracts by acid - base extraction. Many alkaloids are toxic to

other organisms. They often have pharmacological effects and are

used as medications, as recreational drugs, or in entheogenic rituals.

Examples are the local anesthetic and stimulant cocaine, the stimulant

caffeine, nicotine, the analgesic morphine, or the antimalarial drug

quinine. Some alkaloids have a bitter taste .

Caffeine

http://en.wikipedia.org/wiki/Ephedrinehttp://en.wikipedia.org/wiki/Alkaloid#Alkaloid_classificationshttp://en.wikipedia.org/wiki/Alkaloid#Physicochemical_propertieshttp://en.wikipedia.org/wiki/Chemical_compoundhttp://en.wikipedia.org/wiki/Base_(chemistry)http://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Alkalinehttp://en.wikipedia.org/wiki/Bacteriahttp://en.wikipedia.org/wiki/Fungushttp://en.wikipedia.org/wiki/Planthttp://en.wikipedia.org/wiki/Animalhttp://en.wikipedia.org/wiki/Natural_productshttp://en.wikipedia.org/wiki/Secondary_metabolitehttp://en.wikipedia.org/wiki/Acid-base_extractionhttp://en.wikipedia.org/wiki/Toxicityhttp://en.wikipedia.org/wiki/Pharmacologyhttp://en.wikipedia.org/wiki/Medicationhttp://en.wikipedia.org/wiki/Recreational_drughttp://en.wikipedia.org/wiki/Entheogenichttp://en.wikipedia.org/wiki/Local_anesthetichttp://en.wikipedia.org/wiki/Stimulanthttp://en.wikipedia.org/wiki/Cocainehttp://en.wikipedia.org/wiki/Caffeinehttp://en.wikipedia.org/wiki/Nicotinehttp://en.wikipedia.org/wiki/Analgesichttp://en.wikipedia.org/wiki/Morphinehttp://en.wikipedia.org/wiki/Antimalarial_drughttp://en.wikipedia.org/wiki/Quininehttp://en.wikipedia.org/wiki/Bitter_(taste)#Bitternesshttp://en.wikipedia.org/wiki/Caffeine

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2 - Alkaloid classifications :

The classification of the alkaloids is complex and may be guided

by a set of rules that take into account the structure and other chemical

features of the alkaloid molecule, its biological origin, as well as the

biogenetic origin where known.[2][3]

For example, where the

biosynthesis pathway of an alkaloid is unknown, it may be grouped

based on structural similarities with known compounds, including

non-nitrogenous compounds, or by the organism (s) from which the

alkaloid was isolated .

Pyridine group :

piperine , coniine , trigonelline , arecoline , arecaidine , guvacine,

cytisine , lobeline , nicotine , anabasine , sparteine , pelletierine .

Pyrrolidine group : hygrine , cuscohygrine , nicotine .

Tropane group : atropine , cocaine , ecgonine , scopolamine , catuabine .

Indolizidine group : senecionine , swainsonine .

Quinoline group : quinine , quinidine , dihydroquinine, dihydroquinidine , strychnine ,

brucine , veratrine , cevadine .

Isoquinoline group : opium alkaloids ( papaverine , narcotine , narceine ) , pancratistatin ,

sanguinarine , hydrastine , berberine , emetine , berbamine ,

oxyacanthine .

Phenanthrene alkaloids : opium alkaloids ( morphine , codeine , thebaine , oripavine )

Phenethylamine group : mescaline , ephedrine , dopamine .

http://en.wikipedia.org/wiki/Chemical_structurehttp://en.wikipedia.org/wiki/Biosynthesishttp://en.wikipedia.org/wiki/Alkaloid#cite_note-Rogers.26Wink-1http://en.wikipedia.org/wiki/Alkaloid#cite_note-Rogers.26Wink-1http://en.wikipedia.org/wiki/Pyridinehttp://en.wikipedia.org/wiki/Piperinehttp://en.wikipedia.org/wiki/Coniinehttp://en.wikipedia.org/wiki/Trigonellinehttp://en.wikipedia.org/wiki/Arecolinehttp://en.wikipedia.org/w/index.php?title=Arecaidine&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Guvacine&action=edit&redlink=1http://en.wikipedia.org/wiki/Cytisinehttp://en.wikipedia.org/wiki/Lobelinehttp://en.wikipedia.org/wiki/Nicotinehttp://en.wikipedia.org/wiki/Anabasinehttp://en.wikipedia.org/wiki/Sparteinehttp://en.wikipedia.org/w/index.php?title=Pelletierine&action=edit&redlink=1http://en.wikipedia.org/wiki/Pyrrolidinehttp://en.wikipedia.org/wiki/Hygrinehttp://en.wikipedia.org/wiki/Cuscohygrinehttp://en.wikipedia.org/wiki/Nicotinehttp://en.wikipedia.org/wiki/Tropanehttp://en.wikipedia.org/wiki/Atropinehttp://en.wikipedia.org/wiki/Cocainehttp://en.wikipedia.org/wiki/Ecgoninehttp://en.wikipedia.org/wiki/Scopolaminehttp://en.wikipedia.org/wiki/Catuabinehttp://en.wikipedia.org/w/index.php?title=Indolizidine&action=edit&redlink=1http://en.wikipedia.org/wiki/Senecioninehttp://en.wikipedia.org/wiki/Swainsoninehttp://en.wikipedia.org/wiki/Quinolinehttp://en.wikipedia.org/wiki/Quininehttp://en.wikipedia.org/wiki/Quinidinehttp://en.wikipedia.org/wiki/Dihydroquininehttp://en.wikipedia.org/wiki/Dihydroquinidinehttp://en.wikipedia.org/wiki/Strychninehttp://en.wikipedia.org/wiki/Brucinehttp://en.wikipedia.org/wiki/Veratrinehttp://en.wikipedia.org/w/index.php?title=Cevadine&action=edit&redlink=1http://en.wikipedia.org/wiki/Isoquinolinehttp://en.wikipedia.org/wiki/Opiumhttp://en.wikipedia.org/wiki/Papaverinehttp://en.wikipedia.org/wiki/Narcotinehttp://en.wikipedia.org/w/index.php?title=Narceine&action=edit&redlink=1http://en.wikipedia.org/wiki/Pancratistatinhttp://en.wikipedia.org/wiki/Sanguinarinehttp://en.wikipedia.org/wiki/Hydrastinehttp://en.wikipedia.org/wiki/Berberinehttp://en.wikipedia.org/wiki/Emetinehttp://en.wikipedia.org/wiki/Phenanthrenehttp://en.wikipedia.org/wiki/Morphinehttp://en.wikipedia.org/wiki/Codeinehttp://en.wikipedia.org/wiki/Thebainehttp://en.wikipedia.org/wiki/Oripavinehttp://en.wikipedia.org/wiki/Phenethylaminehttp://en.wikipedia.org/wiki/Mescalinehttp://en.wikipedia.org/wiki/Ephedrinehttp://en.wikipedia.org/wiki/Dopamine

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Indole group :

Tryptamines : serotonin , bufotenine , psilocybin

Ergolines : ergine , ergotamine , lysergic acid

Beta - carbolines : harmine , harmaline , tetra hydro harmine

Yohimbans : reserpine, yohimbine .

Vinca alkaloids : vinblastine, vincristine .

Kratom) alkaloids : mitragynine , 7- hydroxy mitragynine .

Tabernanthe iboga : ibogaine , voacangine , coronaridine .

Strychnos nux-vomica : strychnine , brucine .

Purine group : Xanthines , caffeine , theobromine , theophylline .

Terpenoid group : Aconitum alkaloids : aconitine .

Steroid alkaloids : ( containing a steroid skeleton in a nitrogen

containing structure) :

Solanum alkaloids ( e.g. potato and tomato ) : ( solanidine , solanine ,

chaconine ) .

