High Dopamine?

[HyperPOTS8]

I just saw Dr Grubb. He now feels there are multiple different phenotypes within the Hyperpots subtype and that this will all be better defined in the coming years.

[Psalm 23]

Kitt. NMPotsie is absolutely right about neurontin. A lot of careful consideration must be given before deciding to take it. It is not a drug to be taken lightly. For many it can cause severe side effects and must be slowly tapered down if you want to discontinue it. I was first prescribed neurontin in 2006 for excruciating shingles pain and it was extremely helpful but after about 3 months I discontinued it as my pain was tolerable. About 6 months later I started to develop chronic fibro like pain in my mid to upper torso and was prescribed lyrica which I took for 18 months but started to develop anxiety and depression symptoms that were totally not me so I realized I had to get off of it and went through 2 weeks of the most horrible withdrawls ever even though it was a slow taper off. After that I started taking the elevil 10mg which helped a lot maybe in part because my pain level had started to reduce.

.

Somewhere around Feb. 2012 I got slammed with severe post herpatic neuralgia in my right arm which radiated across my scapula and clavicle. I have a very high pain threshold but I was in agony so back on the neurontin I went. I thought it would just be temporary but when the post herpatic neuralgia let up, I started developing a problem with burning, stabbing, griping etc, pain in my feet and legs so instead of discontinuing the neurontin I was increasing it. The maximum amount usually prescribed is 3600mg/day. I hate taking any kind of medication but I don't know what else to do at this point. I hope at some point to be able to at least reduce the dose back down but since my what would appear to possibly be SFN pain is only worsening and I am not sure what to do about the sleep issue I am in a bit of a dilemma. I can't say that I have noticed a problem with side effects but I have only been on the 2400mg/day for about 7 month now. I don't know what I would do without neurontin but I would consider it to be a last resort drug

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Thank you for the Methyldopa information. I'm so glad it helps you with sleep. Since clonidine does not help with sleep maybe switching from that to methyldopa would be helpful for me especially if I am able to discontinue the neurontin again. Time will tell.

Elevil is not recommended because it is an anticholinergic drug. After experiencing failure with melatonin I called Mayo back and asked could I just go back to taking elevil and was told no so I never took it again. I would love to go back to taking it but if the neuro feels that strongly about it then I won't.

To everyone else, thank you so much for all the wonderfully insightful, interesting and educational information you have provided. It is so appreciated.

Janet

[ramakentesh]

Norepinephrine is synthesized from dopamine so many people with a very high NE level will also have a high dopamine level--the pathway is rev'ed up. eg in response to hypovolemia or vasodilatation, etc. MIne are also both elevated.

Yes I guess this is true but it is odd that its in serum just floating around.

Norepinephrine shouldn't really be floating around in serum - it should be staying within sympathetic synapses and then being reuptaken into presynaptic vesicles to be reused in the synapse of the sympathetic system. NE is not synthesized in serum, its converted from dopamine precursors neuronally (within the axon and stored within the axon in vesicles). Dopamine can be present in serum but it is very odd to have a neurotransmitter floating around in serum activating random beta receptors.

Increased Norepinephrine synthesis would in theory result in reduced stores of precursors although it doesn't seem to in POTS weirdly. But I don't think its as simple as there just being elevated synthesis of morepinephrine and dopamine because there doesn't seem evidence of this.

Dr Grubb is a fan of the norepinephrine transporter theory which could explain both elevated serum norepinephrine and dopamine. But there may also be receptor super sensitivity, problems with the alpha 2 receptor negative feedback loop that stops too much noreponephrine release and the low flow high anti II crowd which causes release if norepinephrine.

[ramakentesh]

Dr Grubb said in a recent email that he thought hyper should be delineated into NET deficiency, receptor hypersensitivity and beta 1 receptor activating auto antibodies. Although three recent studies suggested Net deficiency dud not result in a hyperagtenergic state so its confusing.

