# Clonazepam and Serotonergic activity



## JohnG (Sep 3, 2010)

Wiki say: In addition clonazepam decreases the utilization of 5-HT (serotonin) by neurons

How that can be useful for anxiety and SA ? :sus

For what I know clonazepam increase serotonergic activity, that's why is used for SA.http://en.wikipedia.org/wiki/Clonazepam#cite_note-81
http://en.wikipedia.org/wiki/Clonazepam#cite_note-81


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## crayzyMed (Nov 2, 2006)

No, benzo's work because they make the GABAA receptors more sensitive to GABA, this is completely unrelated to serotonine or other monoamines.


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## Medline (Sep 23, 2008)

JohnG said:


> For what I know clonazepam increase serotonergic activity, that's why is used for SA.


Clonazepam is a benzo, it's primary anxiolytic activity comes mainly from it's action on GABA. I think you mixed that up with SSRIs.

Edit: crayzyMed was faster at answering.


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## JohnG (Sep 3, 2010)

Medline said:


> Clonazepam is a benzo, it's primary anxiolytic activity comes mainly from it's action on GABA. I think you mixed that up with SSRIs.
> 
> Edit: crayzyMed was faster at answering.


 *Abstract*

Chronic administration of the benzodiazepine, clonazepam, increased the number of [3H]-hydroxytryptamine (5-HT1) binding sites in the frontal cortex of the rat. The increase reflected a change in the maximum density of binding sites (_B_max) with no change in ligand affinity (Kd). Increased binding occurred after continued exposure (10 days) to large (5.0 mg/kg) doses of clonazepam. The changes in [3H]5-HT binding were regional in that they occurred in membranes from the frontal cortex but not the brainstem. The effects were also at least partially selective for 5-HT receptors since the binding of the β-adrenergic radioligand, [3H]dihydroalprenolol, was not affected by clonazepam. A second benzodiazepine, diazepam, did not affect the binding of [3H]5-HT at doses of 30 mg/kg per day. The latter data suggest that the effects of benzodiazepines on serotonin 5-HT1 receptors are unique to clonazepam.

http://www.ncbi.nlm.nih.gov/pubmed/2418653


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## crayzyMed (Nov 2, 2006)

JohnG said:


> *Abstract*
> 
> Chronic administration of the benzodiazepine, clonazepam, increased the number of [3H]-hydroxytryptamine (5-HT1) binding sites in the frontal cortex of the rat. The increase reflected a change in the maximum density of binding sites (_B_max) with no change in ligand affinity (Kd). Increased binding occurred after continued exposure (10 days) to large (5.0 mg/kg) doses of clonazepam. The changes in [3H]5-HT binding were regional in that they occurred in membranes from the frontal cortex but not the brainstem. The effects were also at least partially selective for 5-HT receptors since the binding of the β-adrenergic radioligand, [3H]dihydroalprenolol, was not affected by clonazepam. A second benzodiazepine, diazepam, did not affect the binding of [3H]5-HT at doses of 30 mg/kg per day. The latter data suggest that the effects of benzodiazepines on serotonin 5-HT1 receptors are unique to clonazepam.
> 
> http://www.ncbi.nlm.nih.gov/pubmed/2418653


Interesting, but thats still a "side effect" of clonazepam rather then its main action, wich its gaba related. This probably has little relevance to its therapeutic effects.


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## JohnG (Sep 3, 2010)

Of course! Was just to inform people who use it of a little serotonin activity of clonazepam, that can help SA, in some manner. :yes


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## bben (Oct 24, 2009)

clonazepam is the ONLY benzo that works well for HPPD and it is used because of its unique effect on serotonin utilization by the neurons. It is also used for depersonalization disorder and is first line because of its unique serotonin affects. 

It is a very important part of clonazepam and should not be written off or marginalized, it is a very unique benzo. I have been aware of this effect sometime now and have a knowledge of it since i took it for DP/DR for 1 year and it is the only benzo that did anything for me.


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## JohnG (Sep 3, 2010)

bben said:


> clonazepam is the ONLY benzo that works well for HPPD and it is used because of its unique effect on serotonin utilization by the neurons. It is also used for depersonalization disorder and is first line because of its unique serotonin affects.
> 
> It is a very important part of clonazepam and should not be written off or marginalized, it is a very unique benzo. I have been aware of this effect sometime now and have a knowledge of it since i took it for DP/DR for 1 year and it is the only benzo that did anything for me.


