# Norepinephrine



## jakeforpresident (Sep 27, 2009)

Norepinephrine seems to be a bad chemical overall. People with SA seem to have higher blood contents of NE as well as people with panic attacks, so it seems all around negative except perhaps as a wake promoting agent.

Does anyone know more about NE than wiki says? If so, is it ever a good thing for SA?

Inderal blocks NE so wouldn't this be an ideal drug for SA? I hear it blocks the formation of painful memories and so could be good for phobias.

Thanks,
-Jake


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## crayzyMed (Nov 2, 2006)

I tried pseudoephedrine before and cant say it made my anxiety worse, it actually improved it, but that can also be caused by the slight increase in dopamine it seems to cause.


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## mark555666 (May 1, 2008)

high adrenaline = animal power 

many professional athletes are pretty much introverted. just watch it.


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## Ehsan (Mar 21, 2009)

NRIs have been shown to have not any effect on SAD. for example atomoxine and imipramine.
however NE has a great role in anxiety and vigilance.
alpha-adrenoceptor agonists are anxylotic.

i think to some meds which block enzymes that convert dopamine to NE.
two goals with one med: dopamine↑ NE↓
i found some but not available for me.
any experience?


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## Ehsan (Mar 21, 2009)

*Neurobiological Mechanisms of Social Anxiety Disorder*


> *Norepinephrine in Social Phobia(October 2001)*
> Since autonomic hyperarousal (manifested by flushing,
> tachycardia, and tremulousness) is a common symptom
> of patients with panic anxiety and social anxiety in performance
> ...


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## Vini Vidi Vici (Jul 4, 2009)

Ehsan said:


> NRIs have been shown to have not any effect on SAD. for example atomoxine and imipramine.
> however NE has a great role in anxiety and vigilance.
> alpha-adrenoceptor agonists are anxylotic.
> 
> ...


yeah i was thinking those would be really sweet, inhibitors of dopamine beta hydroxylase...they might even work great as a single treatment for SA, for a short while at least, before they cause typical psychosis and other dopaminergic effects


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## IllusionalFate (Sep 10, 2008)

*Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin.*



> If increases in NE mediate amphetamine-type subjective effects of stimulants in humans, then one would predict that stimulant medications that produce amphetamine-type subjective effects in humans should share the ability to increase NE. To test this hypothesis, we determined, using in vitro methods, the neurochemical mechanism of action of amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), (1)-methamphetamine, ephedrine, phentermine, and aminorex. As expected, their rank order of potency for DA release was similar to their rank order of potency in published self-administration studies. Interestingly, the results demonstrated that the most potent effect of these stimulants is to release NE. _Importantly, the oral dose of these stimulants, which produce amphetamine-type subjective effects in humans, correlated with the their potency in releasing NE, not DA, and did not decrease plasma prolactin, an effect mediated by DA release. These results suggest that NE may contribute to the amphetamine-type subjective effects of stimulants in humans._





> Medications whose primary mechanism of action is inhibition of NE reuptake (antidepressants) do not produce amphetamine-like subjective effects. Uptake inhibitors activate negative feedback loops which decrease cell firing rates via somatodendritic autoreceptors. This is observed for the dopaminergic, serotonergic, and noradrenergic systems (Diana et al., 1991; Moret and Briley, 1997; Mongeau et al., 1998; Cunningham and Lakoski, 1990). Transporter substrates, however, release neurotransmitter in a nerve-impulse independent manner and are not subject to these negative feedback mechanisms. Since the ability of uptake inhibitors to increase extracellular neurotransmitter is nerve impulse-dependent (Hurd and Ungerstedt, 1989b), reuptake inhibitors may not elevate extracellular neurotransmitter to the level achieved by transporter substrates. This may explain why NE uptake inhibitors do not produce amphetamine-like subjective effects.



Source


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## RockiNToM (Jun 15, 2009)

Speaking from experience of using a NRI called Roboxetine/Edronax it was probably the worst thing a person with an anxiety disorder could ever take. I was climbing the walls with anxiety, and having a panic attacks constantly throughout the day.

However medications such as SNRIs with Serotonin and Norepinephrine isn't such a bad idea because as some of us may know, some anti-depressants can be very sedating. So, having Norepinephrine there can be useful in giving back some stimulation and energy - which is also useful for depression. But as said before, Norepinephrine on its own = bad idea for people with anxiety, speaking from my own experience of course is not to say it wouldn't work out for everyone else as well.

I can't speak for Norepinephrine and Dopamine meds such as NDRIs as I honestly don't know. I can only speculate that people taking those with an anxiety disorder may have the Norepinephrine anxiety provoking effects canceled out by the dopamine effects.


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## Ehsan (Mar 21, 2009)

*one hypothesis about role of 5-HT, NE and CRF in depression and anxiety*


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## db0255 (Jul 20, 2009)

I took an NRI, and other than causing me to feel like my head was "abuzz" it didn't cause me more anxiety. Really rather neutral...so I don't know if you can pin one neurochemical like this as doing over another thing.


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## RockiNToM (Jun 15, 2009)

Well, the one I took, Edronax/Roboxetine has had some pretty bad reviews from many, many people with anxiety nearly everywhere I looked after I decided to come off it. It could just be that Edronax is a terribly made medication or perhaps too potent I don't know. All I know is that medication on its own has only been good for very, very few people.


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## crayzyMed (Nov 2, 2006)

RockiNToM said:


> Well, the one I took, Edronax/Roboxetine has had some pretty bad reviews from many, many people with anxiety nearly everywhere I looked after I decided to come off it. It could just be that Edronax is a terribly made medication or perhaps too potent I don't know. All I know is that medication on its own has only been good for very, very few people.


