Old drugs, new tricksBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d741 (Published 09 February 2011) Cite this as: BMJ 2011;342:d741
- Allen F Shaughnessy, associate program director
- 1Tufts University Family Medicine Residency at Cambridge Health Alliance, Malden, MA 02148, USA
A meta-analysis last year linking aspirin to reduced death rates from certain types of cancer signalled the latest reinvention of this well established drug.1 Developed as an analgesic, greater understanding of its properties has led to it being used to treat stroke and reduce the risk of cardiovascular disease, and it has also been suggested to help prevent pre-eclampsia and dementia.
Aspirin is just one of many drugs that have found new uses, some before they even get to market (table⇓). Raloxifene, for osteoporosis, was a failed oral contraceptive found to increase bone density. The antidepressant fluoxetine flunked hypertension trials but affected mood. The erectile dysfunction treatment sildenafil was ineffective for angina. All three medicines were repurposed to great effect.
Discovering new uses for old drugs offers great promise for quickly bringing new therapeutic options to patient care; the lag between drug discovery and availability, often 10 years or longer, can be shortened by dusting off drugs already marketed and repurposing them. But the discoveries are not simply down to serendipity. New uses are increasingly being discovered not by pharmacologists but by computer scientists in university departments of computational drug discovery or biomedical informatics.
Serendipity and science
Many of the new uses result from better understanding of the drugs’ method of action. Sildenafil, for example, has its roots in zaprinast, an analogue of theophylline that was never marketed but investigated as a treatment for allergy. The drug was also found to potentiate the effect of nitrates by inhibiting breakdown of cyclic guanosine monophosphate (cGMP), an intracellular messenger that causes vasodilatation and hypotension. Although the drug was promising in laboratory studies, its results in angina were disappointing, but some men reported an increase in erectile function. Pursuing …