Posted by JohnX on October 8, 2001, at 2:00:11
In reply to Re: baclofen and memantine and friends » JohnX, posted by SLS on October 7, 2001, at 10:04:13
> > Hi.
> >
> > Been a long while since I've posted to
> > this newsgroup. In case anyone remembers me
> > I had been suffering from intractable dysthymia/
> > pseudo-bipolar II disorder with strange reactions
> > to medications centering around somewhat bizarre
> > headaches and bruxism with hypo-mania and/or severe
> > emotional numbing.
> >
> > Anyways, I'm doing fairly well on Lamictal and
> > have since added a dose of zyprexa (5 mg/day) but
> > still struggle with klonopin addiction as this is
> > the only thing that releives pain in my head and jaw.
> >
> > I've made some interesting observations regarding
> > my pain and how it is affected by medications and
> > have since seen a decent neurologist who suggested
> > taking the anti-spasmodic Baclofen (a GabaB agonist).
> > I've tried everything in the book and he was
> > a little skeptical that he could help, but I had
> > never gone this route. Interestingly, what I learn
> > about Baclofen is somewhat in-line with my thoughts about trying the medication memantine.
> >
> > I'm wondering if anyone has experience with this Baclofen medication? I was initially trying to talk my pdoc doctor into letting me import memantine (a non-competitive nmda antagonist, listed as a muscle-relaxant in the Merck index), because it seemed to have a lot of qualities that may alleviate my problems. But since I've looked into this Baclofen, it has a lot of the same properties in regards to its anti-spasmodic activity and also interesting properties possibly relavent to my scenario (addiction,
> > tolerance, mood-swings, twitching, blah, blah..).
> >
> > Here's my poop:
> >
> > - On the anticonvulsants, Lamictal being the best,
> > I get relief from spasms and it seems to do a good
> > job of relieving my major depression at 150 mg/day.
> > I'm still dysthymic. Above 150 mg/day I get a
> > severe pressure in my head
> > (which I have experienced on other meds).
> > My new pdoc had me augment the lamictal with
> > trileptal and it instantly made the pressure in my
> > head really bad, so I punted it.
> > - The following meds "releave" the severe pain in my
> > head and jaw (which can get locked tight):
> > - Serzone (completely , punted due to drowsiness)
> > - Adderall (although I grow tolerant after 2-3
> > days). Klonopin alleviates the Adderall tolerance.
> > But I got trapped with klonopin tolerance. Off
> > of adderall due to manic episodes and physician
> > reluctance.
> > - Klonopin
> > - dextromethorphan (in robotussin-DM).
> > This is a non-competitive NMDA antagonist like
> > memantine, but not good to take in high dose.
> > - large doses of benadryl (diphenhydramine).
> >
> > Crud that makes my pain *bad* usually accompanied
> > by severe emotional numbing:
> >
> > - St. John's Wort,Zoloft,Wellbutrin,
> > bumping the dose of Lamictal.
> >
> > The "Crud" that makes the pain bad also happened
> > to be the most effective anti-depressants. For a short
> > while at the therapeutic dose the powers that be
> > would relieve my depression for a short while (minutes,
> > hours, one time for 2 days), and then I would snap
> > into severe emotional numbing and pressure in head
> > and jaw.
> >
> > (Information overload).....
> >
> > I found my experience on Aderrall interesting as
> > it relieved my pain and depression, unlike anything
> > else. I also found it strange that I develop rapid
> > tolerance to it stand alone and no tolerance problem
> > with Klonopin. After researching SSRI induced bruxism,
> > and with some feedback from others, I found that
> > the area of the brain that modulates the facial muscles
> > is in the prefrontal cortex. For schizophrenics (not
> > me) a "negative" psychosis (severe emotional blunting)is thought to be associated with hypo-dopamanergic
> > frontal cortex. Curiously I see a pattern, meds that
> > treat "negative psychosis", i.e. increase dopamine
> > up in that area, also relieve my pain. This would be
> > 5ht-2 antagonists, dopamine agonists, klonopin (which
> > can relieve dopamine receptor supersensitivity).