Veratrum alkaloids : ( veratramine , cyclo pamine , cycloposine ,

jervine , muldamine ) ..

Fire Salamander alkaloids : ( samandarin ) .

thers : conessine .

Quaternary ammonium compounds : muscarine , choline , neurine .

Miscellaneous : capsaicin , cynarin , phytolaccine , phytolaccotoxin .

3 - Physicochemical properties :

Low - molecular weight alkaloids without hydrogen bond donors

such as hydroxy groups are often liquid at room temperature ,

examples are nicotine , sparteine , coniine , and phenethylamine .

The basicity of alkaloids depends on the lone pairs of electrons on

their nitrogen atoms. As organic bases, alkaloids form salts with

mineral acids such as hydrochloric acid and sulfuric acid and organic

acids such as tartaric acid or maleic acid. These salts are usually more

water-soluble than their free base form .

http://en.wikipedia.org/wiki/Indolehttp://en.wikipedia.org/wiki/Tryptaminehttp://en.wikipedia.org/wiki/Serotoninhttp://en.wikipedia.org/wiki/Bufoteninehttp://en.wikipedia.org/wiki/Psilocybinhttp://en.wikipedia.org/wiki/Ergolinehttp://en.wikipedia.org/wiki/Erginehttp://en.wikipedia.org/wiki/Ergotaminehttp://en.wikipedia.org/wiki/Lysergic_acidhttp://en.wikipedia.org/wiki/Beta-carbolinehttp://en.wikipedia.org/wiki/Harminehttp://en.wikipedia.org/wiki/Harmala_alkaloidhttp://en.wikipedia.org/wiki/Tetrahydroharminehttp://en.wikipedia.org/wiki/Reserpinehttp://en.wikipedia.org/wiki/Yohimbinehttp://en.wikipedia.org/wiki/Catharanthus#Vinca_alkaloidshttp://en.wikipedia.org/wiki/Vinblastinehttp://en.wikipedia.org/wiki/Vincristinehttp://en.wikipedia.org/wiki/Kratomhttp://en.wikipedia.org/wiki/Mitragyninehttp://en.wikipedia.org/wiki/7-hydroxymitragyninehttp://en.wikipedia.org/wiki/Tabernanthe_ibogahttp://en.wikipedia.org/wiki/Ibogainehttp://en.wikipedia.org/wiki/Voacanginehttp://en.wikipedia.org/w/index.php?title=Coronaridine&action=edit&redlink=1http://en.wikipedia.org/wiki/Strychnos_nux-vomicahttp://en.wikipedia.org/wiki/Strychninehttp://en.wikipedia.org/wiki/Brucinehttp://en.wikipedia.org/wiki/Purinehttp://en.wikipedia.org/wiki/Xanthinehttp://en.wikipedia.org/wiki/Caffeinehttp://en.wikipedia.org/wiki/Theobrominehttp://en.wikipedia.org/wiki/Theophyllinehttp://en.wikipedia.org/wiki/Terpenoidhttp://en.wikipedia.org/wiki/Aconitumhttp://en.wikipedia.org/wiki/Aconitinehttp://en.wikipedia.org/wiki/Steroidhttp://en.wikipedia.org/wiki/Solanumhttp://en.wikipedia.org/wiki/Potatohttp://en.wikipedia.org/wiki/Tomatohttp://en.wikipedia.org/w/index.php?title=Solanidine&action=edit&redlink=1http://en.wikipedia.org/wiki/Solaninehttp://en.wikipedia.org/wiki/Chaconinehttp://en.wikipedia.org/wiki/Veratrumhttp://en.wikipedia.org/w/index.php?title=Veratramine&action=edit&redlink=1http://en.wikipedia.org/wiki/Cyclopaminehttp://en.wikipedia.org/w/index.php?title=Cycloposine&action=edit&redlink=1http://en.wikipedia.org/wiki/Jervinehttp://en.wikipedia.org/w/index.php?title=Muldamine&action=edit&redlink=1http://en.wikipedia.org/wiki/Fire_Salamanderhttp://en.wikipedia.org/wiki/Samandarinhttp://en.wikipedia.org/wiki/Conessinehttp://en.wikipedia.org/wiki/Ammoniumhttp://en.wikipedia.org/wiki/Muscarinehttp://en.wikipedia.org/wiki/Cholinehttp://en.wikipedia.org/wiki/Neurinehttp://en.wikipedia.org/wiki/Capsaicinhttp://en.wikipedia.org/w/index.php?title=Cynarin&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Phytolaccine&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Phytolaccotoxin&action=edit&redlink=1http://en.wikipedia.org/wiki/Hydrogen_bondhttp://en.wikipedia.org/wiki/Hydroxy_grouphttp://en.wikipedia.org/wiki/Nicotinehttp://en.wikipedia.org/wiki/Sparteinehttp://en.wikipedia.org/wiki/Coniinehttp://en.wikipedia.org/wiki/Phenethylaminehttp://en.wikipedia.org/wiki/Lone_pairhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Mineral_acidhttp://en.wikipedia.org/wiki/Hydrochloric_acidhttp://en.wikipedia.org/wiki/Sulfuric_acidhttp://en.wikipedia.org/wiki/Organic_acidhttp://en.wikipedia.org/wiki/Organic_acidhttp://en.wikipedia.org/wiki/Tartaric_acidhttp://en.wikipedia.org/wiki/Maleic_acidhttp://en.wikipedia.org/wiki/Solubilityhttp://en.wikipedia.org/wiki/Free_base

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4 - Category : Alkaloids :

An alkaloid is a naturally occurring nitrogenous organic molecule

that has a pharmacological effect on humans and other animals. The

name derives from the word alkaline; originally, the term was used to

describe any nitrogen - containing base (an amine in modern terms).

Alkaloids are found in plants (e.g., in potatoes and tomatoes), animals

(e.g., in shellfish) and fungi (e.g., in mushrooms), and can be extracted

from their sources by treatment with acids ( usually hydrochloric acid

or sulfuric acid, though organic acids such as maleic acid and citric

acid are sometimes used ) .

A : Acetylpsilocin . Aconitine . Ageliferin . Ajmalan . Ajmaline .

Akuammine . Allopumiliotoxin . Allopumiliotoxin 267A . Anabasine .

Anatoxin - a . Apomorphine . Aporphine

B : Batrachotoxin . Benzyl isoquinoline . Berberine . Brucine .

Bulbocapnine

C : Calligonine . Camptothecin . Carpaine . Castanospermine .

Cathinone . Chaconine . Chavicine . Chelerythrine . Cinchonidine .

Cinchonine . Colchicine . Conessine . Conhydrine . Coniine .

Coptisine . Coramsine . Cordycepin . Cryogenine . Cuscohygrine .

Cylindrospermopsin . Cytisine .

D : Dehydro emetine . Delphinine . Demecolcine . Dihydro

ergocornine . Dihydro ergocristine . Dihydro quinidine . Dihydro

quinine . Docetaxel

E : Eletefine . Emetine . Epibatidine . Ergine E cont . Ergoline .

Ethocybin .

G : Glaucine . Glycoalkaloid .

H : Harmine . Hasubanan . Hasubanonine . Himbacine . Histrio

nicotoxin . Hodgkinsine . Horsfiline . Huperzine A . Hydrastine .

Hydrastinine . Hygrine .

