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HISTORY OF PHARMACOLOGY

INTRODUCTION
Etymologically, pharmacology is the science of drugs

(Greek pharmakos, medicine or drug; and logos,

study).
Pharmacology is one of the cornerstones of the drug

discovery process.
The medicinal chemist may create the candidate

compound, but the pharmacologist is the one who


tests it for physiologic activity.
A promising compound is investigated by many other

An acquaintance with the history of a subject frequently reveals the true nature of the subject. Tracing the growth of pharmacology, then, from its earliest beginnings will give us a sharper

perspective of the scope of the field and a clearer

understanding of what distinguishes pharmacology


today as an orderly science in its own right.

In the words of the Nobel laureate Albert Szent-

Gyrgyi,

If we want to see ahead we must

THE BEGINNINGS
The use of medicinals by humans is as old as the

human race itself, since the need to find measures to combat sickness was as important to survival as the need for food and shelter.

Ancient civilizations used mixtures of magic, religion

and crude drugs to treat diseases. Drugs were often


thought to be magical in their actions .

The drugs of antiquity mainly came from plant

sources or were obtained from animal parts or fluids.

The use of alcohol and opium to ease pain, of

cinchona bark (the source of quinine) to treat malaria and of ipecac for amebic dysentery can be cited as examples of early therapeutic success despite ignorance of the causes of these ailments.

Some

of the failures can also be called valuable

discoveries, since drugs like curare, known only as fatal

poisons by primitive cultures in various regions of the


world, became valuable therapeutic agents when used in proper amounts.

Thus the accumulation of this primitive medical lore and its

dissemination and use by midwives, priests, witch doctors and other practitioners were the beginnings of materia

PHARMACOLOGY AND TOXICOLOGY IN ANCIENT INDIA


The worlds oldest known pharmacological or therapeutic

writings come from India and China.


The early humans used plants, plant products, minerals,

animal products, etc. against diseases. They believed that any patient can be cured with the help of herbs and other natural things present in ones surroundings.
This knowledge about medicine was gathered empirically

through trial and error and compiled verbally and passed on orally from generation to generation.

Much later, some of this information was codified into

treatise form in the Rgveda, Yajurveda, Charak Samhita, Sushrut Samhita, Astanganighantu, etc. Out of these

treatises

Rigveda(3000

B.C.)

is

the

most

ancient

document with some portions about medical knowledge.

Although there are medical descriptions in Rigveda, it was

Charaka, a renowned ancient Indian physician, and later Sushruta and Vagbhata, who described various medicinal preparations included in Ayurveda, the science of life.

Initially, these consisted mostly of nonpoisonous herbal

Charaka described about 300 herbal drugs and classified

them according to their effects, mostly on symptoms into 50groups.


The materia medica of Ayurveda is very comprehensive

and includes most of drugs from vegetable origins. Susruta has described the properties of 760 drugs of the vegetable kingdom. It also included animal-origin substances, minerals, etc.
In the Ayurvedic tradition, the literature on pharmacology

(Dravyaguna) is generally known as Nighantu.

The original Ayurvedic materia medica was later

superseded to some extent by the alchemic or chemical substances at about the beginning of

Christian era.

CHINA
The

great

herbal

or

Chinese

materia

medica

PAN TSAO was probably written in 2735 B.C. and

contained many plant and metallic preparations and a


few animal products including toads eyelids,

elephants and tigers bones, horns, fins, etc.,.


China's Shen Nong's "The Divine Farmer's Herb-Root

Classic" contains 365 medicine compounds made from minerals, plants and animals. Shen Nong personally tested the properties of hundreds of medical herbs he

EGYPT AND BABYLONIA


The Egyptians are to be credited with the oldest known

records of medicine, even though the medical systems of Sumaria, Babylonia and India are probably of equal antiquity.

The most ancient of the records devoted entirely to

medicine is the Papyrus of Smith (ca. 1600 BCE). It


clearly indicates that the Egyptians had developed a codified and conventionalized form of therapy for a great

The Ebers Papyrus (1550 BCE), the largest of the

Egyptian medical papyri, lists more than 700 remedies and

describes in detail the procedures for their preparation and


administration for specific ailments. There is reference to liver as a remedy for anemia and to modern drugs, such as castor oil and opium.