> >
> > So I'm hoping zyprexa helps me without the serzone
> > drowsiness that caused me to crash my car, but the
> > jury is still out. I would prefer a "cleaner" alternative, and it seemed that memantine was an interesting route. I got the pdr from NTII (the company
> > sponsoring its clinical trials in the US), and it
> > listed a zillion treatments: -alzheimers,parkinson,anti-addiction/tolerance,anti-dyskenesia. Curiously it also listed "pressure in the head" as a possible side effect. When I asked about this I found that it could be caused by an osmotic imbalance which would induce water retention in the brain (which has this darn skull around it giving the pressure no-where to relieve itself). Hmm. Anyways this is also symptomatic of cerebral ischema which memantine supposedly treats (so I guess the side effect potential for pressure in the head is like when they list depression as a side effect in the pdr of
> > an anti-depressant).
> >
> > Man, just looking for an end to this saga.
> > Am I on the right track, or am I neurotic?
> >
> > -John
>
>
> Hi John.
>
> It will take me quite awhile to get through your post, due to how difficult reading is for me. Fortunately, so is not the case for writing - even though this might at first seem incongruous. So I figured I'd throw out a few thoughts now while I still have them.
>
> The Zyprexa seems to be a good idea in light of your possitive response to Serzone - 5-HT2 antagonism. Perhaps Remeron might be helpful at medium dosages. An ideal drug might be ritanserin or ketanserin. They are pretty selective 5-HT2 antagonists that I think are devoid of sedative effects - although I would have to double-check. Unfortunately, they are drugs without an indication. They make great biological probes, but I don't think any drug company is interested in developing them for marketing. Perhaps you can find someone who is using it on an open label basis.
>
> Regarding memantine and the ubiquitious 3 day period of psychostimulant effectiveness before tachyphylaxis rears its ugly head: I consider AndrewB to be enourmously knowledgeable andd insightful when it comes to the uses of various agents that enhance dopaminergic neurotranmission and the treatment of dysthymia. He has a great handle on the dynamics of glutamatergic events, their consequences, and their manipulation. Beyond this, another very important quality that he possesses is that he is an extraordinary observer and reporter. I take as gospel his report that mementine has prevented him from becoming tolerant to the positive effects of Adderal, and that it has afforded him a continuous and smooth response to it. He has also found selegiline 5.0mg to be helpful in treating dysthymia. I believe his cocktail includes amisulpride (a neuroleptic devoid of 5-HT2 antagonism, but very preferential in antagonizing presynaptic DA autoreceptors over those postsynaptic at low dosages), selegiline, Adderal, and memantine. I’m sure after all of my patronizing of him here, he’ll chime in eventually.
>
> I have a few questions. I often get confused about the differences between competitive and non-competitive binding. How are they different, and what are the general differences in the effects they yield? How do they function as the concentration of endogenous ligand increases?
>
> In what ways is baclofen similar to memantine?
>
> Thanks.
>
> Ok. Back to reading a few more sentences of your post. I refuse to proofread this one.
>
>
> Take care,
>
> ScottScott,
I'll make you read more of my drivel for
sadistic pleasure;).I was reluctant to take zyprexa and/or geodon
for a while because I was already having twitching
and didn't want to take anything else that was
"dirty" i.e. could cause TD, etc.Regarding AndrewB, he is extremely knowledgeable and has amazing
deductive thinking and problem solving skills. More importantly
he is a kind human-being. He took a lot of time
out of his personal schedule to help me through a difficult
period about 6 months ago, and for that I will be
forever gratefull. I am very impressed. I work in engineering
and analytical thinking/deductive reasoning are critical
to being successfull in my field. Unfortunately I have
met too many doctors that have to use a formulaic
flow-chart to diagnose a problem and can not use deductive
logic to help the patient tailor their needs according to their
treatment responses.Although I person does not make a clinical trial,
AndrewB's discussions with me offline
generally come to great logical and intellectually
challenging problem solving narratives that I have
never have experienced but with a few really
good physicians.I believe AndrewB was actually taking memantine initiallly for its
neuroprotective potential against TD from the amisulpride.
