History of pharmacology

& contributions of various

scientists in pharmacology
INTRODUCTION & HISTORICAL
DEVELOPMENT
SOME HISTORICAL LANDMARKS
GREAT SCIENTISTS & THEIR
CONTRIBUTIONS
PIONEERS OF PHARMACOLOGY
NOBEL LAUREATES IN PHARMACOLOGY
SERENDIPITY IN PHARMACOLOGY
A Brief History of Pharmacology
 Pharmacology is the science of drugs (Greek
pharmakos, medicine or drug; and logos, study).
 It is the study of substances that interact with living
systems through chemical processes, especially
through binding to regulatory molecules and activating
or inhibiting normal body processes.
 Knowledge of drugs and their use in disease is as old
as history of mankind.
 But as a science Pharmacology is quite a young one.
 The birth date of pharmacology is not as clear-cut.
A Brief History of Pharmacology
 Primitive men gathered the knowledge of healing and medicine by
observing the nature, noticing animals while ill and by personal
experiences after consuming certain herbs and berries as remedies.
 Hippocrates (460B.C.-377B.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,
 “I will use treatment to help the sick according to my ability and
judgment, but never with the view to injury and wrong doing…Into
whatsoever houses I enter, I will enter to help the sick”.
A Brief History of Pharmacology
 Ebers papyrus describes more than 700 drugs in extensive
pharmacopeia of that civilization. Included in this are: beer,
turpentine, berries, poppy, lead, salt and crushed precious stones
etc. (Egyptian remedies).
 Dhanvantari: an early Indian medical practitioner and one of the
world’s first surgeons, regarded as the source of Ayurveda. He
perfected many herbal based cures and natural remedies and was
credited with the discovery of the antiseptic properties
of turmeric and the preservative properties of salt which he
incorporated in his cures.
 Susruta Ancient Hindu Medical Text Describes 760 herbs.
 Charka Samhita describes more than 65O drugs of animal, plant and
mineral origins are used.
A Brief History of Pharmacology
 Paracelsus (1493-1541): pioneered the use of chemicals and
minerals (zinc) in medicine. Vigorously opposed polypharmacy, or
the prescription of multiple ingredients in a single medicine.
 Willow bark was used to treat fever and pains.
 Extract of foxglove plant, used to treat dropsy (congestive heart
failure) in 1785. Contains digitoxin and digoxin; today called digitalis.
William Withering (1741-1799) discovered digitalis.
 Synthetic organic chemistry was born in 1828, when Friedrich
Wohler synthesized urea from inorganic substances and thus
demolished the vital force theory.
Some Historical landmarks
 Morphine: Friedrich Serturner (1805)
 Atropine: Grieger & Hessie (1833)
 Histamine: Vogt (1907)
 Sulfanilamide: P. Gleno (1908)
 Oxytocin: Abel (1919)
 Insulin: Banting & Best (1922)
 Penicillins: A. Flemming (1928)
 Sulfonamides: Domagk (1932)
 Cortisone: Edward C.Kendall
 Streptomycin: Waksman (1944)
 Chloramphenicol: Bartz (1948)
 Tetracycline: Duggar (1948)
 Lithium: Cade (1950).
Pedanius Dioscorides, a Greek physician (40—90 AD)
 He 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."
 A five volume book on the uses of over 1,000 plants
and minerals.
 For nearly 1500 years, De Materia Medica was the
supreme authority on medicine and pharmacology in
western civilization.
FRANÇOIS MAGENDIE (1783 – 1855)
 A French physiologist, considered a pioneer of
experimental physiology.
 He is known for describing the foramen of Magendie.
 There is also a Magendie sign, a downward and
inward rotation of the eye due to a lesion in
the cerebellum.
 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.
 His work was presented to the Paris Academy in
1809.
FRANÇOIS MAGENDIE (1783 – 1855)
 Established the idea of experimental physiology (an
idea further popularized by Claude Bernard).
 He described in detail the effects of strychnine
injections on animal subjects and also proved that
the poison reached the animal's spinal cord by the
blood stream and not (as was then commonly
believed) by the lymphatic system.
 Because of such experiments, Magendie was able to
introduce into French medicine a variety of new
drugs, including morphine, codeine, quinine and,
strychnine.
Claude Bernard (1813-1878)
 A French Physiologist.
 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.
 Also k/a Father of Modern Experimental Medicine.