So clonazepam effects the binding of serotonin to his receptors. After an 1 year of use, do you have some tolerance problem I bet ?


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## Canadian4Life (Sep 27, 2010)

The effect clonazepam has on serotonin is actually a very important part of the drugs mechanism of action. That's the reason why it also possesses potent anti-manic effects which other benzos have not been shown to have.


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## crayzyMed (Nov 2, 2006)

Canadian4Life said:


> The effect clonazepam has on serotonin is actually a very important part of the drugs mechanism of action. That's the reason why it also possesses potent anti-manic effects which other benzos have not been shown to have.


Interesting, i wasnt aware of the unusual property's of this one!


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## Canadian4Life (Sep 27, 2010)

crayzyMed said:


> Interesting, i wasnt aware of the unusual property's of this one!


That's why no other benzo worked for me. Valium but lost effectiveness quick. Clonazepams effect on serotonin is a major part of how clonazepam helps anxiety with me. The gaba effects go away but only clonazepams true anxiety reducing effects dont go away. I think the reason some people don't get tolerant to clonazepam is because they seek the effect it has on serotonin and tolerance doesn't build to this specific effect.


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## medjuggler (Jan 26, 2011)

*Oh deary me! Kindergarten lesson #1*

*HI!* 
*
I must start by saying that I'm certainly no doc, but I'm more than a little shocked at the amount of confusions & disinformation going on in this thread. Does anybody here actually search the web and NOT simply let Wikipedia be there guide? The site has its uses & SOME very usefull facts, but I mean...OK, sarcasm over :teeth

I've been on clonazepam for over 5yrs now. My SA was bad, most probably AvPD. Phenelzine worked wonders, till it pooped out despite countless efforts to augment.

When I came off phenelzine I'd been on 1.5mg clonazepam for 6 months. Next AD med I eventually found helpfull was isocarboxazid (Marplan), another MAOI. Im still on it. Fantastic AD but did nothing for my SA. So, once i hit 80mg of iso. my pdoc doubled my clonazepam to 3mg, whilst also allowing up to 4mg if needed.

I plodded along, getting used to the heaviness of 3mg, which soon dissappeared, but although the dose increase helped alot more, it wasn't consistant and never lasted for as long as I needed it to :no So f**k it, I went to 4mg/day. 1.5mg morn, 1.5mg midday & 1mg at night. 
The result? Social anxiety 80% gone from within a week at 4mg to present day  NO DOSE INCREASE HAS EVER BEEN NEEDED SINCE!

I've learned some very essential rules for taking clonazepam the best way, and for maximum efficiacy:

1. Find the right dose for you. That means increase slowly untill it helps you- aim for at least 70% less anxiety.

2. NEVER miss a dose- you will FEEL the difference within a day if you do.

3. Spread your daily dose best you can. I take 3 doses, so thats every 8hrs or as close to that as possible.

4.NEVER take more than the dose that works. It will provide no extra benifit, make your brain foggy and most probably mess with your mood balance for a short while, which of course just aint fun. And dont get tempted by the thought of euphoria coz you wont get any-I 'know'.

Think this is all totally not the way at all? Then let me also add that I am a drug addict and an alcoholic, just got sober (again) 16 days ago. Still dabble with the odd psycho-stim on rare occasions (ie, going clubbing all night, etc) but nothing else. 
And have I EVER found clonazepam to be addictive or even more-ish? :no Not at all! And nobody I have let try them (mainly as a sleep aid) thinks so iether. In fact its the least addictive benzo on the market and thats most probably because its THE most anti-euphoric benzo. Only heroin addicts use it to get 'higher' as it increases the effects of heroin and methodone.

Mind you, I must admit that its also one of the more 'depressing' benzos, so an AD of choice is sometimes needed too. Just a light dose if you dont already have depression.

Oh yeah :idea the 5-HT effect! 
It does decrease serotonin activity, but the receptor it effects is known to be excitory and so antagonising this activity means calming the mind even more so than just the usual GABA-a agonism. Hence why it may be given during the 1st 2 weeks of SSRI treatment, to help avoid that common start-up anxiety thats so common with all SSRIs. 
Also I've no doubt that this antagonism is why even non-depressive patients may need some AD help whilst taking clonazepam.

