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sigma receptors? nmda hypoactivity?

Posted by JohnX2 on November 27, 2001, at 22:56:11

Anyone know much about sigma receptors?

I'm studying the pathology of nmda hypo functioning.
Anyways it is very interesting in that there are
areas in the brain where nmda (glutamate exictatory)
receptors stimulate gaba (inhibitory receptor), and
the gaba neuron somehow feedsback to the same
glutame receptor. So if the glutamate receptor is
hypo-functional, the gaba receptors aren't stimulated
and you get "stuck" in this pathological loop that
can lead to brain damage and schizophrenic symptoms.
I'm wondering if this feeback pathway could also
explain medication poop-out mechanisms. Also a
downward spiral to hypoactive nmda receptors would
mean less firing out of an area called the VTA which
shoots dopamine up into very important areas (including
the one that inhibits facial muscles).

The journal Article I am reading by a
Dr. Olney lists the following anti-dotes (Sorry
I don't have the journal article reference
for you all in front of me):

- alpha-2 agonist (tempers acetycholine)
- GabaA agonist (the neurons that are not stimulated
appropriately by hypoactive nmda receptors)
- muscarinic m3 receptors antagonists
(where the excess acetylcholine binds)
- atypical meds like zyprexa,clozapine.

Curiosly these meds relieve(d) my now chronic
tension headaches/bruxism and also
allevate stress and depression:

- Klonopin (GabaA med)
- Serzone ???? Sigma related ? 5ht-2a anagonists
- Zyprexa 5-ht2a antagonist + alpha1 antagonist + ???
- moderate dose of antihistamine chlorphenrimine maleate.
Also really high dose of benadryl
(anti-muscarinic effect???)

Curious about the Serzone? If I recall off the top
of my head it may have some sigma binding properties?

All of these meds also antagonize the problems I
encounter if I take Zoloft or Wellbutrin. On those
meds I would feel emotionally numb, the anti-depressant
would kick in and make me hypomanic (with a return
of emotions), and then it
would poop out leaving me completely emotionally
numb with a massive jaw tension and head pain. Sounds
a lot like a "shizophernic" ping-pong
between positive- >negative psychosis which is
thought to be related to hypo active nmda receptors.

I haven't tried the alpha-2 agonist. There are
alpha-2 adrenorecptors on acetylcholine neurons, and
alpha-2 agonists like clonodine or guanfacine will
attentuate the acetylcholine response. My neurologist
wants me to take Zanaflex (a derivative of Clonodine)
to treat my headaches. I believe it should have the
same effect as Clonodine with regards to the
acetylcholine path. So this will be an interesting

As a side note, I have experimented a lot with
amino-acids and such and found that DMAE (which
basically gets immediately converted to acetycholine)
*substantially* exacerbates my head pain and
emotional numbing.

Any thoughts? Maybe I'm schizophrenic but don't
know it. But I've always speculated the root of
my medication bizzaro to be dysfunctional alpha-2
feedback receptors (which would explain the
acetylcholine response). The alpha-2 noradrenaline
feedback receptors can get all goofed up if you
are exposed to trauma or repeated stress or a med
screws things up.





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