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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 36. This is the beginning of the thread.
Posted by Janelle on May 6, 2002, at 4:46:05
I have read that Klonopin and Depakote both work on GABA, but apparently in different ways. I don't understand how each of these meds works on GABA and would very much appreciate it if anyone who knows how they each affect GABA could explain it briefly and as simply as possible. Thank you!
Posted by Ritch on May 6, 2002, at 13:31:00
In reply to What about Klonopin, Depakote and GABA..., posted by Janelle on May 6, 2002, at 4:46:05
> I have read that Klonopin and Depakote both work on GABA, but apparently in different ways. I don't understand how each of these meds works on GABA and would very much appreciate it if anyone who knows how they each affect GABA could explain it briefly and as simply as possible. Thank you!
Janelle,All I know about the differences between Klonopin's and Depakote's effect on GABA is that Klonopin acts at the GABA receptors (like other benzos), whereas from what I understand, Depakote tends to promote GABA synthesis (your brain makes more of it). There are others here that know more specifics, but that's what I understand it to be.
hope this helps,
Mitch
Posted by Janelle on May 6, 2002, at 21:33:02
In reply to Re: What about Klonopin, Depakote and GABA... » Janelle, posted by Ritch on May 6, 2002, at 13:31:00
Thanks for explaining what you know about the differences between Klonopin's and Depakote's effect on GABA ... I have just one follow-up question if you don't mind:
You said that Klonopin acts at the GABA receptors (like other benzos) - what does this mean - what does it *do* at the GABA receptors? Does it do what SSRI's do at their respective receptors, meaning some kind of blockade of GABA reuptake so there would be more GABA flowing in the brain?
I ask because I've been on Klonopin a long time and then had that HORRIBLE reaction/deep depression when I began with Depakote, so I'm wondering if maybe I got a GABA overload since you said that Depakote tends to promote GABA synthesis (your brain makes more of it) and I'm wondering if Klonopin also does something to have more GABA floating in the brain?
Thanks!
Posted by fachad on May 6, 2002, at 21:59:46
In reply to What about Klonopin, Depakote and GABA..., posted by Janelle on May 6, 2002, at 4:46:05
My knowledge is very limited here, but I'll try put out a vauge answer for you.
Klonopin directly activates GABA receptors. It is a real benzodiazapine and is a direct agonist at the benzodiazapine/GABA receptor.
Depokate somehow (?) "enhances" GABA activity, but it is not thru a direct agonist activity like Klonopin.
That's all I know.
> I have read that Klonopin and Depakote both work on GABA, but apparently in different ways. I don't understand how each of these meds works on GABA and would very much appreciate it if anyone who knows how they each affect GABA could explain it briefly and as simply as possible. Thank you!
Posted by Janelle on May 6, 2002, at 22:58:29
In reply to Re: What about Klonopin, Depakote and GABA... » Janelle, posted by fachad on May 6, 2002, at 21:59:46
Okay, you said that "Klonopin directly activates GABA receptors. It is a real benzodiazapine and is a direct agonist at the benzodiazapine/GABA receptor."
What does this mean precisely - by "activating" the GABA receptors does it mean that the Klonopin gets the GABA receptors to release more GABA? (then again, I thought that receptors don't do any releasing of chemicals!)
By being a direct agonist at the benzo/GABA receptor I know (thanks to you!) about the key and lock analogy, so the Klonopin would be the key that fits into the receptor (lock) -- so my question remains - what does the Klonopin actually *do* at the GABA receptor to activate GABA?
I guess I need a brief explanation of the "direct agonist activity" that Klonopin has on GABA!
And you'll be glad to know that all I really wanted to know about Depakote and GABA you answered when you wrote that Depokate somehow (?) "enhances" GABA activity, but it is not thru a direct agonist activity like Klonopin."
I just needed to know that Depakote apparently increases/enhances GABA activity.
So, now I'm theorizing that if Klonopin activates GABA and Depakote does too, I may have had GABA overload from being on both of those meds, or it could be that like others mentioned in my thread, the Depakote unto itself was what plunged me into that horrible depression.
Thanks for answering my follow-up question re Klonopin's action with GABA!
Posted by Ritch on May 6, 2002, at 23:55:26
In reply to Thanks Mitch, a bit more here: » Ritch, posted by Janelle on May 6, 2002, at 21:33:02
> Thanks for explaining what you know about the differences between Klonopin's and Depakote's effect on GABA ... I have just one follow-up question if you don't mind:
>
> You said that Klonopin acts at the GABA receptors (like other benzos) - what does this mean - what does it *do* at the GABA receptors? Does it do what SSRI's do at their respective receptors, meaning some kind of blockade of GABA reuptake so there would be more GABA flowing in the brain?