 Bernard's experiments changed medicine.
Claude Bernard Contributions
 The discovery of the role of the pancreatic secretion
in the digestion of fats (1848).
 The discovery of a new function of the liver--the
"internal secretion" of glucose into the blood (1848).
 The production of sugar by washed excised liver
(1855) and the isolation of glycogen (1857).
 The demonstration that curare specifically blocks
motor nerve endings (1856).
 He also established the existence of Vasomotor
system and observed Vasodilatation &
Vasoconstriction.
Rudolf Buccheim (1820—1879)
 Pharmacology was held to have emerged as a separate
science only when the first university chair was established.
 This occurred in 1847, when Rudolf Buchheim (a
German pharmacologist), was appointed professor of
Pharmacology at the University of Dorpat in Estonia.
 Today at the University of Giessen is the Rudolf Buchheim
Institute for Pharmacology.
 Lacking outside funding, Buchheim built the world’s 1st
pharmacology laboratory at his own expense in the basement
of his home.
 Buchheim is remembered for his pioneer work in
experimental pharmacology.
 He introduced the bioassay to pharmacology.
 His reputation is overshadowed by that of his student, Oswald
Oswald Schmiedeberg (1838–1921)
 Generally recognized as the founder of modern pharmacology.
 Schmiedeberg obtained his medical doctorate in 1866 with a thesis
on the measurement of chloroform in blood.
 In 1872, he became professor of Pharmacology at the University of
Strassburg.
 In 1878, he published a classic text, Outline of Pharmacology.
 In 1885, he introduced urethane as hypnotic.
 In his 46 years at Strasburg, Schmiedeberg trained most of the
men who became Professors at other German universities & in
several foreign countries.
 He was largely responsible for the preeminence of the German
Pharmaceutical Industry up to World War II.
 In the United States, the first chair in Pharmacology was
established at the University of Michigan in 1890 under John
John Jacob Abel (1857—1938)
 An American Pharmacologist, PhD from the University
of Michigan and trained under Schmiedeberg.
 In the United States, the first chair in pharmacology
was established at the University of Michigan in 1890
under John Jacob Abel.
 In 1893, Abel went to Johns Hopkins University in
Baltimore, where he had a long and brilliant career.
 Also k/a FATHER OF AMERICAN PHARMACOLOGY.
John Jacob Abel’s Contributions
 Gave the name Pharmacology as a subject (earlier k/a Materia
Medica).
 He was second to isolate epinephrine (1897–1898) from
adrenal gland extracts (first was Napoleon Cybulski in 1895).
 Isolated amino acids from the blood (1914)
 Isolation of histamine from pituitary extract (1919)
 Preparation of pure crystalline insulin (1926).
 His student Reid Hunt discovered acetylcholine in adrenal
extracts in 1906.
Friedrich Serturner
 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 alkaloid was named
morphine, for Morpheus, the Greek god of sleep.
 Although humans are no longer used as laboratory
animals, they are essential in clinical pharmacology.
OTTO LOEWI (1873—1961)
 A German Pharmacologist, brilliantly obtained his
doctor’s degree with a thesis about “techniques of
isolations of frog’s heart.
 1902 In London, in Starling’s laboratory, he met for the
first time Henri Hallet Dale, who was to become a
lifelong friend.
 1909 He was appointed to the Chair of Pharmacology in
Graz.
 1921 He proved, the chemical transmission of the
nerve impulses & in 1936. He received the Nobel price,
with Henri Dale.
OTTO LOEWI CONTRIBUTIONS
 He designed his most famous experiment, which provided the
first evidence for the existence of chemical transmission in a
synapse.
 The legend tells that he had the idea of the experiment in a
dream and that he ran to the lab in the middle of the night.
 The experiment was very simple and became a prototype for all
investigations of chemical factors in the nervous system.
 OTTO LOEWI: He cut out two hearts from frogs and perfused
them with a warm physiological solution (Ringer). He then
stimulated the vagus nerve to one of the hearts. As a
consequence, there was a strong inhibition in this heart beats (R).
The second heart was unaffected. However, when he perfused
the second heart with the outflow of the perfusion of the first one,
he achieved exactly the same effect (D). It was therefore
concluded that some substance produced at the parasympathetic
SIR HENRY HALLET DALE
 An English Pharmacologist. Received his M.D. from Cambridge in
1909. Worked under John Langle & Paul Ehrlich , also a Fast friend
of Otto Loewi.