Reboxetine is just trash.... strattera seems alot better, only works for ADD tough, but it doesnt seem to make ppl feel like **** as reboxetine.


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## jangle1 (Jan 11, 2011)

The reason reboxetine is bad for people with anxiety is because it is a very unique NRI. It targets only the norepinephrine reuptake inhibitor. It does not affect serotonin levels. Therefore it acts only to increase norepinephrine levels.

For me there's something definitely going on with norepinephrine, whenever I go into a social situation I begin to sweat profusely, heart pounding tachycardia, lungs bronchospasm, and I get Raynauds. 

The increased NE explains the lung bronchospasm and Raynauds as well as sweat and heart racing. 

There was a study that said that people with SA have a significantly higher chance of getting NET gene mutations. I have measurably low levels of NET.

I believe there's something going on with norepinephrine in SA.


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## jim_morrison (Aug 17, 2008)

In some studies reboxetine actually seems to help to reduce social impairment and improve social functioning (but not necessarily social anxiety I guess).



> The most recent of these instruments is the Social Adaptation Self-evaluation Scale (SASS), a 21-item scale designed in 1989 to assess patient response to antidepressant treatment. SASS was used in two clinical trials comparing reboxetine, the new selective noradrenaline reuptake inhibitor (selective NRI), with fluoxetine. While no difference in efficacy was detectable by traditional assessments of symptoms, *reboxetine proved to be significantly more effective than fluoxetine in improving social functioning in patients with depression*. *Reboxetine was also more effective than fluoxetine in rectifying social functioning in the subset of patients who remitted from an episode of major depression. Specifically, reboxetine improved patient motivation, energy and self-perception.* These results indicate that antidepressant therapy can achieve more than symptom relief in depression. It is speculated that there may be a difference in the roles played by serotonin and noradrenaline in social functioning.


http://www.ncbi.nlm.nih.gov/pubmed/11226552


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## jangle1 (Jan 11, 2011)

jim_morrison said:


> In some studies reboxetine actually seems to help to reduce social impairment and improve social functioning (but not necessarily social anxiety I guess).
> 
> http://www.ncbi.nlm.nih.gov/pubmed/11226552


Undoubtedly it's more complex than just too much norepinephrine. However I believe that particular effect is in people without prior significant anxiety. For me I'm actually very social when in non performance situations.

So for healthy controls reboxetine only takes them to that zone of increased energy + attention to where they can be more social. However for social anxiety we have way too much norepinephrine in response to social cued anxiety.

Sort of like SSRI, they can be beneficial to some people but in excess they can cause serotonin syndrome. There's definitely a spectrum.

Has anyone tried alpha blockers for their SA? Alpha blockers target the NE receptors.


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## viper1431 (Jun 6, 2012)

Interestingly when i've taken reboxetine i've found it to make me feel really calm and peaceful. It's a lovely feeling.


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## jangle1 (Jan 11, 2011)

viper1431 said:


> Interestingly when i've taken reboxetine i've found it to make me feel really calm and peaceful. It's a lovely feeling.


Essentially what reboxetine does it inhibits your SNS's ability to clear NE. I've gone to a medical center where it was found I had significantly reduced NET. So essentially I'm someone who is having the same effects of reboxetine without ever taking the drug.

I too am really calm and peaceful during non-anxiety provoking situations. However I guess I'm curious - did Reboxetine allow you to give presentations/social performances without anxiety?

something to note when they give SA people yohimbine they find it induces anxiety attacks. Yohimbine is mostly an alpha-2 receptor blocker, which means it sequesters NE to the alpha-1 receptor which is what I believe is the "anxiety" receptor. Alpha-2 stimulation by NE reduces NE output, so by blocking the Alpha-2 receptor with yohimbine they were getting increased NE than otherwise would.

Importantly, when given the same dose to healthy controls, they did not have panic attacks like the SA population did.

I think a viable way to go would be to block the alpha 1 receptor (prazosin) that would sequester NE to the alpha-2 receptor where it will inhibit further NE and thus shut down the panic response.

Prazosin has already shown success in one anxiety disorder PTSD. Haven't seen it tried yet in SA.


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## viper1431 (Jun 6, 2012)

Nah it didn't help with my SA or depression, although i didn't have too much of a chance to try it out. It had the wonderful side effect of feeling like someone was stabbing me in the prostate with a knife.

With regards to prazosin, wouldn't another method be to use clonidine? It's an a2 agonist which then inhibits NE release.


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## jangle1 (Jan 11, 2011)

viper1431 said:


> Nah it didn't help with my SA or depression, although i didn't have too much of a chance to try it out. *It had the wonderful side effect of feeling like someone was stabbing me in the prostate with a knife.*
> 
> With regards to prazosin, wouldn't another method be to use clonidine? It's an a2 agonist which then inhibits NE release.


LOL! Sorry mate.

Well clonidine can help, but it still leaves a1 receptors open for NE to get into.


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## Inshallah (May 11, 2011)

I had a thoracic sympathectomy to eliminate all flushing and sweating on my face and hands and it seems to act as a built-in bèta blocker as well, I'm way more relaxed without the systemic effects of being on a bèta blocker. No sexual hinder for instance.

Might be worth looking into for some of you as well.


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## riptide991 (Feb 1, 2012)

Norepinephrine has the opposite effect on me. When I drink coffee I'm more relaxed. I actually started taking Wellbutrin XL and man this stuff makes me feel so calm and collected. I'm sitting here feeling so relaxed, I've never felt like that before.


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## CD700 (Apr 22, 2010)

I think Norepinephrine is a big issue for people with A typical depression. 
When I first started taking nortriptyline I felt calmer


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