I should be corrected if I am wrong.
When he mentioned the med to me and I did a background check, I found out about
its anti-addiction qualities and found that fascinating
because of my weird Aderrall poop-out that I have
described, and relayed it to AndrewB.
That gave him the idea to re-start experimentation with
Adderall (or dexedrine). He told me he had given up
on the med (Aderall) prior because of the poop-out
problem.Anyways, I did try to obtain ketanserin (or was it
ritanserin) but it quickly was pulled from the source I was looking into.
Anyways Zyprexa seems to have the qualities similar to
Serzone (5ht-2 antagonism, alpha-1 antagonism).
I have also been taking Remeron and it has helped
my sleep, but not been as effective with my pain
symptoms.
So I always have believed that at a low dose something
like zyprexa may help. I have even seen references to Zyprexa
preventing amphetamine induced hypo-activity in the VTA area
of the brain. There is a tangled web of dopamine feed back as well
as interactions with Gabaergic and glutamate pathways
leading to the sensitization. I have read many
references to Gabaerigic meds like klonopin (and
now baclofen) and also nmda-antagonists (like
dxm,research mx-801, etc) having similar properties
of reducing dopamine receptor sensitization to
opiods and stimulates. And the 5ht-2 antagonists
are likely linked to glutamate release.To answer your questions about antagonists,agonists,
blah, blah. I'll use Inderal vs. Pindolol as an
example (Buspar is interesting too).Inderal is a beta-blocker, it has a binding affinity
at the beta-adrenoreceptor, but *it does not* activate
the receptor. This makes it a pure "antagonist".
Stuff that activates the receptor (nor)adrenaline
is fully blocked.
Pinodolol is actually a "partial agonist" at the
beta-adrenoreceptro sight. It bind to the receptor
and activates it, but it activates it less than if
(nor)adrenaline binds to the sight.I don't remember the exact mechanism behind
memantine but it is well understood and is
"clean". No BS from the manufacturer saying the
"mode of action is unknown". It is a simple
derivative of amantadine (two extra methyl groups
for you chemistry buffs). I believe memantine
mainly prevents toxic glutamate release by blocking
excessive calcium release. From what I understand,
other meds that work on the electrolytes
(like Lamictal), change the electrical potentials
required to fire the neurons. So the neurons may
require more stimulus to fire, but I'm not sure what
the end result is in the actual chemical release from the
neuron in the case of the electrolyte mediating
anti-convulsants.Anyways, baclofen looks like a clean GABAB agonist.
But I have to wonder why a gaba agonist like baclofen
would not be just as addictive as Klonopin? Reportedly
Baclofen is now being used in place of meds like
clonidine to help with benzo withdrawal.This all seems fascinating to me because at the
end of the day the most prominent chemical in the
brain is glutamate. And clean meds that stabilize
it seem logically to be important discoveries. I think
this has potential to solve a lot of problems like
how the body long term adapts to other meds
(anti-depressants, stimulants, pain relievers etc.)ps. I have the german translated version of
the memantine PDR if anyone is interested. I got
it from NTI. Forest labs is betting money on
memantine, because the only other thing they
really have going is a "new and improved" version of
celexa which basically removes one of the stereo-isomers
of the chemical to hopefully get rid of side-effects.
Stereo isomers are chemical chains that have
the same formula, but are mirror images. A lot of
time one of the isomers does all the work and
the other does nothing. Eli-lilly tried this
trick with prozac, and it flopped. Pharmaceutical
makers scrambling to protects $$$$'s from expiring
patents....Sorry to ramble and if any of my commentary
is not pertinent to this news thread let me
know.regards,
-john
poster:JohnX
thread:80511
URL: http://www.dr-bob.org/babble/20011007/msgs/80603.html