 Dale became the Director of the Dept.
of Biochemistry and Pharmacology at the National Institute for Medical
Research in London in 1914.
 Also served as President of the Royal Society from 1940 to 1945.
SIR HENRY HALLET DALE CONTRIBUTIONS IN
PHARMACOLOGY
 Distinguished Muscarinic & Nicotinic receptors in 1914.
 First identified acetylcholine in 1914 as a possible neurotransmitter, Loewi showed its
importance in the nervous system. (shared the 1936 Nobel Prize for Physiology or
Medicine.)
 Dale's principle ( Dale's Law). This principle states that each neuron releases only one type of
neurotransmitter.
Colonel Ram Nath Chopra (1882—1973)
 k/a FATHER OF INDIAN PHARMACOLOGY
 Obtained MD degree from Cambridge University in 1908
 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 the
Calcutta medical college
 From 1941 to 1957: he was Director of the Drug Research Lab at
Srinagar
Colonel Ram Nath Chopra: CONTRIBUTIONS :
 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.
Paul Ehrlich (1854--1915)
 German scientist in the fields of hematology, immunology, and
chemotherapy.
 He is noted for curing syphilis and for his research in autoimmunity.
 He coined the term chemotherapy and popularized the concept of a
magic bullet.
 Also coined the term Receptor (earlier called as receptive substance
by Langley).
 Ehrlich skillfully transformed diphtheria antitoxin along with Emil Adolf
von Behring, into an effective preparation, his first world renown
achievement. However, von Behring cheated Ehrlich out of both
recognition and financial reward. Only von Behring received the first
Nobel Prize in Medicine, in 1901.
 In 1906 he discovered the structural formula of atoxyl, a chemical
compound which had been shown to be able to treat sleeping
sickness.

Paul Ehrlich (1854--1915)
 In 1909 he and his student Sahachiro
Hata developed Salvarsan, a treatment effective
against syphilis. Salvarsan became the most widely prescribed
drug in the world, most effective drug for treating syphilis
until penicillin became available in the 1940s.
 Known as FATHER OF CHEMOTHERAPY.
Alexander Fleming (1881-1955)
 Scottish biologist and pharmacologist.
 His best-known discoveries are the discovery of the:
₋ enzyme lysozyme in 1923
₋ antibiotic penicillin from the mold Penicillium notatum in
1928 which was a discovery by chance. On 3 September
1928, Fleming returned to his lab. after vacation. Before
leaving, he had stacked all his cultures of staphylococci on
a bench in a corner of his laboratory.
₋ On returning, Fleming noticed that one culture was
contaminated with a fungus, and that the colonies of
staphylococci that had immediately surrounded it had
been destroyed, whereas other colonies farther away were
normal.
 He shared the Nobel Prize in Physiology or Medicine in 1945
with Howard Florey and Ernst Chain who purified penicillin.
Sir Frederick Banting & Charles Best
 Sir Frederick Grant Banting, (1891 –1941) was
a Canadian medical scientist & doctor.
 Charles Best February (1899 – 1978) was his assistant.
 Known for the discovery of insulin—one of the most significant
advances in medicine, enabling an effective treatment
for diabetes.
 In 1921, Banting traveled to Toronto to visit J.J.R. Macleod at
University of Toronto, where he used his lab for this discovery.
Banting & Best
 He also supplied Banting with ten dogs to experiment on, and
two medical students, Best and Clark Noble, to use as lab
assistants.
 Since Banting only required one lab assistant, Best and Noble
flipped a coin & Best won the coin toss, and took the first shift as
Banting's assistant.
 Loss of the coin toss was very unfortunate for Noble as Best
worked with Banting for the entire summer (and eventually
shared half his Nobel Prize money and a large part of the credit
for the discovery of insulin with the winner of the toss).
 In 1923, Banting and J.J.R. Macleod won the Nobel Prize in
Medicine for the discovery of insulin, & Nobel prize committee
ignored Best. This incensed Banting, who voluntarily shared half
of his award money with Best.
Gerhard Domagk (1895-1964)
 German pathologist and bacteriologist.
 Done extensive work on infections & antibiotics.
 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.
 In 1939, Domagk received the Nobel Prize in Physiology or
Medicine for this discovery, the first drug effective
against bacterial infections.
Daniel Bovet (1907—1992)
 Swiss born Italian pharmacologist.