I : Imidazole . Isovaleramide

http://en.wikipedia.org/wiki/Moleculehttp://en.wikipedia.org/wiki/Pharmacologyhttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/Animalhttp://en.wikipedia.org/wiki/Alkalihttp://en.wikipedia.org/wiki/Base_(chemistry)http://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Planthttp://en.wikipedia.org/wiki/Potatohttp://en.wikipedia.org/wiki/Tomatohttp://en.wikipedia.org/wiki/Shellfishhttp://en.wikipedia.org/wiki/Fungushttp://en.wikipedia.org/wiki/Mushroomhttp://en.wikipedia.org/wiki/Acidhttp://en.wikipedia.org/wiki/Hydrochloric_acidhttp://en.wikipedia.org/wiki/Sulfuric_acidhttp://en.wikipedia.org/wiki/Maleic_acidhttp://en.wikipedia.org/wiki/Citric_acidhttp://en.wikipedia.org/wiki/Citric_acidhttp://en.wikipedia.org/wiki/O-Acetylpsilocinhttp://en.wikipedia.org/wiki/Aconitinehttp://en.wikipedia.org/wiki/Ageliferinhttp://en.wikipedia.org/wiki/Ajmalanhttp://en.wikipedia.org/wiki/Ajmalinehttp://en.wikipedia.org/wiki/Akuamminehttp://en.wikipedia.org/wiki/Allopumiliotoxinhttp://en.wikipedia.org/wiki/Allopumiliotoxin_267Ahttp://en.wikipedia.org/wiki/Anabasinehttp://en.wikipedia.org/wiki/Anatoxin-ahttp://en.wikipedia.org/wiki/Apomorphine_(data_page)http://en.wikipedia.org/wiki/Aporphinehttp://en.wikipedia.org/wiki/Batrachotoxinhttp://en.wikipedia.org/wiki/Benzylisoquinolinehttp://en.wikipedia.org/wiki/Berberinehttp://en.wikipedia.org/wiki/Brucinehttp://en.wikipedia.org/wiki/Bulbocapninehttp://en.wikipedia.org/wiki/Calligoninehttp://en.wikipedia.org/wiki/Camptothecinhttp://en.wikipedia.org/wiki/Carpainehttp://en.wikipedia.org/wiki/Castanosperminehttp://en.wikipedia.org/wiki/Cathinonehttp://en.wikipedia.org/wiki/Chaconinehttp://en.wikipedia.org/wiki/Chavicinehttp://en.wikipedia.org/wiki/Chelerythrinehttp://en.wikipedia.org/wiki/Cinchonidinehttp://en.wikipedia.org/wiki/Cinchoninehttp://en.wikipedia.org/wiki/Colchicinehttp://en.wikipedia.org/wiki/Conessinehttp://en.wikipedia.org/wiki/Conhydrinehttp://en.wikipedia.org/wiki/Coniinehttp://en.wikipedia.org/wiki/Coptisinehttp://en.wikipedia.org/wiki/Coramsinehttp://en.wikipedia.org/wiki/Cordycepinhttp://en.wikipedia.org/wiki/Cryogeninehttp://en.wikipedia.org/wiki/Cuscohygrinehttp://en.wikipedia.org/wiki/Cylindrospermopsinhttp://en.wikipedia.org/wiki/Cytisinehttp://en.wikipedia.org/wiki/Dehydroemetinehttp://en.wikipedia.org/wiki/Delphininehttp://en.wikipedia.org/wiki/Demecolcinehttp://en.wikipedia.org/wiki/Dihydroergocorninehttp://en.wikipedia.org/wiki/Dihydroergocorninehttp://en.wikipedia.org/wiki/Dihydroergocristinehttp://en.wikipedia.org/wiki/Dihydroquinidinehttp://en.wikipedia.org/wiki/Dihydroquininehttp://en.wikipedia.org/wiki/Dihydroquininehttp://en.wikipedia.org/wiki/Docetaxelhttp://en.wikipedia.org/wiki/Eletefinehttp://en.wikipedia.org/wiki/Emetinehttp://en.wikipedia.org/wiki/Epibatidinehttp://en.wikipedia.org/wiki/Erginehttp://en.wikipedia.org/wiki/Ergolinehttp://en.wikipedia.org/wiki/Ethocybinhttp://en.wikipedia.org/wiki/Glaucinehttp://en.wikipedia.org/wiki/Glycoalkaloidhttp://en.wikipedia.org/wiki/Harminehttp://en.wikipedia.org/wiki/Hasubananhttp://en.wikipedia.org/wiki/Hasubanoninehttp://en.wikipedia.org/wiki/Himbacinehttp://en.wikipedia.org/wiki/Histrionicotoxinhttp://en.wikipedia.org/wiki/Histrionicotoxinhttp://en.wikipedia.org/wiki/Hodgkinsinehttp://en.wikipedia.org/wiki/Horsfilinehttp://en.wikipedia.org/wiki/Huperzine_Ahttp://en.wikipedia.org/wiki/Hydrastinehttp://en.wikipedia.org/wiki/Hydrastininehttp://en.wikipedia.org/wiki/Hygrinehttp://en.wikipedia.org/wiki/Imidazolehttp://en.wikipedia.org/wiki/Isovaleramide

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L : Lennoxamine . Leonurine . Lobeline . Loline alkaloids .

Lupinine . Lycorine . Lysergic acid hydroxy ethylamide .

M : Methcathinone . Methoxy methyl enedioxy amphetamine .

Methoxy coronaridine . 1-Methyl - 2,3,4,9 – tetra hydro -1H – pyrido -

3,4 – b - indole . Methyl benzo dioxolyl butanamine . N –Methyl

coniine . Methyllycaconitine . Methylone .

N : Nantenine . Narcotoline . Neurine . Nicotine .

Norzoanthamine .

O : Orellanine

P : Paclitaxel . Pancratistatin . Pericine . Phenyl propanol amine .

Phenyl tropane . Physostigmine . Piperine . Prajmaline . Pseudo

aconitine . Pseudo pelletierine . Pukateine P cont . Pumiliotoxin .

Pumiliotoxin 251D . Pyrrolizidine alkaloid .

R : Rhynchophylline . Rodiasine . Ryanodine .

S : Samandaridine . Samandarin . Sanguinarine . Saxitoxin .

Scoulerine . Senecionine . Sinomenine . Solamargine . Solanine .

Solanocapsine . Solasodamine . Solasodine . Solasonine .

Solauricidine . Solauricine . Solenopsin . Sparteine . Spirotryprostatin.

Staurosporine . Stepholidine . Strychnine . Swainsonine .

T : Tetra hydro harman . Tetra hydro palmatine . Thebaine . Tri

gonelline . Tri methoxy amphetamine . Tropane . Tropane alkaloid .

Tropinone . Tryptoline . Tubocurarine

V : Veracevine . Veratridine . Vinblastine . Vinburnine .

Vincristine . Vindesine . Vinflunine . Vinorelbine . Voacangine .

