Posted by JohnX2 on November 29, 2001, at 21:04:37
In reply to Medlib - Have you ever tried Remeron + Buspar ?, posted by SLS on November 29, 2001, at 18:03:58
Hi Scott,
I hope I'm not speaking out of turn.
Remeron = alpha-2 antagonist
Buspar = alpha-2 antagonistIsn't this bad from your experience?
Neither med made my facial pain worse, which
I believe is a function of dopamine firing
from the main pool in the VTA. But the
Remeron made me anxious.BTW, I'm currently taking 150 mg Lamictal
+ 5 mg Zyprexa + 6 mg Klonopin +
+ secret sauce of 8 mg BID sustained release
chlorpheniramine maleate.I don't know why, but I have discovered
serindipidously that the anti-histamine releaves
my tension headaches *and* my depression and
my akathasia (inability to sit still). My
tolerance to simple stimulants like caffeine is
gone, as well as my tolerance to alcohol.
In fact I felt after drinking my usual run
of caffeine today that I had *too much* dopamine
running through my body. But, I wasn't manic.
Normally caffeine poops out quickly.The only thing I can think of is the fact that
my meds are attacking nmda hypo-functioning.
The chlorpheniramine is a potent m3 muscarinic
antagonist, which can block excessive
acetycholine in the extrapyramidal path
that is connected to alpha-2 noradrenaline
heteroreceptors on the acetylcholine neuron
(the noradrenaline is from the locus coerulus).Read US Patent 5,902,815. Look at figure 1.
There are many nmda receptors that
activate gaba neurons. Those gaba neurons feed
back into the nmda receptor. So a goof up in
this little loop could cause pathological nmda
hypo-functioning. I like the nice picture of
this feeback loops for dummies like me in
those patent disclosures of meds to treat
nmda hypo-functioning (figure 1).When I was reading a paper by Dr. Olney on the nmda hypofunctioning
theory of shizophernia, I found some interesting
conclusions. One suggestion to attack this was
an alpha-2 agonist, which you seemed to be curious
about in your earlier posts since you thought
the alpha-2 antagonists made things worse.
The alpha-2 agonist would decrease the acetycholine
transimission along that pathway. Another approach
is to block the m3 receptors the acetylcholine touches
(which is what my anti-histamine does). Zyprexa
also has the right ingredients to treat nmda
hypofunctioning and seems unlikely to cause TD
based on what I was reading. A third approach
is to use a GabaA medication (klonopin).
It is curious that every approach has helped
to relieve my tension headaches which I believe
to be related to hypo-dopaminergic state. I have
also seen references in Olney's work suggesting
that Lamictal can balance this path with an
unknown mode of action (probably nmda buffering).My depression is in some ways similar to
"negative psychosis" in schizo. Anhedonia,
blunted emotions. A lot of dysthymics have made
that same conclusion.Lamictal was the 1st med to cure my major depression
and it also gave me a "short lived complete depression
relief" that pooped out like always happens to me.My neurologist wants me to take Zanaflex
(tizanidine) for my headaches. From my reading,
this is a centrally activating
alpha-2 partial agonist derived from Clonodine
without the hypotension side effects.Some people have overly sensitive
alpha-2 autoreceptors from chronic stress or
trauma, and a partial agonist
would mediate the noradrenergic transmission much
like buspar 5ht-1a partial agonism mediates
serotonin. Anyways, guanfacine (Tenex) or
tizanidine (Zanaflex) or Clonodine (Catapres) can
all help to mediate the very sensitive noradrenergic
paths in the brain. I think the anti-convulsants
don't always work too well in these cases. Anyways,
my expectation is that I can swap the anti-histamine
for Tenex of Zanaflex and get the same results
with less side effects. At a higher dose both
of these meds have side effects consistent with
muscarinic receptors (urinary retention,dry mouth,
etc). It seems your list of responsive meds were
primarily noradrenergic tricyclics, correct?
Do you think the muscarinic effects may be
helping those meds? Also, the alpha-1 antagonism
may be helping as this generally reduces firing
of serotonin neurons and coupled with 5ht-2a
antagonism or 5ht-1a agonism will increase burst
firing from the VTA dopamine pool to counteract
a nmda hypofunctioning state that would lead to too
little dopamine. Ok, I admit, a lot of speculation
on my behalf....I'm wondering how one would do with a noradrenergic
buffering med like Tenex of Zanaflex combined
possibly with a nmda buffer like memantine and/or
Lamictal. Add to this a good anti-depressant.???I have also pondered the effect of adding
topomax to lamictal as topomax works independantly
on GabaA and AMPA receptors, while lamictal
mainly works the NMDA receptors. This may also
stabilize those feedback loops if dosed
correctly.There are also theories related to depression
being induced by acetylcholine-noradrenaline
imbalances...curious.Any thoughts?
regards,
John> Dear Medlib,
>
> I hope you stop by here every now and then to lurk. I posted something addressed to you a few weeks ago, but I forget what. Anyway, a thought occurred to me the other day while I was eating a steak at the local diner. Have you ever tried combining Remeron and Buspar? The steak sucked, by the way.
>
> Geodon = 5-HT2 antagonism + 5-HT1a agonism + DA2 antagonism.
>
> Stip away the offensive EPS DA2 antagonism:
>
> Remeron = 5-HT2 antagonism
> +
> Buspar = 5-HT1a agonism
>
>
> - Scott
poster:JohnX2
thread:85548
URL: http://www.dr-bob.org/babble/20011123/msgs/85557.html