The

Babylonian clay tablet (700 B.C.) mentions about

GREECE
Hippocrates (460B.C.-377 B.C.). The Father of Medicine

was the first to attempt to separate the practice of medicine from religion and superstition , developed his pledge of proper conduct for doctors.

Hippocrates believed that the body has ample natural

resources for recuperation and that the role of the physician was to remove or reduce the impediments to this

natural defense.

He relied mainly upon fresh air, good food, purgatives and

Pedanius Dioscorides (40 - 90-AD)

Pedanius Dioscorides, a

Greek physician,

personally researched each plant and its uses.


About

65

AD,

he

wrote

De

Materia

Medica, "Regarding Medical Matters", on the

"preparation, properties, and testing of drugs."

INFLUENCE OF PARACELSUS
Aureolus Paracelsus (14931541), whose real name was

Philippus Theophrastus Bombastus von Hohenheim, has

been called the Grandfather of Pharmacology.

Paracelsus believed that mans body is composed of

chemicals and advocated the theory that illness is a disturbance of the chemical constituents of the body.

Popularized the use of chemical tinctures and extracts and

compounded laudanum, the tincture of opium.

Opposed the indiscriminate use of drug mixtures derived

from the plant and animal world, recognizing that any


useful substance which they contained was probably diluted to ineffective concentrations by their inert

ingredients.
Stressed the curative powers of single agents, particularly

inorganic materials, such as the use of mercury to treat syphilis.


He recognized the relationship between the amount of a

drug administered and the beneficial or harmful effects produced, for he wrote: All things are poisons, for there

THE RISE OF PHARMACOLOGY


The

experimental methods and work of Paracelsus

certainly forecast the modern approach to pharmacology. This noteworthy event followed close on the heels of William Harveys (15781657) explanation of the circulation of the blood.
Harveys Exercitatio anatomica de motu cordis et sanguinis

in animalibus in 1628 signaled the beginning of the

scientific study of drug action. It opened the way for


administering drugs in a new mannerby the intravenous routeand thus made it possible to demonstrate temporal

A great chemist and physicist, Robert Boyle, who

apparently was among the first to use this new route to investigate drug action in animals.
About the year 1660, Boyle and an associate,

Timothy

Clarke,

showed

by

well-controlled

pharmacologic experiments that drugs are active


when administered by vein.
They also indirectly proved that these drugs, when

taken by mouth, could produce the same effects only after being absorbed into the circulation.

The work of the Swiss physician John Jacob Wepfer (16201695)

was

the

first

critical

publication

of

careful

and

large-scale

pharmacologic experiments designed and carried out to determine the

toxicity of drugs and poisons in animals.

Felix Fontana (17201805), following the example set by Wepfer, also

performed thousands of experiments on the toxicity of various crude


drugs. His results suggested to him that a crude drug contains an active principle which preferentially acts upon one or more discrete

parts of the organism to produce a characteristic effect.

Thus

Fontanas

premise

was

preamble

to

the

pioneering

The work of a young pharmacists apprentice, Peter John

Andrew Daries, in the late eighteenth century, was of

equal or perhaps greater importance to pharmacology than


that of Fontana.

Through his astute deductions, he anticipated by many

years the establishment of one of the fundamental

pharmacologic
relationship

principles,
between

namely,
the

that

there
of a

is

amount

drug

administered and the magnitude of the biologic

Early in the development of pharmacologic techniques, it

was found that an isolated organ or tissue remained functional for several hours in a bath containing a physiologic solution of salts through which oxygen was bubbled.
Henrick Magnus (18021870) first applied this method to a

strip of small intestine.


Jean-Franois

Heymans

(1904)

worked

with

the

The Influence of Advances in Physiology and Chemistry


To

pioneers

like

Magendie

and

Bernard,

modern

pharmacology owes a debt equal to that owed by modern


physiology.
The methods of physiologic experimentation which they

established and employed were as fundamental and essential to understanding normal physiologic processes

as they were to understanding the dynamic actions of


chemicals on biologic processes and materials.
They provided the means for discovering what drugs do in