 In the early 1930’s Bovet and his coworkers conducted a series of
experiments on Prontosil & they concluded that Prontosil derived its
therapeutic powers due to the presence of sulphanilamide.
 In 1937 Bovet and his research student Anne Marie Staub succeeded
in synthesizing the first antihistaminic Thymoxidiethylamine.
 Thymoxidiethylamine was too toxic to be used so he continued with
hundreds of experiments to find a more human body friendly
antihistamine.
 After years of research he succeeded in discovering Pyrilamine
(mepyramine) a very important histamine.
 In 1947 he discovered gallamine when he was looking for a synthetic
substitute for curare
 Isolated succinylcholine, a muscle relaxant now used in conjunction
with anesthesia during certain surgical procedures.
 In 1957 he was awarded the Nobel Prize in Physiology or Medicine for
his discoveries.
Louis Lasagna (1923—2003): Father of Clinical Pharmacology.
 Famous American Clinical Pharmacologist.
 Medical degree from Columbia University in 1947.
 Lasagna joined the faculty of Johns Hopkins University in 1954,
where he established the first ever clinical
pharmacology department.
 In 1964, Lasagna revised the Hippocratic Oath
 Conceptualized controlled clinical trials and the placebo effect.
 Lasagna's work led to the improvement of controlled clinical
trials to test drug effectiveness, and improved the regulation of
drugs for effectiveness and safety.
 Lasagna's Law: The incidence of patient availability sharply
decreases when a clinical trial begins and returns to its original
level as soon as the trial is completed.
Sir James Black (1924-2010)
 A Scottish Pharmacologist
 Studied Medicine at Univ. of St. Andrew.
 In 1950, he joined the University of Glasgow.
 He was interested in the effect of adrenaline on the human
heart.
 Joined ICI Pharmaceuticals in 1958.
 1n 1964 he joined Smith, Kline and French for whom he worked
for nine years until 1973.
 He was awarded the Nobel Prize for Medicine in 1988 for his
work.
Sir James Black (1924-2010)
Sir James Black’s Major Contributions:
 He established the Physiology Department at Univ of Glasgow.
 He developed Propranolol while working for ICI, which later
became the world's best-selling drug.
 Black was developing a similar method of treatment for stomach
ulcers, but ICI did not wish to pursue the idea so Black resigned
in 1964 and joined Smith, Kline and French. While there, Black
developed his second major drug, cimetidine (brand name
Tagamet ) in 1975 and soon outsold propranolol to become the
world's 1st billion dollar drug.
Louis J. Ignarro, Robert Furchgott and Ferid Murad
 Louis J. Ignarro (born May 31, 1941) is an Italian
American pharmacologist.
 Robert Francis Furchgott (1916 – 2009) was an
American biochemist.
 Ferid Murad (born September 14, 1936) is an Albanian-
American physician and pharmacologist.
 Their main contribution is the discoveries concerning nitric
oxide as a signaling molecule in the cardiovascular system.
 Co-winners of the 1998 Nobel Prize in Physiology or Medicine.
Other Scientists & Their Contributions
 Thomas Renton Elliott: Elaboration of the Concept of Chemical
Neurotransmission
 John Langley (1878): Receptor concept (called it Receptive
substance
 William Henry Howell & Jay McLean (1916): Discovered Heparin
from Canine Liver
 Raymond Ahlquist (1948): Existence of two types of adrenergic
receptors i.e. Alpha & Beta Receptors
 G.Brotzu (1948): discovered Cephalosporins
 Selman Waksman: discovered streptomycin, the first antibiotic
effective against tuberculosis - Nobel Prize (1952)
 Ulf von Euler, Julius Axelrod, and Sir Bernard Katz: the processes
involved with the biosynthesis, release, actions, and inactivation
of neurotransmitters (Nobel Prize 1970)
Other Scientists & Their Contributions
 Earl Wilbur Sutherland Jr.: He discovered cAMP as 2nd messenger
concerning the mechanisms of the action of hormones,"
especially epinephrine ( Nobel Prize in in 1971)
 Sir John Robert Vane: worked on aspirin & discovered that it
inhibits prostaglandin biosynthesis ( Nobel Prize 1982)
 Martin Rodbell & Alfred G. Gilman: Known for their discovery of
G-proteins and the role of these proteins in signal transduction in
cells (Nobel Prize 1994)
Some Scientists in History of Anesthetics
 Nitrous oxide: Synthesized by Priestley in 1774, 1st clinically
used by Humphery Davy who used it on himself for toothache
and called it as Laughing gas.
