The Search for a Safer Painkiller
In the early 1950s, the landscape of pain management was dominated by aspirin, a salicylic acid-based nonsteroidal anti-inflammatory drug (NSAID) that had been in use since the late 19th century. While effective, aspirin had significant drawbacks, particularly severe gastrointestinal side effects when administered for treating chronic conditions like rheumatoid arthritis. The Boots Pure Drug Company in Nottingham, England, sought a new, safer remedy for arthritis, commissioning a research team to find a drug that could offer similar anti-inflammatory properties without the toxic long-term effects.
The Boots Pure Drug Company team
At the heart of this research initiative was Dr. Stewart Adams, a pharmacologist who began his work at Boots in 1952. Adams was joined in 1956 by chemist John Nicholson, and together, they spearheaded the development process. Their collaboration was crucial, combining Adams' pharmacological insights with Nicholson's chemical expertise. Their initial strategy involved exploring hundreds of compounds derived from salicylates, but none proved superior to aspirin. The team persisted, shifting their focus to investigating propionic compounds, which eventually led them to the breakthrough compound.
The Road to Ibuprofen
The research journey was marked by years of exhaustive testing and numerous setbacks, as several promising compounds failed clinical trials due to side effects. After a decade of work, the team finally focused on a compound known as 2-(4-isobutylphenyl) propionic acid. This compound was developed and synthesized, leading to a patent application filed in 1961. The name "ibuprofen" was later coined based on the chemical name's functional groups: ibutyl, propionic acid, and fenyl.
A famous self-test
Before ibuprofen was released to the market, Dr. Adams became the drug's first human test subject in a rather unconventional manner. While preparing to give a speech in Moscow, he found himself suffering from a debilitating hangover. Taking a dose of his newly developed compound, he was amazed to find that his headache had completely subsided, allowing him to deliver his speech without issue. This personal anecdote, which demonstrated the drug's powerful analgesic properties, has become a famous part of ibuprofen's history.
From Prescription to Over-the-Counter
Following successful clinical trials, ibuprofen was first launched as a prescription drug in the United Kingdom in 1969 under the brand name Brufen. The United States followed in 1974, with the Upjohn Company marketing it as the prescription-only arthritis medication, Motrin. It wasn't until the 1980s that regulatory bodies in the UK and US approved ibuprofen for over-the-counter (OTC) sales at lower dosages. In the UK, it was branded as Nurofen in 1983, and in the US, Advil and Nuprin were introduced in 1984. The Boots worldwide patent for ibuprofen expired in 1985, paving the way for numerous generic versions to enter the market.
The mechanism of action
Ibuprofen works by inhibiting the cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. These enzymes are responsible for producing prostaglandins, hormone-like substances that play a major role in causing inflammation, pain, and fever. By blocking these enzymes, ibuprofen reduces prostaglandin production, thereby alleviating symptoms. While effective, the inhibition of COX-1 is also responsible for some of the common gastrointestinal side effects associated with NSAIDs.
How Ibuprofen Compares to Other Pain Relievers
| Feature | Ibuprofen | Aspirin | Naproxen | Acetaminophen |
|---|---|---|---|---|
| Drug Class | NSAID | NSAID | NSAID | Analgesic & Antipyretic |
| Mechanism | Inhibits COX-1 and COX-2 | Irreversibly inhibits COX-1 and COX-2 | Inhibits COX-1 and COX-2 | Inhibits CNS prostaglandin synthesis |
| Time to Onset | ~30-60 minutes | ~20-30 minutes | ~1 hour | ~30-60 minutes |
| Duration of Action | ~4-6 hours | ~4-6 hours | Up to 12 hours | ~4-6 hours |
| Primary Uses | Pain, fever, inflammation | Pain, fever, inflammation, anti-platelet | Pain, fever, inflammation | Pain, fever |
| Major Side Effects | GI bleeding, kidney issues | GI bleeding, Reye's syndrome in children | GI bleeding, cardiovascular risk | Liver damage |
Key milestones in ibuprofen's history
- 1953: Dr. Stewart Adams begins research for a new arthritis treatment at Boots Pure Drug Company.
- 1956: Chemist John Nicholson joins Adams, forming the core research team.
- 1961: The patent for 2-(4-isobutylphenyl) propionic acid, or ibuprofen, is filed.
- 1969: Ibuprofen is first released as a prescription drug (Brufen) for rheumatoid arthritis in the UK.
- 1974: Ibuprofen (Motrin) is introduced by prescription in the United States.
- 1983-1984: Ibuprofen becomes available for over-the-counter sale in the UK (Nurofen) and US (Advil).
- 1985: Boots' worldwide patent for ibuprofen expires, allowing for generic production.
Conclusion
The story of who invented ibuprofen is a testament to persistent scientific research and collaboration. The journey from a company initiative to find a safer alternative to aspirin, through years of experimentation, a memorable accidental self-test, and finally to regulatory approval, highlights the rigorous process of drug development. The work of Stewart Adams and John Nicholson fundamentally changed pain management, making a safe and effective treatment for pain, inflammation, and fever accessible to millions worldwide. Today, ibuprofen's legacy is evident in its status as a staple in medicine cabinets across the globe and its place on the World Health Organization's List of Essential Medicines.
For more information on the discovery of ibuprofen, you can read about the inventors at the National Inventors Hall of Fame.