The revolutionizing changes that occurred in chemistry

almost simultaneously with those in physiology were of equal importance to the subsequent rapid rise of

pharmacology.
The German apothecary Frederick W.A.Sertrner (1783

1841) in 1806 isolated a white crystalline substance,


morphine, from opium. This first isolation of an active principle of a medicinal plant stimulated much enthusiastic research on other botanical drugs.
After

the

momentous

discovery

of

Sertrner,

pharmaceutical chemistry rapidly took its place as an

With

new isolation procedures, many natural drugs

became available for investigation and use, and with the invention of chemical syntheses, many derivatives of natural products were made.
Synthetic organic chemistry was born in 1828, when

Friedrich

Wohler

synthesized

urea

from

inorganic

substances.
The advances in organic chemistry also resulted in the

Pharmacology as a Separate Discipline


Once chemistry had provided the pure chemicals, and

physiology the experimental methods with which to


determine their biologic activity, pharmacologists had the implements they needed to advance their science to a discipline in its own right.

From this time on, new developments in all aspects of

pharmacology followed one another in quick succession.

Nevertheless, pharmacology is held to have emerged as

a separate science only when the first university chair was established. According to Walter Sneader, this

occurred in 1847, when Rudolf Buchheim was appointed


professor of pharmacology at the University of Dorpat in Estonia (then a part of Russia).

Buchheim is credited with turning the purely descriptive

and empirical study of medicines into an experimental science.

Pharmacology as a Profession
Buchheim and Schmiedeberg are important figures in

pharmacology not only for their contributions to its

substantive content but also for the stature to which they


raised the discipline.
Buchheim was the first professor of pharmacology as well

as the founder of the first laboratory devoted exclusively to experimental pharmacology as an independent part of

physiology.
Oswald Schmiedeberg, as professor of pharmacology at

Strasburg, Germany, continued this transformation of the

The Modern Era


Together

with

the

tremendous

achievements

in

the

advancement of pharmacology to the status of a science, the

nineteenth and early part of the twentieth centuries witnessed


dramatic discoveries of new pharmacologic agents.
Ehrlichs work showing that drugs can be developed which are

capable of destroying invading organisms without disabling the


host ushered in the era of chemotherapy.
The discovery of insulin by Banting and Best in 1921 led to

dramatic success in the treatment of diabetes; it also focused attention on the therapeutic use of normally occurring substances as replacement for what the body is unable to

All these events and more formed the basis for the rational

therapy of disease.
And the growth of the pharmaceutical industry, with its

extensive programs of research and development, ensured the availability of an ever-increasing number of new drugs

for the treatment and prevention of more and more


diseases.

GREAT

SCIENTISTS & THEIR CONTRIBUTION S

Paracelsus(14931541)
Paracelsus (Philippus Theophrastus Bombastus

von Hohenheim), who united chemistry with medicine; he discarded the ancient theories of the causes of disease and advocated the belief that illness is a derangement of body chemistry to be treated by simple chemical therapeutic

William Harvey
William

Harvey

(15781657),

who

explained the circulation of the blood; this momentous discovery signaled the

beginning of the scientific study of the


medical sciences.

FRIEDRICH ALBRECHT KARL GREN(17601798)


German chemist and physician. Defined the term Pharmacology for the first

time in 1971.
Distinguished between 'pharmacology as the

science of the action of drugs' and 'materia medica as the description and collection of drugs'.

William Withering
William Withering (1741-1799) discovered digitalis.

Extract

of foxglove plant, used to treat dropsy

(congestive heart failure) in 1785. Contains digitoxin and digoxin; today called digitalis.

Franois Magendie(1783 1855)

Franois Magendie
Franois Magendie (17831855), who pioneered the

experimental approach to the study of pharmacology as well as physiology.


Studied the action of nux vomica (a strychnine-

containing plant drug) on dogs, and showed that the spinal cord was the site of its convulsant action.
Showed that the effect of drugs were the result of

actions within specific organs of the body.

Frederick W.A.Sertrner (17831841)


The German pharmacist who isolated the

first

alkaloid

from

opium

in

1805,

administered a very large dose (100 mg) to himself and three friends .
All experienced the symptoms of severe

opium poisoning for several days. The

Claude Bernard (18131878)

Claude Bernard (18131878),


A French Physiologist. First to demonstrate and explain how a drug produces its

action in the body.


Further expanded work of Francois Megendie.