Vanderbilt and Dr Stewart would probably say there are other potential causes as well including hypovolumia/low flow POTS, abnormalities in cerebral auto regulation and compensatory sympathetic activation.

Mayo said they thought the hyperadrenergic state was compensatory or an epiphenonema in their study entitled 'The mayo clinic experience' then changed that more recently to suggest they current believe a 'central hyperadrenergic' phenotype in some hyper patients which they have told one patient on Facebook that is a very hard situation to treat.

[ramakentesh]

Not to mention neuropathy with denervation supersensitivity - with massive NE levels - one of whom on this site responded to SNRIs.

A patient on facebook reports daily NE levels in excess of 5,400! This simply couldnt be NET deficiency without also some sort of upregulation of NE synthesis - its just an incredibly high NE level! Which makes one think of Mayo's idea of a primary central problem where the brain is just telling the body to produce and release too much NE and perhaps dopamine. How you'd treat that I have no idea. But id probably start with considering alpha 2 agonists or SNRIs which could suppress sympathetic outflow via brain stem alpha 2 receptor stimulation.

Hope my ramblings are helfpul - for once im not typing on an annoying phone.

[Carrie]

Thanks for the fascinating info, Rama. What you said about NET deficiency makes sense. The body would likely downregulate further NE production if there was "enough" in the synapse due to NET deficiency. I think there were several cases discovered of NET deficiency leading to high NE, and thereafter anyone with "hyper" symptoms assumed NET deficiency.

I'm currently working through the "Primer on the Autonomic Nervous System" textbook and came across this sentence:

"One must, therefore, keep in mind the indirect and distant relationship between plasma NE levels and sympathetic nerve activity in interpreting plasma NE levels."

For example, my plasma adrenaline came back low, and norepinephrine was in normal range, yet I experience all the "hyper" symptoms.

I'm thinking there will be a group of POTS people whose problems are due to CNS dysregulation rather than just blood vessels in the legs.

[Joann]

Carrie, I have often felt that was the case. One of the things I have wondered is if my system is over-reactive. I am drinking the water and gatorade but honestly i don't think mine has anything to do with blood volume or the vessels in the legs. I did have a volume test and it was pretty close to normal. I am still drinking a lot figure it can't hurt, but I do not salt load, since I am having high blood pressure problems.

[HyperPOTS8]

Rama-- yes, at Mayo they told me "you have a pheochromocytoma without the pheochromocytoma, presumed to be due to brainstem dysregulation." Anything stimulating like driving on the highway or going to my kids' basketball games causes my BP to shoot up, etc. I have antiphospholipid syndrome which the MD who described that syndrome believes is the cause of my autonomic disorder. This syndrome causes various disorders of the CNS, including seizure disorders, movement disorders, etc with the mechanism felt to be due to "sludging" or microthrombosis and/or direct anti neuronal effects of the antiphospholipid antibodies.

[Psalm 23]

So sorry for my last long, inappropriate and not relevant to this topic post. I wish I had something more to contribute in regards to all the thoughts and theories behind hyper pots but I think you have it all pretty well covered. There would appear to be a number of possible root causes and subtypes that continued research will reveal.

[badhbt]

Joann

I think the same thing. All the POTS treatments and medications geared at increasing blood volume have done nothing for me.

[issie]

Hmmm, Rama - I appreciate your "ramblings". I didn't see this thread until after I questioned this on another thread. I want to re-read this and get a better grasp on what you said.

Issie

[ramakentesh]

All interesting posts.

I do well on volume expanding meds but many don't despite the suggestion that most hyper should.

the original proband (patient) with net deficiency reports hypertensive responses to similar stimulus.

What happens to me is that my blood pressure goes up in response to things that should make it go down whereas licorice, florinef and midodrine decrease it and my dizziness.

