Class backwards

December 20, 2018

There is a critical, long-term absence of progress in drug discovery for mental health.  Of the multitude of psychiatric small molecule drugs prescribed in the past century, only two were first-in-class drug discoveries; lithium for the treatment of bipolar disorder in 1949 and Thorazine (chlorpromazine) for the treatment of psychosis in 1950. “Both discoveries were utter strokes of luck, and almost every major psychiatric drug introduced since has resulted from small changes to Thorazine.  It is still not clear why or how any of these drugs actually work, although hundreds of genes have been shown to play roles in mental illness…[without clear insights into mechanism]” (G. Harris, New York Times, 1/22/2010, page A1).  More recently, the uniform failure of all candidate Alzheimer’s disease modifying drug candidates in clinical trials has led to the withdrawal of several big pharma companies from the neuroscience arena.  

 

 

A major reason for this is that both lithium and thorazine, and therefore every major psychiatric drug that followed, act on multiple drug targets throughout the body.  This picture of their action appears to be too mind-blowing for scientists and physicians so it has routinely been dumbed-down to a single receptor (“its a D2 antagonist!) or ratio of two receptors (“its 5HT2A/D2 ratio is X!”).  Could this dumbing down be the reason psychiatric drug discovery has been stuck in a rut for...well forever?

 

Well, Genecentrix does not believe its mind-blowing at all.  With the right tool, its downright simple. Like how impossible it was to sensitively and specifically search the millions of web pages before Google, and how easy it was once Google provided the tool.  And GeneCentrix’ founders invented the tool.

 

Now, researchers at NYU Langone Health have shown how simple it is.  They investigated the curious and unique effects of the antidepressant bupropion (Wellbutrin) with GeneCentrix’ approach.  Bupropion is unique among antidepressants in its effects on sleep, smoking cessation and anxiety. Historeceptomics revealed which of bupropion’s specific drug targets in specific brain tissues were unique to it compared to the usual Prozac type anti-depressants.  The finding might open new avenues towards better antidepressants.

 

 

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