In 1842, Claude Bernard discovered that the arrow poison

curare acts at the neuromuscular junction to interrupt the

stimulation of muscle by nerve impulses.


From this time on, the determination of the locus of action

of a drug became an essential part of the study of the drug.

James Blake (18151893)


First set forth the principles that drugs are

effective only after reaching a responsive tissue

and that there is a relationship between the


structure of drugs and the effects that they produce.

Friedrich Wohler
Synthetic organic chemistry was born in 1828, when

Friedrich Wohler synthesized urea from inorganic substances and thus demolished the vital force theory.

Rudolf Buchheim(1820 1879)

Rudolf Buchheim
The first professor of pharmacology as well as

founder of the first laboratory devoted exclusively to experimental pharmacology; he raised

pharmacology to a position of equal importance with other branches of medicine.


Advanced the thesis that drug activity could be

explained

on

the

basis

of

physicochemical

Oswald Schmiedeberg (18381921)

Oswald Schmiedeberg
The first great teacher of pharmacology; his textbook,

techniques and students set the pattern for the

worldwide development of pharmacology.


Schmiedeberg obtained his medical doctorate in 1866

with a thesis on the measurement of chloroform in


blood .
Added

the concept that drug activity is the

consequence of a dynamic equilibrium.


In 1878, he published a classic text, Outline of

Paul Ehrlich (18541915)

Paul Ehrlich
Ushered in the era of chemotherapy by showing

that chemicals can be made which are capable of destroying particular invading organisms.
Formulated the concept of receptors, i.e. that

part of a chemical component of living tissue with which a drug combines to produce its biologic effect.
In

1909 he and his student Sahachiro Hata developed Salvarsan, a treatment effective

John Jacob Abel (18571938)


An American Pharmacologist, ph.D from the

university of Michigan and trained under Schmiedeberg.


In the United States, the first chair in
1857- 1938

pharmacology Jacob Abel.


Also

was

established

at

the

University of Michigan in 1890 under John

k/a
on

FATHER

OF
of

AMERICAN
adrenaline,

PHARMACOLOGY.
Worked

purification

Gerhard Domagk (1895-1964)


German pathologist and bacteriologist.

Credited with the discovery of

Sulfonamidochrysoidine (KI-730) the first commercially available antibiotic (marketed under the brand name Prontosil).
He found the sulfonamide Prontosil to be effective

against streptococcus, and treated his own daughter with it, saving her the amputation of an arm.

Louis Lasagna (1923-2003 )

Louis Lasagna : Father of Clinical Pharmacology


Famous American Clinical Pharmacologist. Lasagna

joined

the

faculty

of

Johns

HopkinsUniversity in 1954, where he established the first ever clinical pharmacology department.
In 1964, Lasagna revised the Hippocratic Oath.
Conceptualize controlled clinical trials and the placebo

effect.
Lasagna's work led to the improvement of controlled

clinical trials to test drug effectiveness, and improved

CONTRIBUTIONS

OF INDIAN PHARMACOLOGI STS

Colonel Ram Nath Chopra (1882-1973)

Colonel Ram Nath Chopra


k/a FATHER OF INDIAN PHARMACOLOGY. Obtained MD degree from Cambridge University in 1908. Col.

R.N. his

Chopra mission of

s i n g l e - mindedly spearestablishing a place for

headed

pharmacology in the medical curriculum in India.


In 1921 : Appointed as the first professor of pharmacology

in newly

established

Calcutta School of

Tropical

Medicine and parallely headed the Department of pharmacology at Calcutta medical college .

He 1st introduced and done systematic study of

Rauwolfia serpentina .
Had a major contribution in establishing the 1st

National Drug Research Institute of India, Lucknow ( presently known as Central Drug Research Institute, CDRI).
He pioneered research on herbal drugs in

India.
Indian Posts & Telegraph department has

REFLECTIONS ON THE EVOLUTION OF PHARMACOLOGY IN INDIA DURING TWENTIETH CENTURY


A book Materia Medica of India and Therapeutics was

published in 1903 by RN Khory and NN Katrak.


B Mukherji collaborated with Chopra at STM (1928 -1937).

