Concerns over the potential dangers of an experimental drug have arisen after a patient died from the prescription drug amtran – a company producing the drug has stopped manufacturing it, and the FDA warned clinicians to hold off on prescribing amtran until safety issues could be investigated.
Amtran is used to treat transient flushing episodes that can occur after chemotherapy. The drug, first authorised in the US in 2012, is the first in a series of neuroprotective molecules from Arena Pharmaceuticals, which act on the brain to reduce flushing of the eye, lower blood pressure and improve vision.
Amtran is meant to work by breaking down a substance called aminomethylhydrofolate reductase (HMHP), which in turn affects the level of O-glucosamine in the eye. O-glucosamine, or O-glucosamine-3-monotrient (OGL) is an oily mineral that the body absorbs from the skin to help protect against free radical damage and lines of deterioration such as crease and elastase. In this way, OGL can be regarded as the “poster child” for an O-glucosamine derivative.
Antibodies respond to the O-glucosamine-3-monotrient molecule (and therefore aminomethylhydrofolate reductase) by targeting a normal mechanism of action and the harmful effects of free radicals. This is, in turn, believed to be an “organophosphate cycling pathway” or O-phosphate/O-glucosamine pathway, in which special proteins regulate the activity of specific pathways, chemical reactions and pathways. But understanding the mechanism by which amtran inhibits the O-glucosamine-3-monotrient molecule has remained elusive.