The Corpus Callosum

The Early Years

Note: this post involves a very small amount of self-disclosure.
 That is a bit unusual.

My father is also a psychiatrist.  He told me once about his
education in psychopharmacology.  A guy got up to lecture,
identified himself as the “drug doctor,” and gave a lecture on
psychopharmacology.  In fact, he gave a series
of
lectures…about five, total.  

That was in the early to mid 1950′s.  What did we have back
then?  Basically two things: uppers and downers.  

By the mid 1980′s things had changed.  We knew about
neurotransmitters and receptors.  I distinctly recall a
lecture
in which the professor semi-jokingly said that he was going to explain
neurotransmission using a series of slides.  One slide
detailed what was known about the synthesis of the transmitters.
 The next showed how the molecules were packed into vesicles,
the next how the vesicles released the molecules into the synapse, and
the next showed how the transmitter binds to the receptor.
 With a flourish, he put up the next slide, which looked
something like this:

i-b1b51e148073a1c890dd6078304b72bd-Slide-1.jpg

(Remember, this was before Powerpoint)


i-e91196d05aad33f915406c278cb539c3-Slide-2.jpg

That was sort of a joke, and everyone sort of laughed.  I’m
sure
you know the kind of laugh.  Anyway, it really did sum up the
state of knowledge at the time.  Yeah, we knew there were
second
messengers, and we knew that transcription and translation were
involved somehow, sometimes.  And depolarization etc.
 

Now, we are starting to get a sense of what the “something” is that
happens.  But only a hint, really.  Sometimes it
seems as
though we are really making progress; other times it seems hopelessly
complex.  Sometimes that complexity is discouraging.
 But
then I remember, it is the damnable complexity of it that attracted me
to the field in the first place!  With the rapid increase in
knowledge from “something happens” to truly useful neuroimaging,
receptor assays, genetics, and what seemed to be a gushing pipeline of
new pharmaceuticals…

Ironically, it may turn out that things like rTMS are the next big
thing.  

I am not happy with the current state of affairs in pharmaceutical
discovery, or development, but the only improvements I could see would
cost an awful lot of money and take a lot of time.  

Which leads me to venture an opinion.  I think we need to pull
back a bit from looking for the next blockbuster drug, and spend a few
more years, or decades, on basic research.  It’s just a gut
feeling, but The way things are going right now, at least with respect
to antidepressants, we seem to be loosing steam.

Comments

  1. #1 Hyperion
    March 1, 2007

    On the other hand, the search for the next blockbuster drug could lead to more knowledge. For instance, suppose that it’s discovered that a drug that affects an entirely different system (ie non-catecholaminergic, non-serotonergic) is effective in treating depression. All of a sudden, there is suddenly a large amount of money that will be invested in figuring out exactly why, I don’t know, acetylcholine or melatonin or something else is involved in depression or mood-regulation.

    Or, for that matter, it might make sense for pharmaceutical companies to do more research into that “something happens” area, to see if there is the possibility of getting a similar (or perhaps better/more efficient) effect of a current drug by altering the down-stream effects (ie using a 5-HT agonist instead of an SSRI) or the upstream effects (ie targeting the presynaptic axon terminal to induce efflux rather than using an agonist at the post-synaptic dendrite receptors).

    Granted, I think it’d be great to be able to take a group of volunteers, repeatedly shoot them up with radio-labelled ligands of all the major neurotransmitters, and put them in SPECT scan while they go through a number of different activities, but that’s probably just not going to happen.

  2. #2 Greg P
    March 1, 2007

    And yet, we’re still stuck back in those unknowing times, without knowing it.
    Yes we have more detail, we have more believable data now (we’re looking at what happens inside cells instead of monitoring changes of things in CSF — how crude is that?!), but there is still a lot of presumptiveness about what it means or what the meta-information is.
    We may understand that a given psychopharmacologic drug results in certain chemical changes, but are these the only changes? What haven’t we measured? And we’re still stuck with an interconnected system, so we may think that a change of chemical in this structure is the important event, but maybe it’s the scattered or magnified effect of those cells with their connections that really causes what we want to happen.
    This is going to remain complicated for the foreseeable future.