>
> I ask because I've been on Klonopin a long time and then had that HORRIBLE reaction/deep depression when I began with Depakote, so I'm wondering if maybe I got a GABA overload since you said that Depakote tends to promote GABA synthesis (your brain makes more of it) and I'm wondering if Klonopin also does something to have more GABA floating in the brain?
>
> Thanks!Janelle,
When you have a GABA receptor-specific med like Klonopin (and other benzos) I don't think it increases the levels of GABA, it kind of "fools" the synapses/receptors into "thinking" there is plenty of it around instead (that's what I get out of that anyhow!). However, a med like Gabitril (tiagabine) does block the "reuptake" of GABA and that is a different mechanism and is similar to an SSRI blocking reuptake of serotonin. This results in extracellular GABA building up in the synapse as serotonin would build up in the synapse due to an SSRI, so that would increase GABA, but only in the synapses. Depakote, is supposed to make it chemically more "attractive" for your brain to *manufacture* GABA to begin with (from what I understand). There is an anticonvulsant called vigabatrin that blocks the abiliity of the brain to *break down* GABA, which is similiar in a way to an MAOI antidepressant "fails" to break down serotonin, norephinephrine, etc.. Ooops, I probably have created more questions than I can answer :0
Mitch
Posted by Janelle on May 7, 2002, at 2:26:36
In reply to Re: Thanks Mitch, a bit more here: » Janelle, posted by Ritch on May 6, 2002, at 23:55:26
Are you saying that because a GABA receptor-specific med like Klonopin (and other benzos) kind of "fools" the synapses/receptors into "thinking" there is plenty of GABA around, that being fooled like this, the brain would then lower/stop GABA production?
I thought GABA acts to calm a person, so I thought that Klonopin and other benzos somehow created more GABA in the brain, but not according to what you said!
Maybe my confusion now is that I'm mistaken about what GABA does - do you know and if so, could you also explain it?
Thanks!
Posted by Janelle on May 7, 2002, at 2:38:36
In reply to Re: Thanks Mitch, a bit more here: » Janelle, posted by Ritch on May 6, 2002, at 23:55:26
I should have done the search BEFORE I posted just above to you - sorry.
I did a search on GABA which confirmed that I am RIGHT - it IS a calming thing - it's a non-essential amino acid that has a calming effect.
Thus, my question to you regarding Klonopin and benzos still stands:
Are you saying that because a GABA receptor-specific med like Klonopin (and other benzos) kind of "fools" the synapses/receptors into "thinking" there is plenty of GABA around, that being fooled like this, the brain would then lower/stop GABA production?
Since GABA acts to calm a person, I would think that Klonopin and other benzos somehow create more GABA in the brain, but not according to what you said! Which leads me to also wonder/ask just how do Klonopin and other benzos manage to calm anxiety if they do not increase GABA?
Hmmmmmmm ...!
Posted by Ritch on May 7, 2002, at 8:29:33
In reply to Mitch, update here! » Ritch, posted by Janelle on May 7, 2002, at 2:38:36
> I should have done the search BEFORE I posted just above to you - sorry.
>
> I did a search on GABA which confirmed that I am RIGHT - it IS a calming thing - it's a non-essential amino acid that has a calming effect.
>
> Thus, my question to you regarding Klonopin and benzos still stands:
>
> Are you saying that because a GABA receptor-specific med like Klonopin (and other benzos) kind of "fools" the synapses/receptors into "thinking" there is plenty of GABA around, that being fooled like this, the brain would then lower/stop GABA production?
>
> Since GABA acts to calm a person, I would think that Klonopin and other benzos somehow create more GABA in the brain, but not according to what you said! Which leads me to also wonder/ask just how do Klonopin and other benzos manage to calm anxiety if they do not increase GABA?
>
> Hmmmmmmm ...!
Janelle,Since GABA is an inhibitory ("calming") neurotransmitter, and Klonopin/benzos act at the GABA receptors, I think that it makes the GABA receptor more "sensitive" to what GABA happens to be present thus inhibiting neuron firing more so than it would do otherwise without the receptors being "sensitized". Just a hunch-going on memory-no coffee yet :-)
Mitch
Posted by Ritch on May 7, 2002, at 8:51:46
In reply to Re: Mitch, update here! » Janelle, posted by Ritch on May 7, 2002, at 8:29:33
Janelle
Check out SusanC's post below if you haven't already. The article is very interesting about Depakote.
http://www.dr-bob.org/babble/20020503/msgs/105320.html
Posted by katekite on May 7, 2002, at 13:15:57
In reply to What about Klonopin, Depakote and GABA..., posted by Janelle on May 6, 2002, at 4:46:05
Hi Janelle,
Ok so here's how it works, read thru to the end for new information:
GABA is a neurotransmitter. GABA is the key, it fits into the GABA receptor (lock). GABA receptors are present on the surface of GABA based neurons.