Y : Yuremamine

http://en.wikipedia.org/wiki/Lennoxaminehttp://en.wikipedia.org/wiki/Leonurinehttp://en.wikipedia.org/wiki/Lobelinehttp://en.wikipedia.org/wiki/Loline_alkaloidshttp://en.wikipedia.org/wiki/Lupininehttp://en.wikipedia.org/wiki/Lycorinehttp://en.wikipedia.org/wiki/Lysergic_acid_hydroxyethylamidehttp://en.wikipedia.org/wiki/Methcathinonehttp://en.wikipedia.org/wiki/Methoxymethylenedioxyamphetaminehttp://en.wikipedia.org/wiki/18-Methoxycoronaridinehttp://en.wikipedia.org/wiki/18-Methoxycoronaridinehttp://en.wikipedia.org/wiki/(1S)-1-Methyl-2,3,4,9-tetrahydro-1H-pyrido-3,4-b-indolehttp://en.wikipedia.org/wiki/(1S)-1-Methyl-2,3,4,9-tetrahydro-1H-pyrido-3,4-b-indolehttp://en.wikipedia.org/wiki/Methylbenzodioxolylbutanaminehttp://en.wikipedia.org/wiki/N-Methylconiinehttp://en.wikipedia.org/wiki/N-Methylconiinehttp://en.wikipedia.org/wiki/Methyllycaconitinehttp://en.wikipedia.org/wiki/Methylonehttp://en.wikipedia.org/wiki/Nanteninehttp://en.wikipedia.org/wiki/Narcotolinehttp://en.wikipedia.org/wiki/Neurinehttp://en.wikipedia.org/wiki/Nicotinehttp://en.wikipedia.org/wiki/Norzoanthaminehttp://en.wikipedia.org/wiki/Orellaninehttp://en.wikipedia.org/wiki/Paclitaxelhttp://en.wikipedia.org/wiki/Pancratistatinhttp://en.wikipedia.org/wiki/Pericinehttp://en.wikipedia.org/wiki/Phenylpropanolaminehttp://en.wikipedia.org/wiki/Phenyltropanehttp://en.wikipedia.org/wiki/Physostigminehttp://en.wikipedia.org/wiki/Piperinehttp://en.wikipedia.org/wiki/Prajmalinehttp://en.wikipedia.org/wiki/Pseudaconitinehttp://en.wikipedia.org/wiki/Pseudaconitinehttp://en.wikipedia.org/wiki/Pseudopelletierinehttp://en.wikipedia.org/wiki/Pukateinehttp://en.wikipedia.org/wiki/Pumiliotoxinhttp://en.wikipedia.org/wiki/Pumiliotoxin_251Dhttp://en.wikipedia.org/wiki/Pyrrolizidine_alkaloidhttp://en.wikipedia.org/wiki/Rhynchophyllinehttp://en.wikipedia.org/wiki/Rodiasinehttp://en.wikipedia.org/wiki/Ryanodinehttp://en.wikipedia.org/wiki/Samandaridinehttp://en.wikipedia.org/wiki/Samandarinhttp://en.wikipedia.org/wiki/Sanguinarinehttp://en.wikipedia.org/wiki/Saxitoxinhttp://en.wikipedia.org/wiki/Scoulerinehttp://en.wikipedia.org/wiki/Senecioninehttp://en.wikipedia.org/wiki/Sinomeninehttp://en.wikipedia.org/wiki/Solamarginehttp://en.wikipedia.org/wiki/Solaninehttp://en.wikipedia.org/wiki/Solanocapsinehttp://en.wikipedia.org/wiki/Solasodaminehttp://en.wikipedia.org/wiki/Solasodinehttp://en.wikipedia.org/wiki/Solasoninehttp://en.wikipedia.org/wiki/Solauricidinehttp://en.wikipedia.org/wiki/Solauricinehttp://en.wikipedia.org/wiki/Solenopsinhttp://en.wikipedia.org/wiki/Sparteinehttp://en.wikipedia.org/wiki/Spirotryprostatin_Ahttp://en.wikipedia.org/wiki/Staurosporinehttp://en.wikipedia.org/wiki/Stepholidinehttp://en.wikipedia.org/wiki/Strychninehttp://en.wikipedia.org/wiki/Swainsoninehttp://en.wikipedia.org/wiki/Tetrahydroharmanhttp://en.wikipedia.org/wiki/Tetrahydropalmatinehttp://en.wikipedia.org/wiki/Thebainehttp://en.wikipedia.org/wiki/Trigonellinehttp://en.wikipedia.org/wiki/Trigonellinehttp://en.wikipedia.org/wiki/Trimethoxyamphetaminehttp://en.wikipedia.org/wiki/Tropanehttp://en.wikipedia.org/wiki/Tropane_alkaloidhttp://en.wikipedia.org/wiki/Tropinonehttp://en.wikipedia.org/wiki/Tryptolinehttp://en.wikipedia.org/wiki/Tubocurarinehttp://en.wikipedia.org/wiki/Veracevinehttp://en.wikipedia.org/wiki/Veratridinehttp://en.wikipedia.org/wiki/Vinblastinehttp://en.wikipedia.org/wiki/Vinburninehttp://en.wikipedia.org/wiki/Vincristinehttp://en.wikipedia.org/wiki/Vindesinehttp://en.wikipedia.org/wiki/Vinfluninehttp://en.wikipedia.org/wiki/Vinorelbinehttp://en.wikipedia.org/wiki/Voacanginehttp://en.wikipedia.org/wiki/Yuremamine

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Atropine

Contents :

1 Introduction

2 Physiological effects and uses

o 2.1 Ophthalmic use

o 2.2 Resuscitation

o 2.3 Secretions and bronchoconstriction

o 2.4 Treatment for organophosphate poisoning

o 2.5 Optical penalization

o 2.6 Side - effects and overdose

3 Chemistry and pharmacology

4 History

5 Natural sources

1 – Introduction :

Atropine is a tropane alkaloid extracted from deadly nightshade (

Atropa belladonna ) , jimsonweed ( Datura stramonium ) , mandrake (

Mandragora officinarum ) and other plants of the family Solanaceae .

It is a secondary metabolite of these plants and serves as a drug with a

wide variety of effects. It is a competitive antagonist for the

muscarinic acetylcholine receptor. It is classified as an anti cholinergic

drug. Being potentially deadly, it derives its name from Atropos, one

of the three Fates who, according to Greek mythology, chose how a

person was to die. Atropine is a core medicine in the World Health

Organization's "Essential Drugs List", which is a list of minimum

medical needs for a basic health care system .

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13

Systematic (IUPAC) name

( 8 – methyl – 8 – azabicyclo [ 3.2.1 ] oct – 3 – yl ) 3 –

hydroxyl – 2 – phenyl propanoate

Formula C17H23NO3

Mol Mass 289

Pharmacokinetic data

Bioavailability 25 %

Metabolism 50 % hydrolyzed to tropine and tropic acid

Half life 2 hours

Excretion 50 % excreted unchanged in urine

2 - Physiological effects and uses

Atropine increases firing of the sinoatrial node (SA) and

conduction through the atrioventricular node (AV) of the heart,

opposes the actions of the vagus nerve , blocks acetylcholine receptor

sites, and decreases bronchial secretions.

In general, atropine lowers the parasympathetic activity of all

muscles and glands regulated by the parasympathetic nervous system.

This occurs because atropine is a competitive antagonist of the

muscarinic acetylcholine receptors ( Acetylcholine is the main

neurotransmitter used by the parasympathetic nervous system ) .

Therefore, it may cause swallowing difficulties and reduced secretions

2 -1 : Ophthalmic use

Topical atropine is used as a cyclo plegic, to temporarily paralyze

the accommodation reflex, and as a mydriatic, to dilate the pupils.

Atropine degrades slowly, typically wearing off in 7 to 14 days, so it

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14

is generally used as a therapeutic mydriatic , whereas tropicamide ( a

shorter - acting cholinergic antagonist ) or phenyl ephrine (an α-

adrenergic agonist) is preferred as an aid to ophthalmic examination.

Atropine induces mydriasis by blocking contraction of the circular

pupillary sphincter muscle, which is normally stimulated by

acetylcholine release, thereby allowing the radial pupillary dilator

muscle to contract and dilate the pupil. Atropine induces cycloplegia

by paralyzing the ciliary muscles, whose action inhibits

accommodation to allow accurate refraction in children, helps to

relieve pain associated with iridocyclitis, and treats ciliary block

(malignant) glaucoma. Atropine is contraindicated in patients pre-

disposed to narrow angle glaucoma . Atropine can be given to patients

who have direct globe trauma .

2 – 2 : Resuscitation

Injections of atropine are used in the treatment of bradycardia (an

extremely low heart rate), asystole and pulseless electrical activity

(PEA) in cardiac arrest. This works because the main action of the

vagus nerve of the parasympathetic system on the heart is to decrease

heart rate. Atropine blocks this action and, therefore, may speed up the

heart rate. The usual dosage of atropine in bradyasystolic arrest is 0.5

to 1 mg IV push every three to five minutes, up to a maximum dose of

0.04 mg/kg. For symptomatic bradycardia, the usual dosage is 0.5 to

1.0 mg IV push, may repeat every 3 to 5 minutes up to a maximum

dose of 3.0 mg .

