71
sugar in the dog’s urine and that the dog was suffering from something indistinguishable
from diabetes mellitus. Thus, for the first time, experimental diabetes was produced and
the earliest glimpse was given into the possible cause of that disease.4 The more common
story was that Minkowski’s attention to the urine was due to flies attracted to the sugar.
Minkowski, however, denied this version.5 His denial is not surprising, as it is unsettling
for scientists to admit that their discoveries have occurred purely by accident.
Psychotropic Drugs
Major classes of psychotropic drugs including lithium, chlorpromazine, imipramine,
reserpine and chlordiazepoxide were serendipitously discovered in the 1950s and 1960s.
Lithium was discovered in research on urine samples from manic patients. Urea was
found to be more abundant in their urine than in normal patients and more toxic when
injected into guinea pigs. The researcher postulated that the toxicity might be due to
the presence of uric acid. He carried out a number of tests to determine the urea’s toxic-
ity using varying concentrations of uric acid. Because uric acid is highly insoluble, its
most soluble salt—lithium urate—was used in his experiments. The salt was found to
produce a calming action on guinea pigs, an effect not due to the urate component but
to the presence of lithium ions.6 Chlorpromazine was originally designed to be used
for its antihistamine effects and was found to be effective in treating schizophrenia.
Imipramine, a chemically similar drug, was found to be surprisingly inactive against
schizophrenia, but effective for its antidepressant effects. Reserpine had been designed to
treat high blood pressure when it was found to be useful in treating psychiatric patients.7
Chlordiazepoxide was surprisingly effective as a tranquillizing drug, even though similar
compounds had no such properties. During its synthesis, chlordiazepoxide underwent an
unexpected intra-molecular arrangement.8
Existing Drugs With New Uses
Many other drugs have been accidentally found to benefit a new indication.9 The list
includes dimenhydrinate, mechlorethamine, aspirin, lidocaine, minoxidil, iproniazid,
sildenafil, thalidomide, bupropion and eflornithine. Dimenhydrinate, an antihistamine,
became one of the drugs of choice for motion sickness.10 Mechlorethamine was used as a
poisonous gas during World War I. Because of its destructive effect on white blood cells
it was found useful in treating Hodgkin’s disease and other lymphomas. Mustargen (the
trade name) was the first cancer chemotherapy agent approved by the US Food and Drug
Administration. Aspirin, used for more than 100 years for pain and fever, is now recom-
mended for preventing heart attacks. Lidocaine, a local anesthetic, is now used to treat
cardiac arrhythmias. Minoxidil, used topically to grow hair, was originally, and is still
used for hypertension.11 Iproniazid, an early antidepressant, was initially employed to
cure tuberculosis. The drug’s antidepressant effects were discovered in a chronic tubercu-
losis ward where patients who took the drug become euphoric.12 Sildenafil (Viagra) was a
compound developed to treat angina. Thalidomide, a teratogen, was originally designed
as a sedative now it is a mainstay for patients with multiple myeloma and used to treat
certain forms of leprosy.13 Bupropion, an antidepressant, was inadvertently found to lessen
the effects of nicotine. Eflornithine (Vaniqa) was useful in treating African sleeping sick-
ness. It was later discovered to suppress the enzyme that causes facial hair to grow.14
Future Implications for Drug Discovery
Research today is targeted toward a specific goal and new drug discoveries are the result
of intense planning, interminable research, long-term clinical studies, laborious and com-
prehensive data collection and statistical analysis. There is almost no room for significant
variation. In light of the expenses involved and tight schedules, scientists have little time
Serendipity and Drug Discoveries
sugar in the dog’s urine and that the dog was suffering from something indistinguishable
from diabetes mellitus. Thus, for the first time, experimental diabetes was produced and
the earliest glimpse was given into the possible cause of that disease.4 The more common
story was that Minkowski’s attention to the urine was due to flies attracted to the sugar.
Minkowski, however, denied this version.5 His denial is not surprising, as it is unsettling
for scientists to admit that their discoveries have occurred purely by accident.
Psychotropic Drugs
Major classes of psychotropic drugs including lithium, chlorpromazine, imipramine,
reserpine and chlordiazepoxide were serendipitously discovered in the 1950s and 1960s.
Lithium was discovered in research on urine samples from manic patients. Urea was
found to be more abundant in their urine than in normal patients and more toxic when
injected into guinea pigs. The researcher postulated that the toxicity might be due to
the presence of uric acid. He carried out a number of tests to determine the urea’s toxic-
ity using varying concentrations of uric acid. Because uric acid is highly insoluble, its
most soluble salt—lithium urate—was used in his experiments. The salt was found to
produce a calming action on guinea pigs, an effect not due to the urate component but
to the presence of lithium ions.6 Chlorpromazine was originally designed to be used
for its antihistamine effects and was found to be effective in treating schizophrenia.
Imipramine, a chemically similar drug, was found to be surprisingly inactive against
schizophrenia, but effective for its antidepressant effects. Reserpine had been designed to
treat high blood pressure when it was found to be useful in treating psychiatric patients.7
Chlordiazepoxide was surprisingly effective as a tranquillizing drug, even though similar
compounds had no such properties. During its synthesis, chlordiazepoxide underwent an
unexpected intra-molecular arrangement.8
Existing Drugs With New Uses
Many other drugs have been accidentally found to benefit a new indication.9 The list
includes dimenhydrinate, mechlorethamine, aspirin, lidocaine, minoxidil, iproniazid,
sildenafil, thalidomide, bupropion and eflornithine. Dimenhydrinate, an antihistamine,
became one of the drugs of choice for motion sickness.10 Mechlorethamine was used as a
poisonous gas during World War I. Because of its destructive effect on white blood cells
it was found useful in treating Hodgkin’s disease and other lymphomas. Mustargen (the
trade name) was the first cancer chemotherapy agent approved by the US Food and Drug
Administration. Aspirin, used for more than 100 years for pain and fever, is now recom-
mended for preventing heart attacks. Lidocaine, a local anesthetic, is now used to treat
cardiac arrhythmias. Minoxidil, used topically to grow hair, was originally, and is still
used for hypertension.11 Iproniazid, an early antidepressant, was initially employed to
cure tuberculosis. The drug’s antidepressant effects were discovered in a chronic tubercu-
losis ward where patients who took the drug become euphoric.12 Sildenafil (Viagra) was a
compound developed to treat angina. Thalidomide, a teratogen, was originally designed
as a sedative now it is a mainstay for patients with multiple myeloma and used to treat
certain forms of leprosy.13 Bupropion, an antidepressant, was inadvertently found to lessen
the effects of nicotine. Eflornithine (Vaniqa) was useful in treating African sleeping sick-
ness. It was later discovered to suppress the enzyme that causes facial hair to grow.14
Future Implications for Drug Discovery
Research today is targeted toward a specific goal and new drug discoveries are the result
of intense planning, interminable research, long-term clinical studies, laborious and com-
prehensive data collection and statistical analysis. There is almost no room for significant
variation. In light of the expenses involved and tight schedules, scientists have little time
Serendipity and Drug Discoveries