Most GABA based neurons are inhibitory to other neurons. This means when they are activated by GABA, brain activity is slightly inhibited.
This leads to the results of less anxiety, sleepiness, or decrease in seizure (which is extreme overactivity in some part of the brain).
Benzodiazepines such as klonopin are chemicals that bind to a site on the GABA receptor that is NOT the site where GABA binds. (think of it as a big lock) The sites where GABA and benzodiazepines bind are very close to eachother. It is thought that the benzodiazepine binding changes the conformation of the GABA receptor, and this change in shape actually allows GABA to bind more easily.... ie it changes the shape of the lock to fit the key better.
The analogy is instead of jiggling the key in the lock before it turns, it turns smoothly the first time. So basically benzodiazepines are like oil, they lube up the slot where GABA fits.
So with a benzodiazepine like klonopin attached, GABA binds easier and may stay there longer, all of this makes the GABA neuron more likely to be able to send its inhibitory signal.
Hope that helps.
Not sure how depakote works.
kate
Posted by Janelle on May 7, 2002, at 17:34:44
In reply to Janelle! Update here! :-0 » Ritch, posted by Ritch on May 7, 2002, at 8:51:46
Posted by Janelle on May 7, 2002, at 17:36:39
In reply to benzodiazepine mechanism, posted by katekite on May 7, 2002, at 13:15:57
Posted by Janelle on May 7, 2002, at 17:44:12
In reply to What about Klonopin, Depakote and GABA..., posted by Janelle on May 6, 2002, at 4:46:05
I did a quick search and found the following about Depakote and Gaba:
"Although the mechanism of action is not established, its [Depakote's) activity may be related to increased brain levels of gamma aminobutyric acid (GABA). This may also account for its prolactin lowering effects.
Depakote (valproic acid) may also inhibit an enzyme responsible for the catabolism of GABA, potentiate postsynaptic GABA responses, affect the potassium channel or have a direct membrane stabilizing effect."
Based on this, somehow (not sure just how) Depakote does something to enhance the presence of GABA in the brain!
Posted by Janelle on May 7, 2002, at 17:50:40
In reply to What about Klonopin, Depakote and GABA..., posted by Janelle on May 6, 2002, at 4:46:05
Check this out - it actually compares benzos like Klonopin directly to Depakote in their action on GABA! I think I've answered my question! (can you tell I'm just a wee bit excited?!)
"VPA affects the action of GABA (gamma amino butyric acid), similar to agents such as phenobarbital and benzodiazepines. While these sedative hypnotics appear to enhance the postsynaptic action of GABA, VPA appears to increase the amount of GABA available to the CNS. Valproate has been shown (in vitro) to increase GABA levels by increasing the activity of glutamic acid decarboxylase and inhibition of GABA transaminase."
Posted by djmmm on May 7, 2002, at 18:42:05
In reply to Here's something right on Klono vs. Depa and GABA!, posted by Janelle on May 7, 2002, at 17:50:40
Most anticonvulsants manipulate both GABA and sertonin...depakote increases *and* decreases monoamine levels in various specific parts of the brain, also, levels of tyrosine are increased.
The increase in Dopamine is mediated by the activation of 5-ht1a receptors, decreased levels are connected to the GABA-A receptors.
Klonopin mechanism of action (from cp-online):
"Benzodiazepines act at the level of the limbic, thalamic, and hypothalamic regions of the CNS, and can produce any level of CNS depression required including sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and coma. The action of these drugs is mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Central benzodiazepine receptors interact allosterically with GABA receptors, potentiating the effects of GABA and thereby increasing the inhibition of the ascending reticular activating system. Benzodiazepines block the cortical and limbic arousal that occurs following stimulation of the reticular pathways."
Posted by Janelle on May 7, 2002, at 19:30:49
In reply to Re: Here's something right on Klono vs. Depa and GABA!, posted by djmmm on May 7, 2002, at 18:42:05
Posted by JohnX2 on May 8, 2002, at 1:00:17
In reply to What about Klonopin, Depakote and GABA..., posted by Janelle on May 6, 2002, at 4:46:05
> I have read that Klonopin and Depakote both work on GABA, but apparently in different ways. I don't understand how each of these meds works on GABA and would very much appreciate it if anyone who knows how they each affect GABA could explain it briefly and as simply as possible. Thank you!
Here's a paper I dug up on Gaba:
http://www.vcu-cme.org/gaba/gaba2_22.pdf
One should note that there are various types of
Gaba receptors; namely Gaba-A and Gaba-B.Klonopin and most benzos work at the Gaba-A receptors.
