Drug History Part 2

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