How was your drug discovered?
The drug Phenobarbital has a long history; in fact the
discovery began in 1865, over a century ago. In 1890 at the German Chemical Society meeting
a German chemist names August Kekule reported that he had been working with chemical
structures and he had noticed that many of the structures he worked with had
one thing in common, they had ring like shapes.
He had researched these new structures for about 20 years and had
finally decided to speak up.
Despite the fact that Kekule set a great foundation for the
discovery of Phenobarbital he was no the one who discovered it. Twenty-two years after the Chemical Society
meeting a man named Alfred Hauptmann was a clinical assistant in Freiburg who
was annoyed at the fact that he was awakened at night by patients who had
seizures. So he gave them Phenobarbital as a hypnosis medication and noticed
something amazing… the seizures were being suppressed by the drug.
Astonished by this new observations; Hauptmann decided to
pick patients who had a long history of seizures. The test subjects were
administered different doses of Phenobarbital at different times of the day.
The Phenobarbital was administered as medication tablets for example some of
the tablets were 300 mg or 200 mg tablets.
He noticed that the difference in the amount of drugs given to the
patient was the determining factor of how effective the drug was.
In conclusion Hauptmann said that he recommended using
Phenobarbital in “genuine” epilepsy treatment. This is the earliest record of
the discovery of Phenobarbital but shortly after Hauptmann published his work
many other scientists around the world did the same or a similar experiment. Like
in Britain were the scientist Golla who also had the same success in proving
that Phenobarbital worked. This new drug discovery jumped from nation to nation
and pretty soon it was one of the drug of first choice when dealing with
epilepsy treatment.
In this picture we have August Kekule the chemist and the
ring structure he worked with:
In this picture we have Alfred Hauptmann the man who
discovered phenobarbital:
How is this drug manufactured?
To make the drug Phenobarbital there are eight possible ways
or reactions that are able to give us the desired drug. But the most used method or procedure to
create Phenobarbital is the following. We need to react ethyl oxalate ester and
pheylacetonitrile once they have reacted we need to add iodoethane into the
mix, this will give us “Product D”. Then we get “product D” and heat it up so It
turns into a decarboxylation reaction and yields “Product E”. from there
product E condenses with Urea and the product crystalizes and Product F is yield
also known as Phenobarbital.
In this picture we see a visual of how the drug is created:
-Alejandro Guzman
For more information Visit:
http://onlinelibrary.wiley.com/store/10.1111/epi.12026/asset/epi12026.pdf?v=1&t=i7sin5t9&s=7ca53cb15a1ea102d42ad603371d1bcb2b01d421
http://pubchem.ncbi.nlm.nih.gov/compound/phenobarbital#section=Top