Depakote from what I understand has some affinity for the
Gaba-B receptor.John
Posted by Ron Hill on May 8, 2002, at 15:23:43
In reply to Re: What about Klonopin, Depakote and GABA... » Janelle, posted by JohnX2 on May 8, 2002, at 1:00:17
Posted by SLS on May 8, 2002, at 17:08:07
In reply to Hey folks: Look what I found re Depakote/GABA!!, posted by Janelle on May 7, 2002, at 17:44:12
Hi Janelle.
> Based on this, somehow (not sure just how) Depakote does something to enhance the presence of GABA in the brain!
Depakote (valproate) increases the amount of GABA available by inhibiting an enzyme known as GABA transaminase. This mechanism is analogous to how MAO-inhibitors work to increase the levels of the monoamines (DA, NE, 5-HT). Two other drugs I know of inhibit GABA transaminase: the MAOI Nardil (phenelzine) and the anticonvulsant Sabril (vigabatrin).
Depakote also acts to stabilize nerve cell membranes by slowing-down the movement of ions (electrically charged molecules) through sodium channels.
- Scott
Posted by SLS on May 8, 2002, at 17:20:47
In reply to Re: Hey folks: Look what I found re Depakote/GABA!! » Janelle, posted by SLS on May 8, 2002, at 17:08:07
I filled in some more of my chart. Please let me know if you find any errors of misinformation.
http://sl.schofield3.home.att.net/medicine/psychiatric_drugs_chart.html
- Scott
Posted by Ritch on May 8, 2002, at 23:12:33
In reply to Re: Hey folks: Look what I found re Depakote/GABA!!, posted by SLS on May 8, 2002, at 17:20:47
Posted by Ron Hill on May 9, 2002, at 0:04:41
In reply to Re: Hey folks: Look what I found re Depakote/GABA!!, posted by SLS on May 8, 2002, at 17:20:47
Scott,
Nice table. Do you store your web page(s) on your own server or do you rent server space?
-- Ron
Posted by SLS on May 9, 2002, at 0:30:56
In reply to Re: Nice table Scott » SLS, posted by Ron Hill on May 9, 2002, at 0:04:41
> Scott,
>
> Nice table. Do you store your web page(s) on your own server or do you rent server space?
>
> -- Ron
Hi Ron.I use AT&T Worldnet as my ISP. They give you 60 Mb of server space to use for e-mail or webpages.
I am probably going to try S-AMe before the end of the week. I'm not sure I want to go above 400mg, though. Hopefully, I'll respond to it similarly to you. We'll see.
I gave low-dosage lithium (300mg) a try, but it worsened my depression. Lithium has always treated me this way, but I had doubted that it would affect me negatively at such a low dosage. I was hoping to have it on-board permanently - if for nothing else, to take advantage of its reported neuroprotective and neurotrophic effects. Of course, it might also have acted as an augmentor of whatever antidepressants I might try in the future. If Manji and others are right, it might make sense for some sufferers of neurodegenerative diseases (bipolar disorder, schizophrenia, Parkinson's, Alzheimer's, Huntington's) to begin taking lithium continuously at dosages between 300-600mg. As is often the case with me, I got screwed once again. Sh_t.
I want to thank you again for your support and encouragement.
- Scott
Posted by petters on May 9, 2002, at 8:57:51
In reply to Re: Nice table Scott » Ron Hill, posted by SLS on May 9, 2002, at 0:30:56
Dear Scott...
Very glad to hear from you again. I have been thinking about you, and your condition. Very sorry for the bad side effect from Litium. I´m sure that you know , that giving it a fair chans taks up to severel month. Do you think there is a chans that the side effect possible wean off after some month? I am quite sure that you also considered that. What about Topamax + Lamictal ( I know you use Lamictal, 300 mg, if my memory is not wrong ) There seems to be many positive result from this combo in treating affective syndrom.
I did follow your advise to raise Lamictal from 100 mg to 200 mg, and it was really positive. More energi, and more stable mood. I also raised my Effexor dosage from 150 mg to 300 mg. 300 mg seems to be an optimal dose for me; I have tried to reduced the dosage to 150 mg severel times but the depression symptom occured. So I must say I´m quite satisfied with my states, except partial sexual dysfunktion. Remeron was the best in this respect in combo with Effexor. But Remeron gave me side effect that I couldn´t tolerated.
So my combo today:
Lamictal 200 mg
Effexor 300 mg
Litium (0.6 mmol/)
Nefadar 400 mgI hesitate to believe that this meds combo will hold, and be sufficient in the future, because I and I know you have experienced so many cruel games with this dam... poop out
Anyway I will think about you and your trial on SA-Me, and pray for your. You have suffer more than enough.
Stay well and be well.
Sincerely
/// Petters
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