Atropine is also useful in treating second-degree heart block

Mobitz Type 1 (Wenckebach block), and also third-degree heart block

with a high Purkinje or AV-nodal escape rhythm. It is usually not

effective in second - degree heart block Mobitz type 2, and in third-

degree heart block with a low Purkinje or ventricular escape rhythm.

Atropine is contraindicated in ischemia-induced conduction block,

because the drug increases oxygen demand of the AV nodal tissue,

thereby aggravating ischemia and the resulting heart block.

One of the main actions of the parasympathetic nervous system is

to stimulate the M2 muscarinic receptor in the heart, but atropine

inhibits this action.

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15

2 – 3 : Secretions and broncho constriction

Atropine's actions on the parasympathetic nervous system inhibits

salivary, sweat, and mucus glands. This can be useful in treating

hyperhidrosis, and can prevent the death rattle of dying patients. Even

though atropine has not been officially indicated for either of these

purposes by the FDA, it has been used by physicians for these

purposes .

2 – 4 : Treatment for organophosphate poisoning

Atropine is not an actual antidote for organophosphate poisoning.

However, by blocking the action of acetylcholine at muscarinic

receptors, atropine also serves as a treatment for poisoning by

organophosphate insecticides and nerve gases, such as Tabun (GA),

Sarin (GB), Soman (GD) and VX. Troops that are likely to be attacked

with chemical weapons often carry autoinjectors with atropine and

obidoxime, which can be quickly injected into the thigh. Atropine is

often used in conjunction with Pralidoxime chloride.

Atropine is given as a treatment for SLUDGE (Salivation,

Lacrimation, Urination, Diaphoresis, Gastrointestinal motility,

Emesis) symptoms caused by organophosphate poisoning .

Some of the nerve agents attack and destroy acetyl cholin

esterase , so the action of acetylcholine becomes prolonged. Therefore

atropine can be used to reduce the effect of acetylcholine .

2 – 5 : Optical penalization :

In refractive and accommodative amblyopia , when occlusion is not

appropriate sometimes atropine is given to induce blur in the good eye

2 – 6 : Side - effects and overdose

Adverse reactions to atropine include ventricular fibrillation,

supra ventricular or ventricular tachycardia, dizziness, nausea, blurred

vision, loss of balance, dilated pupils, photophobia, and, possibly,

notably in the elderly, extreme confusion, extreme dissociative

hallucinations, and excitation. These latter effects are because atropine

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16

is able to cross the blood - brain barrier. Because of the hallucinogenic

properties, some have used the drug recreationally, though this is

potentially dangerous and often unpleasant.

In overdoses, atropine is poisonous. Atropine is sometimes added

to other potentially addictive drugs, particularly anti-diarrhea opioid

drugs such as diphenoxylate or difenoxin, wherein the secretion-

reducing effects of the atropine can also aid the anti-diarrhea effects.

Although atropine treats bradycardia ( slow heart rate ) in

emergency settings, it can cause paradoxical heart rate slowing when

given at very low doses, presumably as a result of central action in the

CNS. The antidote to atropine is physostigmine or pilocarpine .

A common mnemonic used to describe the physiologic

manifestations of atropine overdose is: "hot as a hare, blind as a bat,

dry as a bone, red as a beet, and mad as a hatter".[6]

These associations

reflect the specific changes of warm, dry skin from decreased

sweating, blurry vision , decreased sweating / lacrimation ,

vasodilation, and central nervous system effects on muscarinic

receptors, type 4 and 5 . This set of symptoms is known as anti

cholinergic toxidrome , and may also be caused by other drugs with

anti cholinergic effects, such as diphenhy dramine , phenothiazine

antipsychotics and benztropine .

3 - Chemistry and pharmacology

Atropine is a racemic mixture of D - hyoscyamine and L -

hyoscyamine , with most of its physiological effects due to L –

hyoscyamine . Its pharmacological effects are due to binding to

muscarinic acetylcholine receptors. It is an antimuscarinic agent.The

most common atropine compound used in medicine is atropine sulfate

( C17H23NO3 )2 · H2SO4 ·H2O, the full chemical name is 1α H , 5α H –

Tropan – 3 - α ol (±) – tropate (ester) , sulfate mono hydrate .

4 - History

Mandragora (mandrake) was described by Theophrastus in the

fourth century B.C. for treatment of wounds, gout, and sleeplessness,

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17

and as a love potion. By the first century A.D. Dioscorides recognized

wine of mandrake as an anaesthetic for treatment of pain or

sleeplessness, to be given prior to surgery or cautery . The use of

Solanaceae containing tropane alkaloids for anesthesia, often in

combination with opium, persisted throughout the Roman and Islamic

Empires and continued in Europe until superseded by the use of ether,

chloroform, and other modern anesthetics.

Atropine extracts from the Egyptian henbane were used by

Cleopatra in the last century B.C. to dilate her pupils, in the hope that

she would appear more alluring. In the Renaissance, women used the

juice of the berries of Atropa belladonna to enlarge the pupils of their

eyes, for cosmetic reasons; " bella donna " is Italian for "beautiful

lady".[8]

This practice resumed briefly in the late nineteenth - and early

twentieth - century in Paris .

The mydriatic effects of atropine were studied among others by

the German chemist Friedrich Ferdinand Runge (1795–1867). In

1831, the pharmacist Mein succeeded the pure crystalline isolation of

atropine. The substance was first synthesized by German chemist

Richard Willstätter in 1901.

Atropinic shock therapy, also known as atropinic coma therapy, is

an old and rarely - used method. It consists of induction of atropinic

coma by rapid intravenous infusion of atropine. Atropinic shock

treatment is considered safe with careful monitoring and preparation,

but it entails prolonged coma (between four and five hours), and it has

many unpleasant side-effects, such as blurred vision .

5 - Natural sources

Atropine is found in many members of the Solanaceae family.

The most commonly-found sources are Atropa belladonna, Datura

inoxia, D. metel, and D. stramonium. Other sources include members

of the Brugmansia and Hyoscyamus genera . The Nicotiana genus

( including the tobacco plant, N. tabacum ) is also found in the

Solanaceae family, but these plants do not contain atropine or other

tropane alkaloids .

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18

Caffeine

Contents :

1 Introduction

2 Occurrence

3 History

4 Synthesis and properties

5 Pharmacology

o 5.1 Metabolism and half-life

o 5.2 Mechanism of action

o 5.3 Effects when taken in moderation

o 5.4 Tolerance and withdrawal

o 5.5 Overuse

5.5.1 Caffeine intoxication

5.5.2 Anxiety and sleep disorders

o 5.6 Effects on memory and learning

o 5.7 Effects on the heart

o 5.8 Effects on children

o 5.9 Caffeine intake during pregnancy

o 5.10 Genetics and caffeine metabolism

o 5.11 Intraocular Pressure and caffeine

6 Decaffeination

o 6.1 Water extraction

o 6.2 Supercritical carbon dioxide extraction

o 6.3 Extraction by organic solvents

7 Religion

1 – Introduction :

Caffeine is a bitter , white crystalline xanthine alkaloid that is a

psychoactive stimulant drug . Caffeine was discovered by a German

chemist , Friedrich Ferdinand Runge , in 1819 . He coined the term

kaffein , a chemical compound in coffee , which in English became

caffeine . Caffeine is also part of the chemical mixtures and insoluble

complexes guaranine found in guarana , mateine found in mate , and

theine found in non - herbal tea ; all of which contain additional

alkaloids such as the cardiac stimulants theophylline and theobromine,

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19

and often other chemicals such as polyphenols which can form

insoluble complexes with caffeine .

