A class of drug that has been trialled in osteoarthritis has been implicated in the clinical trial last week that went tragically wrong, leaving one volunteer dead and four with neurological symptoms of varying severity.

The Portuguese pharmaceutical company that sponsored the trial, Bial, has confirmed that the drug involved in the phase I study was a Fatty acid amide hydrolase (FAAH) inhibitor known as BIA 10-2474.

FAAH inhibitors are enzymes that break down endogenous compounds that act as neurotransmitters via the cannabinoid receptors.

According to Professor Sir Munir Pirmohamed, a pharmacologist and Vice President of the British Pharmacological Society, the idea behind the development of FAAH inhibitors is to preserve the analgesic effects without having the negative effects of cannabinoids.

There are two FAAH enzymes, FAAH1 and FAAH2, but the majority of drugs developed inhibit FAAH1 and can also have effects on FAAH2.

Some FAAH1 inhibitors have already been tested in humans, without the adverse effects seen with BIA 10-2474, explained Professor Pirmohamed.

For instance one trial tested the FAAH PF-0445784 in 74 patients with osteoarthritis and although was not effective, was well tolerated and did not have the cannabinoid-type adverse events (Pain. 2012 Sep;153(9):1837-46).

“FAAH inhibitors can be reversible or irreversible.  There are reports that BIA 10-2474 was an irreversible inhibitor, but I have not been able to find any scientific publications by searching the literature databases” said professor Pirmohamed in a statement issued by the Australian Science Media centre.

“ It is interesting to note that reviews of FAAH inhibitors mention many drugs in development by many companies, but BIA 10-2474 is hardly mentioned.”

“The lack of information on BIA 10-2474 in the peer reviewed scientific literature from the manufacturer is surprising” he said.