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Re: sigma receptors? nmda hypoactivity?

Posted by JohnX2 on November 28, 2001, at 0:18:00

In reply to sigma receptors? nmda hypoactivity?, posted by JohnX2 on November 27, 2001, at 22:56:11

Binding to the Sigma receptor can cause a
disruption to the nmda response curve.
Zoloft potently binds to the sigma receptor.
Hmmm...I think I am onto something here.

St. John's wort was also an effective anti-depressant,
but had the same problem. If memory serves me
correct it is an nmda antagonist and has sigma
binding properties....

My problems started ~3 yrs ago when I first
developed allergies. The bad headaches I get
are very similar to the horrendous headaches
I get during the key allergy season. So I guess a
m3 targeted anti-histamine may help me (less
cholinergic side effects). Probably want to
stay away from meds that bind to the sigma
receptor. Dampen that acetycholine with a
alpha-2 agonist, and damnit maybe I make it
to home base.

Now what is up with Wellbutrin? Hmm, I'm guess
it substantially potentiates the acetylcholine
response. Need to dig deeper...


> 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?
> Yes/no?
> 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
> experiment.
> 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.
> -john




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