Caffeine is found in varying quantities in the beans , leaves , and

fruit of some plants , where it acts as a natural pesticide that paralyzes

and kills certain insects feeding on the plants . It is most commonly

consumed by humans in infusions extracted from the cherries of the

coffee plant and the leaves of the tea bush , as well as from various

foods and drinks containing products derived from the kola nut . Other

sources include yerba mate , guarana berries, and the Yaupon Holly .

In humans , caffeine is a central nervous system ( CNS ) stimulant

having the effect of temporarily warding off drowsiness and restoring

alertness . Beverages containing caffeine , such as coffee , tea , soft

drinks , and energy drinks enjoy great popularity . Caffeine is the

world's most widely consumed psychoactive substance , but unlike

many other psychoactive substances it is legal and unregulated in

nearly all jurisdictions . In North America , 90 % of adults consume

caffeine daily . The U.S . Food and Drug Administration lists caffeine

as a " multiple purpose generally recognized as safe food substance ".

Caffeine has diuretic properties, at least when administered in

sufficient doses to subjects who do not have a tolerance for it .

Regular users , however , develop a strong tolerance to this effect ,

and studies have generally failed to support the common notion that

ordinary consumption of caffeinated beverages contributes

significantly to dehydration .

Other Names

1,3,7- Tri methyl xanthine ,

Tri methyl xanthine ,

Theine ,

Methyl theo bromine

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20

Molecular Formula C8 H10 N4 O2

Molar Mass 194 g / mol

Appearance Odorless , white needles or powder

Density 1.23 g /cm3 , solid

Melting Point 227 – 228 °C ( anhydrous) ,

234 – 235 °C ( monohydrate )

Boiling Point 178 °C subl .

Solubility in Water

2.17 g / 100 ml ( 25 °C )

18.0 g / 100 ml ( 80 °C )

67.0 g / 100 ml ( 100 °C )

Acidity ( pKa ) − 0.13 – 1.22

Dipole Moment 3.64 D ( calculated )

EU classification Harmful ( Xn )

LD50 192 mg / kg ( rat , oral )

2 - Occurrence :

Roasted coffee beans, a common source of caffeine

Caffeine is found in many plant species , where it acts as a natural

pesticide , with high caffeine levels being reported in seedlings that

are still developing foliages, but are lacking mechanical protection ;

caffeine paralyzes and kills certain insects feeding upon the plant .

High caffeine levels have also been found in the surrounding soil of

coffee bean seedlings. It is therefore understood that caffeine has a

natural function as both a natural pesticide and as an inhibitor of seed

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21

germination of other nearby coffee seedlings thus giving it a better

chance of survival .

The most commonly used sources of caffeine are coffee, tea , and

to a lesser extent cacao . Less commonly used sources of caffeine

include the yerba maté and guarana plants,[15]

which are sometimes

used in the preparation of teas and energy drinks . Two of caffeine's

alternative names, mateine and guaranine , are derived from the

names of these plants . Some yerba mate enthusiasts assert that

mateine is a stereoisomer of caffeine , which would make it a different

substance altogether . This is not true because caffeine is an achiral

molecule , and therefore has no enantiomers ; nor does it have other

stereoisomers . The disparity in experience and effects between the

various natural caffeine sources could be due to the fact that plant

sources of caffeine also contain widely varying mixtures of other

xanthine alkaloids , including the cardiac stimulants theophylline and

theobromine and other substances such as polyphenols which can

form insoluble complexes with caffeine .

One of the world's primary sources of caffeine is the coffee bean

( which is the seed of the coffee plant ) , from which coffee is brewed .

Caffeine content in coffee varies widely depending on the type of

coffee bean and the method of preparation used ; even beans within a

given bush can show variations in concentration . In general, one

serving of coffee ranges from 40 milligrams , for a single shot ( 30

milliliters ) of arabica - variety espresso, to about 100 milligrams for

a cup ( 120 milliliters ) of drip coffee . Generally , dark - roast coffee

has less caffeine than lighter roasts because the roasting process

reduces the bean's caffeine content . Arabica coffee normally contains

less caffeine than the robusta variety . Coffee also contains trace

amounts of theophylline , but no theobromine .

Tea is another common source of caffeine. Although tea contains

more caffeine than coffee , a typical serving contains much less , as

tea is normally brewed much weaker. Besides strength of the brew ,

growing conditions , processing techniques and other variables also

affect caffeine content . Certain types of tea may contain somewhat

more caffeine than other teas . Tea contains small amounts of

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22

theobromine and slightly higher levels of theophylline than coffee.

Preparation and many other factors have a significant impact on tea,

and color is a very poor indicator of caffeine content . Teas like the

pale Japanese green tea gyokuro , for example , contain far more

caffeine than much darker teas like lapsang souchong , which has very

little .

Caffeine content of select common food and drugs :

Product Serving size

Caffeine

per serving

(mg)

Caffeine per

litre (mg)

Caffeine tablet

( regular strength ) 1 tablet 100 —

Caffeine tablet

( extra strength ) 1 tablet 200 —

Excedrin tablet 1 tablet 65 —

Hershey's Special

Dark ( 45 % cacao

content )

1 bar (43 g; 1.5 oz) 31 —

Hershey's Milk

Chocolate ( 11 %

cacao content )

1 bar (43 g; 1.5 oz) 10 —

Percolated coffee 207 mL ( 7 U.S. fl oz) 80 – 135 386 - 652

Drip coffee 207 mL ( 7 U.S. fl oz) 115 – 175 555–845

Coffee,decaffeinated 207 mL ( 7 U.S. fl oz) 5 - 15 24 - 72

Coffee , espresso 44–60 mL ( 2 U.S. fl oz ) 100 1691- 2254

Coffee , Starbucks ( Tall 12 U.S. fl oz ) 240 650 - 700

Black tea 177 mL (6 U.S. fl oz) 50 282

Green tea 177 mL ( 6 U.S. fl oz ) 30 169

Coca - Cola Classic 355 mL ( 12 U.S. fl oz ) 34 96

Caffeine is also a common ingredient of soft drinks such as cola ,

originally prepared from kola nuts. Soft drinks typically contain about

10 to 50 milligrams of caffeine per serving. By contrast , energy

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23

drinks such as Red Bull can start at 80 milligrams of caffeine per

serving . The caffeine in these drinks either originates from the

ingredients used or is an additive derived from the product of

decaffeination or from chemical synthesis. Guarana, a prime

ingredient of energy drinks , contains large amounts of caffeine with

small amounts of theobromine and theophylline in a naturally

occurring slow-release excipient .

Chocolate derived from cocoa contains a small amount of

caffeine. The weak stimulant effect of chocolate may be due to a

combination of theobromine and theophylline as well as caffeine . A

typical 28 - gram serving of a milk chocolate bar has about as much

caffeine as a cup of decaffeinated coffee .

In recent years various manufacturers have begun putting caffeine

into shower products such as shampoo and soap , claiming that

caffeine can be absorbed through the skin . However, the effectiveness

of such products has not been proven, and they are likely to have little

stimulatory effect on the central nervous system because caffeine is

not readily absorbed through the skin .

Various manufacturers market caffeine tablets , claiming that

using caffeine of pharmaceutical quality improves mental alertness .

These effects have been borne out by research that shows that caffeine

use ( whether in tablet form or not ) results in decreased fatigue and

increased attentiveness . These tablets are commonly used by students

studying for their exams and by people who work or drive for long

hours .

3 - History :

Humans have consumed caffeine since the Stone Age . Early

peoples found that chewing the seeds , bark , or leaves of certain

plants had the effects of easing fatigue , stimulating awareness , and

elevating one's mood . Only much later was it found that the effect of

caffeine was increased by steeping such plants in hot water. Many

cultures have legends that attribute the discovery of such plants to

people living many thousands of years ago .