Later he established the Central Drug Research

Institute at Lucknow exclusively for pharmacological


research, standardization and toxicological studies of drugs.
He was its Director 1951-63 and has been a pioneer in

Indigenous Drug Research. Apart from several research

Professor

SW Hardikar took MD and MRCP from

Edinburgh and is the first Indian to work as University


Assistant in Department of Materia Medica at Edinburgh (1922-24).
Dr. UK Sheth(MD Gen. Medicine)- a Pioneer in India to

start a Clinical Pharmacology wing.

Pioneers of Pharmacology

Hippocrates: Father of Modern Medicine

Claude Bernard: Father of Modern Experimental

Pharmacology

Oswald

Schmiedberg:

Father

of

Modern

Pharmacology

Paul Ehrlich: Father of Modern Chemotherapy

John Jacob Abel: Father of American Pharmacology


Ram Nath Chopra: Father of Indian Pharmacology

Serendipity in Pharmacology
Penicillin by Alexander Fleming. He failed to disinfect

cultures of bacteria when leaving for his vacations, only to find them contaminated with Penicillium molds, which killed the bacteria.
5-fluorouracil's therapeutic action on actinic keratosis,

was initially investigated for its anti-cancer actions.


Minoxidil's action on baldness; originally it was an oral

agent for treating hypertension. It was observed that bald patients treated with it grew hair too.

Viagra (sildenafil citrate), an anti-impotence drug. It

was initially studied for use in hypertension and angina


pectoris. Phase I clinical trials under the direction of Ian Osterloh suggested that the drug had little effect on angina, but that it could induce marked penile erections.
The first anti-psychotic drug, chlorpromazine, was

discovered by French pharmacologist Henri Laborit.

He wanted to add an anti-histaminic to prevent surgical


shock and noticed that patients treated with it were unusually calm before the operation.

The psychedelic effects of LSD by Albert Hofmann, he

unintentionally absorbed a small amount of it upon investigating


its properties, and had the first acid trip in history, while cycling to his home in Switzerland; this is commemorated among LSD

users annually as Bicycle Day.


Mustine a derivative of mustard gas (a chemical weapon). In

1943, physicians noted that the white cell counts of US soldiers, accidentally exposed mustard gas shells were decreased, and mustard gas was investigated as a therapy for Hodgkin's lymphoma.
The anesthetic nitrous oxide (laughing gas). Its properties were

discovered when British chemist Humphry Davy tested the gas

on himself and some of his friends, and soon realised that

LIST OF SCIENTISTS WHO EXPERIMENTED ON THEMSELVES


Freidrich Serturner - Morphine Humphry Davy - Nitrous oxide Benjamin Ward Richardson Amyl Nitrate Enoch Hale Jr Castor oil J.E. Purkinje Digitalis toxicity P.J. Towry - Charcoal for strychnine and arsenic poisoning

A. Hoffman LSD
Smith & Prescott Curare Salk polio vaccine

CONCLUSION
As Albert Szent- Gyrgyi has stated:

The future is the continuum of the past, the


present being the dividing line between the two.

The progress made in the recent past, greater


than in all the years before, becomes our

REFERENCES
Satoskar RS, Bhandarkar SD, Rege NN. Section I. General

pharmacology. Pharmacology and Pharmacotherapeutics. 20th edition. India: Popular Prakashan; 2007. p. 1.
Curtis,

Sutter,

Walker,

Hoffman.

Chapter

1.

Integrated

Pharmacology. 2nd edition. China: elseveir Mosby; 2002. p.6-9.


D.P. Agrawal & Lalit Tiwari. Pharmacology and toxicology in

ancient India.
E. Muscholl. The evolution of experimental pharmacology as a

biological science: the pioneering work of Buchheim and

Schmiedeberg. British Journal of Pharmacology; 1995(116),

P.S.R.K.

HARANATH.

REFLECTIONS

ON

THE

EVOLUTION OF PHARMACOLOGY IN INDIA DURING TWENTIETH CENTURY. Indian Journal of Pharmacology 1999; 31: 1-13.
S.K. KULKARNI. EDUCATIONAL FORUM. Indian Journal

of Pharmacology 2003 ; 35 : 146 150.


Walsh

CT,

Schwartz

RD.

chapter

History

of

pharmacology. Levines Pharmacology Drug actions and reactions. 7th edition. UK: Taylor & Francis; 2005. p.1-16.
Stanley Scheindlin. A brief history of pharmacology.

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