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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by Sean on April 21, 2000, at 13:19:10
Scott - this is a fun post! I was just a tad
less than excited about the article in Brain
Research concerning SSRI's/MDMA brain changes...> Dear Sean,
>
> This is a great post.
>
> I agree with you that it is not a good idea to extrapolate the observed phenomenology of tricyclics to the SSRIs.
>
> I have a few questions for you. I am really not sure about this stuff - I am not trying to be argumentative.
>
> > Well, here's what I understand (from Cooper, Bloom,
> > and Roth's Biochemical Basic of Neuropharmacology):
>
> Has this book been written recently?It's the seventh addition, 1996. I'm sure some
things have changed since then.
>
> > - chronic presence of SSRI's decreases the responsiveness
> > of the 5-HT1a autoreceptors and the function of
> > terminal 5-HT autoreceptors. TCA's produce no
> > observable change in these structures
>
> Are these 5-HT1a autoreceptors presynaptic?I believe so. Somatodendritic.
>
> > - chronic presence of TCA's increases the responsiveness
> > of the POST-synaptic 5-HT autoreceptors
>
> What subtype of receptors are these?
>
> Are they inhibitory? Are they somato-dendritic?They are not somatodendritic and I think they are
not inhibitory in the “re-uptake” sense, but are kind
of like the "end target" of synaptic transmissions. My
understanding is that by increasing the sensitivity
and turnover on the "receiving" end (up regulation?)
that the equilibrium of the autoreceptors is disturbed,
which then causes a homeostatic shift in serotonin
production and a net increase in transmission.But the SSRI's, in my crude understanding, increase
serotonin more directly by down regulating re-uptake
and making more serotonin available. This is closer
to what MAOI's do and probably explains the similarity
of sexual side effects and specific disorders which
respond well to both classes of drugs.
> Are postsynaptic 5-HT1a autoreceptors inhibitory
upon the induction of an action potential
when stimulated?I can't tell from this book. What would this mean?
> Would this tend to reduce the activity of these pathways?
Don't know. My guess is that by having a drug
clogging-up pre-synaptic receptors a chronic basis,
the production and genetics of serotonin production are
altered and give rise to the changes in morphology
described in the Brain Research article.> Do any other 5-HT receptor subtypes act as
postsynaptic autoreceptors?I don't know. There are at least 15 different subtypes, probably
more as serotonin receptors are very heterogeneous. I’m still
learning about this stuff. It’s pretty arcane.>
> > In each case, net 5-HT neurotransmission is increased,
> > so it is correct to say "TCA's affect serotonin."
> > But the effect is produced by an observably different
> > mechanism. ECT also increases the post-synaptic
> > sensitivity of 5-HT receptors which is interesting
> > in the sense that profound melancholia often responds
> > to TCA's or ECT but not always SSRI's.
>
> > There is some evidence that TCA's with a substituted
> > tertiary nitrogen (amitriptyline and imipramine)
> > do directly bind reuptake in the way SRI's do, but
> > not in the proportion or degree of the SRI's.
>
> How does the serotonin reuptake inhibition
of chlomipramine (Anafranil) compare to the
SSRIs in degree?I had this chart at one point which listed serotonin
affinity between a number of antidepressants across
classes. I can't remember if Anafrinil was on there.
I do remember the SRI’s being many hundreds of
times more potent at blocking re-uptake. I think
some were many thousands of times more powerful.
>
> > I don't mean to be stiring things up here, but I
> > simply do not accept the argument that historical
> > experience with TCA's can be used as direct evidence that
> > SSRI induced changes in neuron morphology are not
> > worthy of some measured concern.
>
> I agree. Who said this anyway? This is silly.
???
> > Perhaps what we should accept is that there is a
> > degree of the unkown in psychopharmacology. Since
> > the first generation of SSRI's were created, many
> > subtypes of serotonin receptors have been discovered
> > and cloned. Drugs which act preferentially to these
> > subtypes may not have the same effects as the current
> > generation of drugs. And then there are entire classes of
> > neuropeptides which await exploration, so the current
> > meds are like shifting, ephemeral frames in some
> > movie about the story of our understanding of the
> > brain. I think we're still in the first scene of
> > the film...
>
> Oh yeah, big-time. I am encouraged by what
I see. Perhaps there is just a hint of light visible
in the black box.Yes. We live in exciting times and I’m very thankful
for it. The black box is an interesting metaphor
for both depression and what we don't know about
the brain...
>
> > As far as the "corscrew neurons" debacle, how would everybody
> > feel if scientists did NOT explore the reasons
> > behind it?
