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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 16 of 16. This is the beginning of the thread.
Posted by SLS on February 20, 2009, at 16:50:47
What substances:
1. Act as anticonvulsants?
2. Act as anti-glutamatergics
3. Act as NMDA receptor antagonists?
Thanks.
- Scott
Posted by seldomseen on February 20, 2009, at 19:09:59
In reply to Natural anticonvulsants?, posted by SLS on February 20, 2009, at 16:50:47
I think there is some evidence that ginko biloba extract acts an NMDA antagonist.
At what dose, i don't know.
Maybe do a pubmed search on it?
Seldom.
Posted by desolationrower on February 23, 2009, at 19:51:54
In reply to Natural anticonvulsants?, posted by SLS on February 20, 2009, at 16:50:47
don't have time to do anything but what i can think of but off the top of my head here
(exams the next few days i should get back to) :> What substances:
>
> 1. Act as anticonvulsants?
>
> 2. Act as anti-glutamatergics
>
> 3. Act as NMDA receptor antagonists?
>
> Thanks.
>
> - Scottminerals zinc & magnesium are important to nmda function, deficiency causes problems (but there is an upper limit to the antagonism you can get, they dissociate quicker than something like memantine. you can't take a 10g magnesium version of ketamine dissociative khole trip)
i believe cat's claw has some of the 2&3
huperzine is an nmda antagonist, i forget the type, as well as ACHtr.inhibitor
ibogaine!
taurine, nmda i think, don't cross BBB well
neurosteroids, i think some are proconvulsant, but some are gabaa agonists and allostatic modulators
magnolia bark is probably anticonvulsant, from the GABA side of things (i think all the GABAa subtypes are anticonvulsant?). so, similar gaba drugs like muscimol, kava, etc. theanine probably too. most of these have too short a t1/2 to be useful for this purpose. oh and don't forget about scotch.do you know someone who wants a otc alternative to her lamictal, or you just thinking stuff through?
-d/r
Posted by SLS on February 23, 2009, at 20:38:33
In reply to Re: Natural anticonvulsants?, posted by desolationrower on February 23, 2009, at 19:51:54
> do you know someone who wants a otc alternative to her lamictal, or you just thinking stuff through?
Actually, I am looking for ways to reduce the intensity and perhaps duration of withdrawal syndromes from discontinuing SRIs and BZDs. It would be nice to be able to reduce the suffering of people who want to perform a taper and refuse to use any other drugs to manage the syndrome. I am working under the premise that the discontinuation syndrome from these two classes of medications involve glutamatergic hyperactivity resulting from disinhibition.
- Scott
Posted by desolationrower on February 23, 2009, at 23:01:11
In reply to Re: Natural anticonvulsants? » desolationrower, posted by SLS on February 23, 2009, at 20:38:33
interesting, this is what i know, maybe something new that can help:
in serotonin syndrome one factor is nmda activation because of 5ht2 activation, i think colocalised, i think this might be why memantine blocks ss. there is actually mixed evidence on 5ht2a downregulation with ssris, i came across more studies later today. i think 5ht3 is involved in glutamate efflux (memantine antagonises 5ht3 too). natural 5ht3 antagonists include ginger, korean red ginsing.have you thought about the reverse of proposed first-week anxiety/dysphoria because the increased extracellular 5ht hits the autoreceptors and reduces firing (eg, low 5ht levels and high firing)? this sounds not like ss.
venlafaxine withd was bad it felt like a flu - nausea, headache, vertigo, tinnitus/buzzing (i think this is 'shocks' people describe). tinnitus in particular, and 5ht sensory gating function is thouht to play a role. nausea, 5ht3 is known to be involved.
-d/r
Posted by desolationrower on February 23, 2009, at 23:11:10
In reply to Re: Natural anticonvulsants?, posted by desolationrower on February 23, 2009, at 23:01:11
oh something else i'll throw out...most ADs are mildly epileptogenic...shouldn't withdrawl be anticonvulsive? i'm not up on epilepsy, are you thinking your kindling is analagous to epilepsy kindling or actually a subtype?
