Wait, These Drugs Do What?

If I were to tell my mom I just spent a week reading and delving into an article discussing an alternative signaling pathway of the dopamine receptor involving the molecules Akt and GSK, she would probably give me a blank stare, but would smile, nod, and tell me, “That’s nice,” and then promptly change the subject to avoid discussing it further.   In fact, my guess is that this is how most people would respond.  I’m going to tell you a big secret: I don’t really understand it either.  In fact, though there were certainly people that understood better than others, I don’t think there was a single person in our class of senior science majors that would be able to clearly explain the entire article.  This brings me to an important point: in terms of science, we rarely know entirely what we are talking about.  This forms the basis of scientific research—we are always in a quest to understand more.

One of the main applications of the research this article reviewed appears to be in antipsychotic medications.  Many of these are pharmaceuticals which have been on the market for a long amount of time already, but we are still learning more about their mechanisms of action.  This is not to say that these drugs haven’t been evaluated to ensure they meet the minimum safety requirements to be approved for use, but we are constantly learning more about how they actually work.  For example, the utility of lithium in the treatment of bipolar disorder was known long before it was shown to inhibit GSK3, one of the molecules we studied this week.  Previously, it was only known that lithium modulated dopamine release and blocked its binding to its receptor.  Other antipsychotics which have also been used for a significant amount of time are also seeing similar discoveries.  They were known to block dopamine receptors, but it was previously unknown that they also activated Akt which leads to the inhibition of GSK3.  This pathway has not been explored nearly as much as others, especially the dopamine pathway that involves cAMP and PKA (two very well-known and highly-studied molecules in biochemistry).

Though it is easy to get bogged down in the technical details of these pathways, my point is this:  the development and investigations upon pharmaceuticals is far more complex than most realize.  Countless medications have been developed on the basis of observing the effect of some toxin in nature, and then working backwards to figure out why the toxin has that effect and how it can be manipulated and harnessed to treat disease.  We often know that a treatment works, but we are not always one-hundred percent sure as to why.  We become empowered, however, as we learn more and more.  For instance, the pathway we studied this week appears to be at play in schizophrenia, Parkinson’s disease, and several other neuropsychiatric disorders.  Though treatments have been developed for these in the past by targeting dopamine receptors, knowledge of this pathway opens up new avenues to explore in treating these conditions while potentially treating these more specifically, and hopefully developing treatments with fewer adverse side effects.