I just wanna add too, that if you think this is just personal experience ONLY or that I'm an odd-one-out :roll then you are mistaken. Ive learned how to best take this med not only from my doc or my own interventions, but largely from other clonazepam users too, from the help they've given with all thier facts, suggestions, ideas & support. Where are these people I found? 
www.dr-bob.org/babble
Just take a peak. Its full of info you wont find anywhere else without some difficulty! Not to everyone's taste, but each to thier own!

But dont get me wrong! Im a new member here and look forward to learning, sharing and perhapse even i little fun too :boogie

Soz for the long post!
Over & out.
Med*


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## martyboi (Sep 18, 2009)

JohnG said:


> *Abstract*
> 
> Chronic administration of the benzodiazepine, clonazepam, increased the number of [3H]-hydroxytryptamine (5-HT1) binding sites in the frontal cortex of the rat. The increase reflected a change in the maximum density of binding sites (_B_max) with no change in ligand affinity (Kd). Increased binding occurred after continued exposure (10 days) to large (5.0 mg/kg) doses of clonazepam. The changes in [3H]5-HT binding were regional in that they occurred in membranes from the frontal cortex but not the brainstem. The effects were also at least partially selective for 5-HT receptors since the binding of the β-adrenergic radioligand, [3H]dihydroalprenolol, was not affected by clonazepam. A second benzodiazepine, diazepam, did not affect the binding of [3H]5-HT at doses of 30 mg/kg per day. The latter data suggest that the effects of benzodiazepines on serotonin 5-HT1 receptors are unique to clonazepam.
> 
> http://www.ncbi.nlm.nih.gov/pubmed/2418653


This study doesn't show anything relevant to humans taking clonazepam at therapeutic dosages. It looks like the doses they gave these rats were massive (5mg/kg)... thats ridiculous. even for a human, thatd be enough clonazepam to kill a person within a few minutes


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## JohnG (Sep 3, 2010)

martyboi said:


> This study doesn't show anything relevant to humans taking clonazepam at therapeutic dosages. It looks like the doses they gave these rats were massive (5mg/kg)... thats ridiculous. even for a human, thatd be enough clonazepam to kill a person within a few minutes


That is a very precious and scientific contribute, thanks ! :no


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## metamorphosis (Dec 18, 2008)

Benzos=GABAa
You'd rather see me in the pen, than me and Lorenzo rolling in a Benzo!!


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## Charles Ferdinand (May 4, 2012)

Sorry to bump, but for future reference, I just had to clarify that Clonazepam DOES decrease the level of Serotonin in the brain. And, no, despite what any other person says, it's no freaking side-effect, Clonazepam does this DIRECTLY, and even if it was a side-effect (and, again, IT IS NOT), what difference would that make? 
It basically increases the levels of Serotonin Transporter (SERT) in the serotoninergic neurons, thus increasing the Serotonin Re-Uptake, essentially doing the opposite of what SSRIs do. 

Regards! 
Dr. Ferdinand.


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## Caedmon (Dec 14, 2003)

Charles Ferdinand said:


> It basically increases the levels of Serotonin Transporter (SERT) in the serotoninergic neurons, thus increasing the Serotonin Re-Uptake, essentially doing the opposite of what SSRIs do.


Thank you for an explanation in plain English, my brain is not processing today.  That's interesting. I find clonazepam to be depressiogenic if i take it continuously longer than about a week or two. Have had this happen several times over the years. A serotonin interaction would be compatible with this effect.


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## wealldead (Jun 20, 2014)

medjuggler said:


> *HI!*
> *
> I must start by saying that I'm certainly no doc, but I'm more than a little shocked at the amount of confusions & disinformation going on in this thread. Does anybody here actually search the web and NOT simply let Wikipedia be there guide? The site has its uses & SOME very usefull facts, but I mean...OK, sarcasm over :teeth
> 
> ...


Hello, how long are you at the same time on clonazepam and Marplan?

And how long your anxiety you alot it down?

thank you


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## Mustafa (Aug 15, 2012)

I don't think he's gonna reply mate.


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