-d/r
Posted by SLS on February 24, 2009, at 6:48:00
In reply to Re: Natural anticonvulsants?, posted by desolationrower on February 23, 2009, at 23:11:10
> oh something else i'll throw out...most ADs are mildly epileptogenic...shouldn't withdrawl be anticonvulsive?
I hadn't thought of that. I don't know. The multitude of changes that occur after long-term exposure to these drugs would make it hard to determine which withdrawal effects dominate. Maybe the temporal lobes are protected while the amygdala is kindled.
I did find one interesting paper that reported SSRIs ameliorated alcohol withdrawal. This would make sense if the serotonergic pathways effected by these ADs are inhibitory upon glutamate neurons. Here, the SSRIs are acting more anticonvulsant than proconvulsant.
> i'm not up on epilepsy, are you thinking your kindling is analagous to epilepsy kindling or actually a subtype?
Yup.
You would know the dynamics better than I, but serotonin acts as an inhibitor of many glutamatergic pathways. My guess is the sudden drop in synaptic serotonin as a result of removing an SRI disinhibits these glutamate pathways and allows them to become hyperexcitable and leading to kindling. I think the kindling allows for the withdrawal severity to grow more intense over time, prevents some people from discontinuing entirely, and allows for a persistence of withdrawal symptoms long after the drug is discontinued. I also have a hunch that future withdrawal episodes from discontinuing successive SRIs produces more severe withdrawal syndromes.
- Scott
*******************************************1: Alcohol Alcohol. 2008 Jan-Feb;43(1):15-24. Epub 2007 Oct 12.Click here to read Links
Serotonergic anti-depressants and ethanol withdrawal syndrome: a review.
Uzbay IT.Gulhane Military Medical Academy, Faculty of Medicine, Department of Medical Pharmacology, Psychopharmacology Research Unit, Etlik 06018 Ankara, Turkey. tuzbay@gata.edu.tr
AIM: To review laboratory findings on the effects of anti-depressant agents that interact with the serotonergic system on signs of ethanol withdrawal syndrome in rats. METHOD: Adult Wistar rats received a modified liquid diet to produce ethanol dependence. Signs of ethanol withdrawal, locomotor hyperactivity, stereotyped behaviour, tremor, wet dog shakes, agitation, and audiogenic seizures, were evaluated for the first 6 h of ethanol withdrawal. The effects of the anti-depressants fluoxetine, venlafaxine, escitalopram, tianeptine, and extract of Hypericum perforatum (St. John's wort) (HPE) were examined. RESULTS: Some beneficial effects of fluoxetine, tianeptine, HPE, escitalopram and venlafaxine on ethanol withdrawal signs were observed, ranked as follows: fluoxetine = tianeptine > HPE > escitalopram > venlafaxine. CONCLUSIONS: Tianeptine and fluoxetine seem to be potent pharmacologically active agents on ethanol withdrawal syndrome in rats. Thus, these anti-depressants may be useful in treatment of ethanol withdrawal syndrome in patients with alcoholism. In addition to serotonergic effects, interactions with nitrergic, glutamatergic, and adenosinergic systems may also provide a significant contribution to the beneficial effects of these drugs on ethanol withdrawal syndrome.
PMID: 17934195 [PubMed - indexed for MEDLINE
Posted by garnet71 on February 24, 2009, at 12:22:03
In reply to Re: Natural anticonvulsants? » desolationrower, posted by SLS on February 24, 2009, at 6:48:00
You would know the dynamics better than I, but serotonin acts as an inhibitor of many glutamatergic pathways. My guess is the sudden drop in synaptic serotonin as a result of removing an SRI disinhibits these glutamate pathways and allows them to become hyperexcitable and leading to kindling. I think the kindling allows for the withdrawal severity to grow more intense over time, prevents some people from discontinuing entirely, and allows for a persistence of withdrawal symptoms long after the drug is discontinued. I also have a hunch that future withdrawal episodes from discontinuing successive SRIs produces more severe withdrawal syndromes.
- Scott--------------------------
What are glutamatergic pathways and kindling? I'm not sure I'm understanding what you all are saying here--Could this be related to those of us who have had chronic and severe anxiety after discontinuing these drugs that were initially prescribed for a severe depression? Esp. for those of us who never had this problem pre-xxRI?