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24

A coffeehouse in Palestine , circa 1900

According to one popular Chinese legend, the Emperor of China

Shennong , reputed to have reigned in about 3000 BC , accidentally

discovered that when some leaves fell into boiling water , a fragrant

and restorative drink resulted . Shennong is also mentioned in Lu Yu's

Cha Jing , a famous early work on the subject of tea . The history of

coffee has been recorded as far back as the ninth century . During that

time, coffee beans were available only in their native habitat , Ethiopia

A popular legend traces its discovery to a goatherder named Kaldi ,

who apparently observed goats that became elated and sleepless at

night after grazing on coffee shrubs and , upon trying the berries that

the goats had been eating, experienced the same vitality. The earliest

literary mention of coffee may be a reference to Bunchum in the

works of the 9th century Persian physician al - Razi. In 1587 , Malaye

Jaziri compiled a work tracing the history and legal controversies of

coffee, entitled " Undat al safwa fi hill al - qahwa ". In this work ,

Jaziri recorded that one Sheikh , Jamal – al - Din al – Dhabhani , mufti

of Aden , was the first to adopt the use of coffee in 1454 , and that in

the 15th century the Sufis of Yemen routinely used coffee to stay

awake during prayers .

Towards the close of the 16th century , the use of coffee was

recorded by a European resident in Egypt , and about this time it came

into general use in the Near East . The appreciation of coffee as a

beverage in Europe, where it was first known as "Arabian wine," dates

from the 17th century . During this time " coffee houses " were

established , the first being opened in Constantinople and Venice . In

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25

Britain , the first coffee houses were opened in London in 1652 , at St

Michael's Alley , Cornhill . They soon became popular throughout

Western Europe, and played a significant role in social relations in the

17th and 18th centuries .

The kola nut , like the coffee berry and tea leaf , appears to have

ancient origins . It is chewed in many West African cultures,

individually or in a social setting, to restore vitality and ease hunger

pangs . In 1911 , kola became the focus of one of the earliest

documented health scares when the US government seized 40 barrels

and 20 kegs of Coca - Cola syrup in Chattanooga , Tennessee , lleging

that the caffeine in its drink was " injurious to health ".[34]

On March

13 , 1911 , the government initiated The United States v. Forty Barrels

and Twenty Kegs of Coca - Cola, hoping to force Coca - Cola to

remove caffeine from its formula by making claims, such as that the

excessive use of Coca - Cola at one girls' school led to " wild

nocturnal freaks , violations of college rules and female proprieties,

and even immoralities." Although the judge ruled in favor of Coca-

Cola, two bills were introduced to the U.S. House of Representatives

in 1912 to amend the Pure Food and Drug Act, adding caffeine to the

list of " habit - forming " and "deleterious" substances which must be

listed on a product's label .

The earliest evidence of cocoa use comes from residue found in

an ancient Mayan pot dated to 600 BC. In the New World, chocolate

was consumed in a bitter and spicy drink called xocoatl, often

seasoned with vanilla, chile pepper, and achiote. Xocoatl was believed

to fight fatigue , a belief that is probably attributable to the

theobromine and caffeine content . Chocolate was an important luxury

good throughout pre - Columbian Mesoamerica, and cocoa beans were

often used as currency .

Xocoatl was introduced to Europe by the Spaniards and became a

popular beverage by 1700 . They also introduced the cacao tree into

the West Indies and the Philippines. It was used in alchemical

processes, where it was known as Black Bean .

The leaves and stems of the Yaupon Holly (Ilex vomitoria) were

used by Native Americans to brew a tea called Asi or the Black Drink

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26

the use of which among Native American groups archaeologists have

demonstrated to stretch back far into antiquity, possibly dating to Late

Archaic times.

4 - Synthesis and properties :

In 1819, the German chemist Friedrich Ferdinand Runge isolated

relatively pure caffeine for the first time. According to Runge , he did

this at the behest of Johann Wolfgang von Goethe . In 1827 , Oudry

isolated " theine " from tea, but it was later proved by Mulder and

Jobat that theine was the same as caffeine . The structure of caffeine

was elucidated near the end of the 19th century by Hermann Emil

Fischer , who was also the first to achieve its total synthesis . This was

part of the work for which Fischer was awarded the Nobel Prize in

1902 . The nitrogen atoms are all essentially planar ( in sp 2

orbital

hybridisation ) , resulting in the caffeine molecule having aromatic

character . Being readily available as a byproduct of decaffeination,

caffeine is not usually synthesized . If desired, it may be synthesized

from dimethylurea and malonic acid .

5 - Pharmacology :

Global consumption of caffeine has been estimated at

120,000 tonnes per year , making it the world's most popular

psychoactive substance. This number equates to one serving of a

caffeine beverage for every person, per day . Caffeine is a central

nervous system and metabolic stimulant , and is used both

recreationally and medically to reduce physical fatigue and restore

mental alertness when unusual weakness or drowsiness occurs.

Caffeine and other methylxanthine derivatives are also used on

newborns to treat apnea and correct irregular heartbeats. Caffeine

stimulates the central nervous system first at the higher levels,

resulting in increased alertness and wakefulness, faster and clearer

flow of thought , increased focus, and better general body

coordination, and later at the spinal cord level at higher doses.[28]

Once

inside the body, it has a complex chemistry, and acts through several

mechanisms as described below.

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27

5 – 1 : Metabolism and half-life

Caffeine is metabolized in the liver into three primary metabolites :

paraxanthine ( 84 % ) , theobromine ( 12 % ) , and theophylline (4 %).

Caffeine from coffee or other beverages is absorbed by the

stomach and small intestine within 45 minutes of ingestion and then

distributed throughout all tissues of the body.[41]

It is eliminated by

first-order kinetics.[42]

Caffeine can also be ingested rectally,

evidenced by the formulation of suppositories of ergotamine tartrate

and caffeine ( for the relief of migraine ) and chlorobutanol and

caffeine ( for the treatment of hyperemesis ) .

The half-life of caffeine — the time required for the body to

eliminate one-half of the total amount of caffeine — varies widely

among individuals according to such factors as age, liver function,

pregnancy, some concurrent medications, and the level of enzymes in

the liver needed for caffeine metabolism. In healthy adults, caffeine's

half-life is approximately 4.9 hours. In women taking oral

contraceptives this is increased to 5 – 10 hours , and in pregnant

women the half-life is roughly 9 –1 1 hours . Caffeine can accumulate

in individuals with severe liver disease , increasing its half-life up to

96 hours . In infants and young children, the half - life may be longer

than in adults; half-life in a newborn baby may be as long as 30 hours.

Other factors such as smoking can shorten caffeine's half - life .

Fluvoxamine reduced the apparent oral clearance of caffeine by

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28

91.3 % , and prolonged its elimination half - life by 11.4 - fold ( from

4.9 hours to 56 hours ) .

Caffeine is metabolized in the liver by the cytochrome P450

oxidase enzyme system ( specifically , the 1A2 isozyme ) into three

metabolic dimethylxanthines , which each have their own effects on

the body :

Paraxanthine ( 84 % ) : Has the effect of increasing

lipolysis, leading to elevated glycerol and free fatty acid levels in

the blood plasma.

Theobromine (12 % ) : Dilates blood vessels and increases

urine volume. Theobromine is also the principal alkaloid in

cocoa, and therefore chocolate.

Theophylline ( 4 % ) : Relaxes smooth muscles of the

bronchi, and is used to treat asthma. The therapeutic dose of

theophylline, however, is many times greater than the levels

attained from caffeine metabolism.

Each of these metabolites is further metabolized and then

excreted in the urine.

