Serendipity
in
Pharmacology
Presenter: [Link] Maret
Moderator :Dr.C.S Bharathan
28/06/2014
Definition
The occurrence and development of
events by chance in a happy or
beneficial way.
OR
‘A Pleasant Surprise’
Origin
Serendip is the old Arabic name for Ceylon,
now Sri Lanka.
Refers to the ‘Three Princes of Serendip’
Term coined by Horace Walpole , an English
man on June 28 1754 in a letter Horace Mann
Serendipity in Pharmacology
Antibiotics
Psycho-Therapeutic Drugs
Cardiovascular Drugs
Anticancer Drugs
Others
Antibiotics
Penicillin by Alexander Fleming in 1928.
He failed to disinfect cultures of bacteria when
leaving for his vacations, only to find them
contaminated with Penicillium molds, which
killed the staphylococcal colonies.
He named the antibacterial substance
“Penicillin,” after Penicillium notatum,
Howard Florey in 1941and his team developed a
methodology for the extraction and production of
penicillin.
To obtain sufficient quantity of the substance for
clinical use, the original strain, Penicillium
notatum, had to be replaced by Penicillium
chrysogenum.
Sulfonamides
Gerhard Domagk used an Azo dye(Prontosil Rubrum)
used to dye leather for teatment of streptococcal
infection in mice and was successful
Tried in a child with staphylococcal infection with
success
Prontosil contained a sulfonamide group
Psycho-Therapeutic Drugs
Chlorpromazine
The first anti-psychotic drug, chlorpromazine, was
discovered by French pharmacologist Henri Laborit.
He wanted to add an anti-histaminic to
prevent surgical shock but noticed that patients
treated with it were unusually calm before the
operation.
Discovery Imipramine
Psychiatrist Roland Kuhn, staff medical director in the
Cantonal psychiatric clinic received a substance with
the same side chain as chlorpromazine synthesized by
Franz Häfliger and Walter Schindler
BUT it lacked neuroleptic activity.
Some patients even showed a deterioration in their
schizophrenic picture, passing to a state agitation.
Patients diagnosed of depressive psychosis
experienced a significant improvement in
their general state in only a few weeks.
The anti depressive effect of this substance
was identified, later called Imipramine
Chloral Hydrate
Otto Liebreich assumed that one of the components
into which chloral hydrate splits in the body is
chloroform
Although no chloroform resulted from the
degradation of chloral hydrate, chloral hydrate became
the first synthetically produced reliable hypnotic
Valproic Acid
Valproic acid, was a substance synthesized in 1881 by
the American chemists Beverly S. Burton as organic
solvent
George Carraz, tried to evaluate the experimental
anticonvulsant activity of a series of compounds of
khelline3 and used valproic acid as a solvent agent.
Using the pentylenetetrazole model ,discovered that
all the solutions that contained valproic acid,
regardless of the khelline, had anticonvulsant activity
Lithium
In 1940 John cade was studying the effect of Urea in
mood disorders
He used Lithium Urate and paradoxically observed a
calming effect
LSD
The psychedelic effects of LSD by Albert
Hofmann
He had the first acid trip in history, while
cycling to his home in Switzerland
This is commemorated among LSD users
annually as Bicycle Day.
Chlordiazepoxide
Synthesised by accident in 1961 as a result of a
reaction that went wrong in the laboratories of
Hoffman-La Roche.
Leo sterbach Synthesized several heptoxdiazine
compounds in an effort to develop synthetic dyes
but by mistake synthesised benzoxadiazepenes
Its unexpected pharmacological activity was
recognised in a routine screening procedure
Cardiovascular Drugs
Heparin
Discovered by John Mclean in 1916 who was working
to dicover the clotting factors in blood
Found out liver contained a powerful anticoagulant ,
named Heparin by William Howell.
Streptokinase
William tillet a bacteriologist studying on streptococci
and body’s defence mechanism in clumping it found
out the clotted blood was liqufied
In 1933 he reported that streptococci produced a
protein that inactivates a critical factor in clot
formation
Aspirin
Obtained from bark of willow tree was used as a
painkiller for many years
In 1940 an ENT surgeon Lawrence Craven gave
Aspergum chewing Gum to Post-Tonsillectomy
patients noticed increased gum bleed
He used it in his patients to prevent heart attacks
and stroke and was successful
Warfarin
The oral anticoagulants emerged from veterinary
research in the 1920s on a hemorrhagic disorder afflicting
cattle that consumed spoiled sweet clover hay.
Karl Link and his University of Wisconsin team to the
identification of dicumarol as the offending agent in 1939.
Link later developed warfarin as a rodenticide, but its use
in humans soon followed in the 1950s.
Sildenafil
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.
Anticancer Drugs
Methotrexate
In 1933 Lucy wills a physician found Marmite
improved Anemia in Textile workers , the content of
which was found to be Folic Acid
Researchers used liver extract to mice with tumours
and found good result
But when Sidney Farber uesd folic acid in peadiatric
leukemia patients the results where devastating
Anticancer Drugs contd…
Farber then tried Antagonist of folic acid and was
succesful
In 1948 he discovered Aminopterin a folic acid
antagonist
In 1949 methotrexate was dicovered and found to be
safer
Anticancer Drugs contd…
Platinum compounds
Barnet Rosenberg was studying the effect of electric
current in sterilizing medical utensils and preserving
food by passing current through platinum wire
He found that the process arrested the growth of
[Link] in the nutrient broth
It was later found to be due to th effect of Platinum
ionds and not due to the current
Mustine – a derivative of mustard gas .
In 1943, physicians noted that the white cell counts of
US soldiers, accidentally exposed mustard gas
shells were decreased
Mustard gas was investigated as a therapy
for Hodgkin's lymphoma.
Others
Sulfonylureas
Marcel Janbon, an infectious disease physician
experimenting with a new sulfonamide to treat the
numerous cases of typhoid fever in wartime .
Janbon reported post treatment convulsions,
prolonged coma, and severe falls in blood glucose in
some of his patients to Loubatières, who had been
conducting diabetes research in dogs .
In 1946, after several more years’ work,
Loubatières concluded that sulfonamide was an
insulin secretagogue acting directly on the
pancreas
A decade later in Germany the first sulfonylureas
were developed for use in diabetes.
Pethidine
Synthesized in 1939 as a potential anticholinergic
agent by the German chemist Otto Eislib, its analgesic
properties were first recognized by Otto Schaumann .
N2O
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
Minoxidil
Originally it was an oral agent for treating Hypertension
It was observed that bald patients treated with it
grew hair too.
OTTO LOEWI
1921 He proved, the chemical transmission of
the nerve impulses& in 1936 He received the
Nobel price, with Henri Dale.
1873 - 1961
32
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.
33
Others
Amphetamine
Clonidine Phenylbutazone
Cromoglycate Phenolphthalein
Cyclosporin Praziquantel
Diethylstilbestrol Prednisone
Diphenoxylate Propafenone
Disulfiram Tamoxifen
Ether Griseofulvin
Etomidate Mifepristone
Thank You
“Chance favors
the prepared
mind”
Louis Pasteur
