ChEMBL

There was an interesting news article in the latest Chemistry World (Volume 7, No 1, Jan 2010, p 15) on recent phase III disclosures for Flibanserin (which has quite complex pharmacology - a 5HT1A agonist, a 5HT2A antagonist and weak partial agonism at D4, Flibanserin was previously known by the research code BIMT-17). The recent clinical trials have the headline grabbing activity of potentially showing increase in female libido - labelled as HSDD (or Hypoactive Sexual Desire Disorder). Originally the compound was developed as an antidepressant, and it would appear that since several antidepressants 'decrease' sexual function and so clinicians were primed to look for side-effects on libido (for example, some SSRIs have the ability to treat premature ejaculation). Unexpectedly, Flibanserin showed an increase in libido. So, potentially, with Flibanserin, there is another example of a serendipitous discovery (a nice overview of this area is provided in the OHE book pictured above and referenced below).

There are many drugs of this 'anserin' class of potential drugs (the -anserin stem shows that the compounds have 5HT2 receptor antagonism as a major pharmacological activity (for example,
Adatanserin, Altanserin, Benanserin, Blonanserin, Butanserin, Cinanserin, Eplivanserin, Fananserin, Flibanserin, Glemanserin, Iferanserin, Ketanserin, Lidanserin, Mianserin, Pelanserin, Pimavanserin, Pruvanserin, Ritanserin, Seganserin, and Tropanserin
- some of these are 'old' others 'new'). It would be astonishing if all of these have the same selectivity profile as Flibanserin, and also if Flibanserin has the 'optimal' profile for HSDD. So it is of interest to speculate if HSDD is a potential new indication for all/some of these other -anserins). A cursory view of the literature shows that many of these agents have broad activity across many pharmacologically relevant receptors, and so an interesting question, in the context of 'polypharmacology' is:

• Which subset of -anserins have HSDD activity?
  
• Is it possible to predict the next most similar profile compound to Flibanserin?
  
• Would animal data be of any use in profiling/discovery of such compounds?
  

%T Capturing the Unexpected Benefits of Medical Research
%E C. Pritchard
%I Office Health Economics
%D 2001