>
> What is this all about?Did you see the Brain Research paper? I can dig
it up off the web and send it if you want.Thanks for your interest in this stuff. It is super
abstruse, but somehow therapeutic for me. It helps
organize my “secondary suffering” around medication
issues. I want to know all I can, from my personal history
to my genetic background. Every little bit helps...
Posted by Scott L. Schofield on April 21, 2000, at 13:30:42
In reply to Scott Schofield - did you read this (SSRI's)..., posted by Sean on April 21, 2000, at 13:19:10
Hey Sean,
Thanks for writing.
> > > As far as the "corscrew neurons" debacle, how would everybody feel if scientists did NOT explore the reasons behind it?> > What is this all about?
> Did you see the Brain Research paper? I can dig it up off the web and send it if you want.
That would be great. Thanks.
> Thanks for your interest in this stuff. It is super abstruse, but somehow therapeutic for me. It helps organize my “secondary suffering” around medication issues. I want to know all I can, from my personal history to my genetic background. Every little bit helps...
I think I know where you're coming from. :-) :-(
Thanks again.
- Scott
Posted by KarenB on April 21, 2000, at 13:38:18
In reply to Scott Schofield - did you read this (SSRI's)..., posted by Sean on April 21, 2000, at 13:19:10
> Thanks for your interest in this stuff. It is super
> abstruse,
ABSTRUSE?? Is that a custom blend of abstract and obtuse...or do I need to just shut up and get a dictionary?Karen
Posted by Scott L. Schofield on April 21, 2000, at 13:53:27
In reply to Re: Scott Schofield - did you read this (SSRI's)..., posted by KarenB on April 21, 2000, at 13:38:18
> > Thanks for your interest in this stuff. It is super
> > abstruse,
>
>
> ABSTRUSE?? Is that a custom blend of abstract and obtuse...or do I need to just shut up and get a dictionary?
>
> Karen
Hey Karen - Even if we weren't able to find it in a standard dictionary, we could always enter it into our own as Psycho-Babble.
------------------------------------ab·struse (b-strs, b-)
adj.Difficult to understand; recondite
------------------------------------
Now I'm going to have to look up the word "recondite". I shutter to think how many more words I'll have to look up once I find it.
:-)
Please don't shut-up. You're fun.
- Scott
Posted by KarenB on April 21, 2000, at 14:26:15
In reply to Re: Scott Schofield - did you read this (SSRI's)..., posted by Scott L. Schofield on April 21, 2000, at 13:53:27
> > > Thanks for your interest in this stuff. It is super
> > > abstruse,
> >
> >
> > ABSTRUSE?? Is that a custom blend of abstract and obtuse...or do I need to just shut up and get a dictionary?
> >
> > Karen
>
>
>
> Hey Karen - Even if we weren't able to find it in a standard dictionary, we could always enter it into our own as Psycho-Babble.
>
>
> ------------------------------------
>
> ab·struse (b-strs, b-)
> adj.
>
> Difficult to understand; recondite
>
> ------------------------------------
>
> Now I'm going to have to look up the word "recondite". I shutter to think how many more words I'll have to look up once I find it.
>
> :-)
>
>
> Please don't shut-up. You're fun.
>
>
> - ScottThanks, Scott - I needed that today:)
K
Posted by Sean on April 21, 2000, at 17:26:15
In reply to Re: Scott Schofield - did you read this (SSRI's)..., posted by KarenB on April 21, 2000, at 14:26:15
Hee hee! ya know, the word abstruse is just so... abstruse!
I always eschew obsfucation whenever possible too.
sEaN.
> > > > Thanks for your interest in this stuff. It is super
> > > > abstruse,
> > >
> > >
> > > ABSTRUSE?? Is that a custom blend of abstract and obtuse...or do I need to just shut up and get a dictionary?
> > >
> > > Karen
> >
> >
> >
> > Hey Karen - Even if we weren't able to find it in a standard dictionary, we could always enter it into our own as Psycho-Babble.
> >
> >
> > ------------------------------------
> >
> > ab·struse (b-strs, b-)
> > adj.
> >
> > Difficult to understand; recondite
> >
> > ------------------------------------
> >
> > Now I'm going to have to look up the word "recondite". I shutter to think how many more words I'll have to look up once I find it.
> >
> > :-)
> >
> >
> > Please don't shut-up. You're fun.
> >
> >
> > - Scott
>
> Thanks, Scott - I needed that today:)
>
> K
This is the end of the thread.
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Dr. Bob is Robert Hsiung, MD,
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