 Horace Wells: Used N2O for tooth extraction & patient cried in
pain. He became very frustrated and chloroform addict and
committed suicide by cutting his femoral artery.
 Ether: Prepared by Valeus Cordusand was k/a ‘sweet oil of
vitroil’. First public demonstration was given by W.T.G Morton on
16th October 1846 (World Anesthesia Day).
 Chloroform: First use was done by Simpson but John Snow
popularized it by using it successfully in 4,000 patients (also used
on Queen Victoria for birth of her 8th child).
 Cocaine was 1st used by Carl koller for anesthetizing cornea.
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
Louis Lasagna: Father of Clinical Pharmacology
Zebron Thole: Future Father of Zambian Pharmacology
Nobel Laureates In Pharmacology
1908, Elie Metchnikoff, Paul Ehrlich: First antimicrobial drugs
(“magic bullet”).
1923, Frederick Banting, John Macleod: Isolation and discovery of
insulin and its application in the treatment of diabetes.
1936, Sir Henry Dale, Otto Loewi: Chemical transmission of nerve
impulses.
1945, Ernst Chain, Sir Alexander Fleming, Sir Howard Florey:
Discovery of penicillin and its curative effect in various infectious
diseases.
1950, Edward Kendall, Tadeus Reichstein, Philip S. Hench:
Hormones of the adrenal cortex, their structure and biological
effects.
1957, Daniel Bovet: Antagonists that block biologically active
amines, including the first antihistaminic.
Nobel Laureates In Pharmacology
1971, Earl Sutherland Jr.: Mechanisms of the action of hormones
with regard to inhibition and stimulation of cyclic AMP.
1982, SuneBergström, Bengt Samuelsson, John R. Vane: Discovery
of prostaglandins and the mechanism of action of aspirin which
inhibits prostaglandin synthesis.
1988, Sir James W. Black, Gertrude B. Elion, George H. Hitchings:
Development of the first beta-blocker, propranolol, and anticancer
agents that block nucleic acid synthesis.
1994, Alfred Gilman, Martin Rodbell: Discovery of G proteins and
the role of these proteins in signal transduction in cells.
1998, Robert Furchgott, Louis Ignarro, Ferid Murad: Role of NO as a
signaling molecule in the cardiovascular system.
2000, Arvid Carlsson, Paul Greengard, Eric Kandel: Role of
dopamine in schizophrenia and signal transduction in the nervous
system leading to long-term potentiation.
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 libido-enhancing effect of LEVODOPA
Serendipity in Pharmacology
 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 first antidepressants, imipramine and iproniazid were 1st
used in schizophrenics (imipramine) & in the t/t of TB (iproniazid).
 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
Serendipity in Pharmacology
 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 nitrous
oxide considerably dulled the sensation of pain, even if the
inhaler was still semi-conscious.
REFERENCES
1. Goodman and Gilman’s: The Pharmacological Basis of Therapeutics. 12th edition
2. Clinical Pharmacology: Bennett and Brown 10th edition
3. Basic and clinical pharmacology: Katzung, Masters and Trevor: 11th edition
4. A Brief History of Great Discoveries in Pharmacology. Rubin PR. Pharmacol Rev 2007; 59:
289–359.
5. "All Nobel Prizes in Physiology or Medicine". Nobelprize.org.
6. "I have been trying to point out that in our lives chance may have an astonishing influence
and, if I may offer advice to the young laboratory worker, it would be this - never to neglect
an extraordinary appearance or happening.” Alexander Fleming. Thank you!
7. Some Pharmacologists in History. William Withering, 1741-1799 (digitalis).
8. Claude Bernard 1813-1878 (d-tubo curare).
9. Friedrich Sertürner 1783--1841 (morphine).
REFERENCES
10. Rudolf Buchheim 1820-1879 (1st Pharmacology Laboratory, University of Dorpat (now
Tartu, Estonia).
11. Oswald Schmiedeberg 1838-1921 (Strassburg, now Strasbourg, trained many
pharmacologists).
12. John Langley 1852--1926 (Receptor concept).
13. Paul Ehrlich 1854-1915 (Receptor concept).
14. Otto Loewi, Henry Dale (Neurotransmission).