[ramakentesh]

A doc once suggested that in net deficiency vasoconstrictors would stop the body relying on sympathetic synapses and NE to vasoconstrict, stopping the body from squirting out all the NE because of faulty transporter.

[Psalm 23]

Rama. Thank you so much for all the amazing amount of information shared, I can't imagine how much time you invest in research. I find myself rereading over your posts and trying to understand the meaning of some of them. I would have thought having a nursing background helpful but not the case. I am grateful though because you have challenged my foggy brain to reach for greater heights and for that I am grateful.

Janet

[RichGotsPots]

I have zero Dopamine, or at least it came up to low calculate. And 2 other ppl here told me they had the same. My NE was 634 after 10 min standing, bet it would be at least double or triple if I went 30 min.

[issie]

In the conversion process line of things ---NE comes after/from dopamine. So, me just thinking out loud. Seems that dopamine would probably be high if NE levels are high. Those with low dopamine - probably would not register as high NE with standing. Just me thinking out loud. Don't know for sure. Would be an interesting poll topic --if someone wants to make one.

Issie

[anna]

Can I ask your collective brains a related question?! My children are on Domperidone for gastroparisis, I have just realised that domperidone is a peripheral dopamine antagonist and has been used also as a drug to help with orthostatic hypotension:

TREATMENT OF AUTONOMIC NEUROPATHY

TREATMENT OF ORTHOSTATIC HYPOTENSION (Part One)

Roy Freeman, MD

Associate Professor of Neurology Harvard Medical School Boston, MA USA

Dopamine Antagonists

The dopamine antagonists metoclopramide and domperidone may also treat orthostatic hypotension. These agents most likely inhibit the vasodilating and natriuretic effect of dopamine or increase noradrenalin release due to blockade of prejunctional inhibitorydopaminergic receptors.

Now, as my children do actually seem to benefit OH wise, from taking this med could it be plausible to think that this may have something to do with why my children's dr. can not find any haemodinamic changes when he does their TTT's but they are still very symptomatic.

[Psalm 23]

Anna,

It seems plausible to me. If the domperidone is resulting in reduced vasodilating which would decrease pooling and on top of that you have an increase in volume due to a natriuretic inhibition then I should think that would have effect on a TTT result. I would think something along the lines as having a TTT done while on pots meds that result in vasoconstriction and volume expansion. Just a thought.

Janet

[Psalm 23]

Anna,

I also wanted to say how glad I am to hear that your children have benefited to some degree from taking domperidone but so sorry that they continue to be so very symptomatic.

Issie,

What you are saying makes sense. I wonder how high a standing NE level is required to result in a standing dopamine level to rise above what is considered a normal range. I'm sure there are different variables involved in all of this.

[anna]

Janet, thank you.

[issie]

Anna,

Thinking that may be true. However, I know with myself ---sometimes when my bp and hr are perfectly "normal" ---I still feel POTSie. Not thinking that the bp and hr are all there is to POTS. There is more than that and even if this part isn't "registering" an issue. I think there still is one and it goes deeper then those numbers. If there is an autoimmune issue and an inflammatory issue - that would still be there. Tweaking some things and not correcting the core issue - will be like putting a bandaid on a sore. It's still there, just covered up.

Issie

[anna]

So true Issie numbers do not seem to always well in my families case often correlate with symptoms.

[Psalm 23]

Anna,

You,re welcome. I wasn't sure if I expressed myself very clearly in my last post. I have a serious problem with that. I guess what I was trying to convey was the idea that maybe it could be a situation in which a drug induced haemodynamic stabilization is occuring.

Hopefully others will chime in with their thoughts as well.

My heart goes out to you. I can't begin to imagine all that is involved in having two children with serious health issues.

Janet

[Psalm 23]

Anna,

I'm sorry. I meant to say three children and yourself of course.

[RichGotsPots]

@issie- i have no Dopamine but high NE.

@Anna- if what Freeman hypothesises were true then my BP wouldnt be so wacky.