Could that explain why these drugs haven't worked/treatment resistance? (Common sense - If the drug (discontinuating effects) has caused the problem, how can it be expected to correct it?)
Posted by SLS on February 24, 2009, at 13:15:35
In reply to Re: Natural anticonvulsants? » SLS, posted by garnet71 on February 24, 2009, at 12:22:03
> You would know the dynamics better than I, but serotonin acts as an inhibitor of many glutamatergic pathways. My guess is the sudden drop in synaptic serotonin as a result of removing an SRI disinhibits these glutamate pathways and allows them to become hyperexcitable and leading to kindling. I think the kindling allows for the withdrawal severity to grow more intense over time, prevents some people from discontinuing entirely, and allows for a persistence of withdrawal symptoms long after the drug is discontinued. I also have a hunch that future withdrawal episodes from discontinuing successive SRIs produces more severe withdrawal syndromes.
> - Scott
>
> --------------------------
>
> What are glutamatergic pathways and kindling?The most pervasive stimulatory neurotransmitter in the brain is glutamate. A pathway whose neuron's use glutamate is said to be glutamatergic.
Kindling is like what happens in epilepsy. The more seizures you have, the more frequent and severe they become. The neurons become more hyperexcitable over time and are said to be kindled - as in fire.
> I'm not sure I'm understanding what you all are saying here--
I wish I understood why no one is paying any attention to this theory. It has already been established that a similar thing is occurring with alcohol withdrawal. Using anticonvulsants has been proposed as way to lessen the severity of the withdrawal syndrome, something that I had already suggested. To brag just a little, I came up with this concept independently of those whom had proposed kindling for alcohol. I should send a letter to Robert M. Post at the NIMH to see what he has to say. I'm pretty sure he's still around, despite having had a heart attack. He introduced kindling theory to mental illness.
http://www.dr-bob.org/babble/wdrawl/20050214/msgs/460726.html
> Could this be related to those of us who have had chronic and severe anxiety after discontinuing these drugs
Yes. According to my theory, such a thing is possible.
> Could that explain why these drugs haven't worked/treatment resistance?
Of this, I am not so sure. I think this has more to do with dysregulated receptor feedback loops and possibly altered gene expression via disturbed second messenger systems.
- Scott
Posted by garnet71 on February 24, 2009, at 18:25:01
In reply to Re: Natural anticonvulsants? » garnet71, posted by SLS on February 24, 2009, at 13:15:35
Scott-you need to write a paper about your theory. You don't have to have your degree to write a research paper, or to even have it published. You are still in school, right? This is what you need to do-contact those who have done research needed to support your theory, and those from professional organizations (NIMH, for ex.) using your school email address. Tell them you are facilitating research and that you need more focused information (to support your theory). Especially with the government, there are specific liaisons for students/researchers to contact for info. In exchange for offering you information, they will most likely ask for a copy of your final paper. You should write, develop, and share your theory. You never know who may take interest or if it will get published. I've read of more than one instance where someone unknown has made a breakthrough in theory, but they were not given credit becaues years later, some well-known researcher published it first. Later, it was proven the unknown had already solved the problem or developed the theory.
This is not grandiouse thinking; in conducting my current research, I couldn't believe the level of people who want a copy of my findings (even after I tell them I'm an undergraduate student, that this is my first research project, and I'm not affiliated with any think tank/research org). This is pretty standard among researchers--sharing information; give and take. Quite possibly, the person you are sharing your findings with may become interested in your project, and things will develop from there.
For this specific issue--I can't think of why institutions would want to expend resources to research this topic. Who is going to fund it? Certainly not the government or the drug companies. Unless in doing so, they wish to develop a drug for "SSRI Discontinuation Syndrome", which will become a new syndrome added to the list of new syndromes (some caused by drugs). My two cents, or two dollars.