5- 2 : Mechanism of action

Caffeine's principal mode of action is as an antagonist of

adenosine receptors in the brain .

Like alcohol and nicotine, caffeine readily crosses the blood–

brain barrier that separates the bloodstream from the interior of the

brain. Once in the brain, the principal mode of action is as an

antagonist of adenosine receptors . The caffeine molecule is

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29

structurally similar to adenosine, and binds to adenosine receptors on

the surface of cells without activating them ( an " antagonist "

mechanism of action ). Therefore, caffeine acts as a competitive

inhibitor .

Adenosine is found in every part of the body, because it plays a

role in the fundamental ATP - related energy metabolism, but it has

special functions in the brain. There is a great deal of evidence that

concentrations of brain adenosine are increased by various types of

metabolic stress including anoxia and ischemia. The evidence also

indicates that brain adenosine acts to protect the brain by suppressing

neural activity and also by increasing blood flow through A2A and

A2B receptors located on vascular smooth muscle . By counteracting

adenosine, caffeine reduces resting cerebral blood flow between 22%

and 30%.[53]

Caffeine also has a generally disinhibitory effect on

neural activity. It has not been shown, however, how these effects

cause increases in arousal and alertness.

Adenosine is released in the brain through a complex

mechanism.[52]

There is evidence that adenosine functions as a

synaptically released neurotransmitter in some cases, but stress-related

adenosine increases appear to be produced mainly by extracellular

metabolism of ATP. It is not likely that adenosine is the primary

neurotransmitter for any group of neurons, but rather that it is released

together with other transmitters by a number of neuron types. Unlike

most neurotransmitters, adenosine does not seem to be packaged into

vesicles that are released in a voltage - controlled manner, but the

possibility of such a mechanism has not been completely ruled out.

Several classes of adenosine receptors have been described, with

different anatomical distributions. A1 receptors are widely distributed,

and act to inhibit calcium uptake. A2A receptors are heavily

concentrated in the basal ganglia, an area that plays a critical role in

behavior control, but can be found in other parts of the brain as well,

in lower densities. There is evidence that A 2A receptors interact with

the dopamine system , which is involved in reward and arousal. ( A2A

receptors can also be found on arterial walls and blood cell

membranes ) .

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Beyond its general neuroprotective effects, there are reasons to

believe that adenosine may be more specifically involved in control of

the sleep-wake cycle. Robert McCarley and his colleagues have

argued that accumulation of adenosine may be a primary cause of the

sensation of sleepiness that follows prolonged mental activity, and that

the effects may be mediated both by inhibition of wake-promoting

neurons via A1 receptors, and activation of sleep-promoting neurons

via indirect effects on A2A receptors.[54]

More recent studies have

provided additional evidence for the importance of A2A , but not A1 ,

receptors . Some of the secondary effects of caffeine are probably

caused by actions unrelated to adenosine. Caffeine is known to be a

competitive inhibitor of the enzyme cAMP - phosphodiesterase

( cAMP – PDE ) , which converts cyclic AMP (cAMP) in cells to its

noncyclic form, thus allowing cAMP to build up in cells. Cyclic AMP

participates in activation of protein kinase A (PKA) to begin the

phosphorylation of specific enzymes used in glucose synthesis. By

blocking its removal caffeine intensifies and prolongs the effects of

epinephrine and epinephrine-like drugs such as amphetamine,

methamphetamine, or methylphenidate. Increased concentrations of

cAMP in parietal cells causes an increased activation of protein kinase

A (PKA) which in turn increases activation of H+ / K+ ATPase ,

resulting finally in increased gastric acid secretion by the cell. Cyclic

AMP also increases the activity of the funny current, which directly

increases heart rate. Caffeine is also a structural analogue of

strychnine and like it ( though much less potent ) a competitive

antagonist at ionotropic glycine receptors .

Metabolites of caffeine also contribute to caffeine's effects.

Paraxanthine is responsible for an increase in the lipolysis process,

which releases glycerol and fatty acids into the blood to be used as a

source of fuel by the muscles. Theobromine is a vasodilator that

increases the amount of oxygen and nutrient flow to the brain and

muscles. Theophylline acts as a smooth muscle relaxant that chiefly

affects bronchioles and acts as a chronotrope and inotrope that

increases heart rate and efficiency .

Caffeine has a significant effect on spiders , which is reflected in

the construction of their webs.

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31

5 – 3 : Effects when taken in moderation :

Over view of the more common side effects of caffeine, possibly

appearing even at levels below overdose .

The precise amount of caffeine necessary to produce effects

varies from person to person depending on body size and degree of

tolerance to caffeine. It takes less than an hour for caffeine to begin

affecting the body and a mild dose wears off in three to four hours.[28]

Consumption of caffeine does not eliminate the need for sleep, it only

temporarily reduces the sensation of being tired throughout the day. In

general, 25 to 50 milligrams of caffeine is sufficient for most people

to report increased alertness and arousal as well as subjectively lower

levels of fatigue.

With these effects, caffeine is an ergogenic, increasing a person's

capability for mental or physical labor. A study conducted in 1979

showed a 7 % increase in distance cycled over a period of two hours

in subjects who consumed caffeine compared to control subjects.[60]

Other studies attained much more dramatic results; one particular

study of trained runners showed a 44 % increase in "race-pace"

endurance, as well as a 51 % increase in cycling endurance, after a

dosage of 9 milligrams of caffeine per kilogram of body weight.[61]

Additional studies have reported similar effects. Another study found

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32

5.5 milligrams of caffeine per kilogram of body mass resulted in

subjects cycling 29 % longer during high intensity circuits .

Caffeine citrate has proven to be of short and long term benefit in

treating the breathing disorders of apnea of prematurity and

bronchopulmonary dysplasia in premature infants . The only short

term risk associated with caffeine citrate treatment is a temporary

reduction in weight gain during the therapy , and longer term studies

(18 to 21 months ) have shown lasting benefits of treatment of

premature infants with caffeine .

Caffeine relaxes the internal anal sphincter muscles and thus

should be avoided by those with fecal incontinence .

While relatively safe for humans, caffeine is considerably more

toxic to some other animals such as dogs, horses, and parrots due to a

much poorer ability to metabolize this compound. Caffeine has also a

pronounced effect on mollusks and various insects as well as spiders.

5 – 4 : Tolerance and with drawal :

Because caffeine is primarily an antagonist of the central nervous

system's receptors for the neurotransmitter adenosine, the bodies of

individuals who regularly consume caffeine adapt to the continual

presence of the drug by substantially increasing the number of

adenosine receptors in the central nervous system. This increase in the

number of the adenosine receptors makes the body much more

sensitive to adenosine, with two primary consequences . First, the

stimulatory effects of caffeine are substantially reduced, a

phenomenon known as a tolerance adaptation. Second, because these

adaptive responses to caffeine make individuals much more sensitive

to adenosine, a reduction in caffeine intake will effectively increase

the normal physiological effects of adenosine, resulting in unwelcome

withdrawal symptoms in tolerant users .

Other research questions the idea that up-regulation of adenosine

receptors is responsible for tolerance to the locomotor stimulant

effects of caffeine, noting, among other things, that this tolerance is

insurmountable by higher doses of caffeine (it should be surmountable

http://en.wikipedia.org/wiki/Caffeine_citratehttp://en.wikipedia.org/wiki/Apnea_of_prematurityhttp://en.wikipedia.org/wiki/Premature_birthhttp://en.wikipedia.org/wiki/Sphincter_ani_internus_musclehttp://en.wikipedia.org/wiki/Fecal_incontinencehttp://en.wikipedia.org/wiki/Spiderhttp://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Neurotransmitterhttp://en.wikipedia.org/wiki/Adenosinehttp://en.wikipedia.org/wiki/Adenosine_receptorhttp://en.wikipedia.org/wiki/Drug_tolerance