Posted by myco on February 25, 2009, at 21:18:07
In reply to Natural anticonvulsants?, posted by SLS on February 20, 2009, at 16:50:47
I began using scullcap (Scutellaria lateriflora) tincture recently in place of temazepam for relaxation and sleep induction (actually works very well in a high dose). It's also been shown effective in studies for reducing symptoms of benzo withdrawal. I believe chairman mao mentioned this before.
Posted by Netch on February 26, 2009, at 11:13:30
In reply to Natural anticonvulsants?, posted by SLS on February 20, 2009, at 16:50:47
Vitamin D is an AC
Posted by SLS on February 27, 2009, at 9:21:25
In reply to Re: Natural anticonvulsants? » SLS, posted by Netch on February 26, 2009, at 11:13:30
Thanks guys.
It looks like we are putting a nice list together here.
- Scott
Posted by desolationrower on March 13, 2009, at 21:35:40
In reply to Re: Natural anticonvulsants? » SLS, posted by garnet71 on February 24, 2009, at 12:22:03
oh, don't know how i forgot about this one:
ketogenic diet.
there are probably some identical pathways to benefits from fasting, but obviously for full anticonvulsant benefit you need it constantly). the thing that sucks about ketogenic diets is its a bit harder to gain muscle (well, and you can't eat lots of tasty food), and you can't train quite as hard. but not a huge drawback. Also until you adapt you can feel crappy, which means it might take a few weeks before you would actually want to drop the ssri, since that ALSO will make you feel like sh*t. I've never done the diet, it woudl probably be mostly some low-carb nut varieties and coconut and olive oils with salad leafy greens, with some meat.
i think the anticonvulsant effect is from one of the ketones directly, so it wouldn't take too long to become 'effective' but i haven't looked into it too closely.
-d/r
some interesting things about about ketosis though. for instance:
Med Hypotheses. 2007;68(2):268-71.
Low-carb diets, fasting and euphoria: Is there a link between ketosis and gamma-hydroxybutyrate (GHB)?Brown AJ.
School of Biotechnology and Biomolecular Sciences,
The University of New South Wales, Sydney 2052, Australia.
Med Hypotheses. 2007;68(2):268-71.ABSTRACT
Anecdotal evidence links the initial phase of fasting or a low-carbohydrate diet with feelings of well-being and mild euphoria. These feelings have often been attributed to ketosis, the production of ketone bodies which can replace glucose as an energy source for the brain. One of these ketone bodies, beta-hydroxybutyrate (BHB), is an isomer of the notorious drug of abuse, GHB (gamma-hydroxybutyrate). GHB is also of interest in relation to its potential as a treatment for alcohol and opiate dependence and narcolepsy-associated cataplexy. Here I hypothesize that, the mild euphoria often noted with fasting or low-carbohydrate diets may be due to shared actions of BHB and GHB on the brain. Specifically, I propose that BHB, like GHB, induces mild euphoria by being a weak partial agonist for GABA(B) receptors. I outline several approaches that would test the hypothesis, including receptor binding studies in cultured cells, perception studies in trained rodents, and psychometric testing and functional magnetic resonance imaging in humans. These and other studies investigating whether BHB and GHB share common effects on brain chemistry and mood are timely and warranted, especially when considering their structural similarities and the popularity of ketogenic diets and GHB as a drug of abuse.
Posted by Sigismund on March 13, 2009, at 23:39:56
In reply to Re: Natural anticonvulsants?, posted by desolationrower on March 13, 2009, at 21:35:40
That might be why my nutritional doctor never stops telling me I don't eat enough protein.
Posted by fairn on March 17, 2009, at 3:17:55
In reply to Re: Natural anticonvulsants? » desolationrower, posted by Sigismund on March 13, 2009, at 23:39:56
nmda antags:
Cyperus articulatus,
searsia, danshen, curcumin,glutamate release inhibitors:
cyanocobalamin, D-serine,
phosphatidylserine,affect glutamate synthesis/metabolism
L-canaline, phenylsuccinate,
orthovanadate, vanadyl sulphate,
quinacrine, chinidine, chininei think i read resveratrol has an effect on glutamate release in the hippocampus and ive noticed taking it prevents anger outbursts in me which ive come to believe are caused by the release of glutamate good luck!
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