Na+ ch. blocker that's also a DAT substr. Anyone?

[Nagelfar]

It's been a while, anyone miss me? Did a stint in Walla Walla. Don't ask.

Thinking of DAT substrates (not uptake inhibitors) that are sodium channel blockers. Any ideas or actual instances for me?

Also, I recently had a genetics test done, I don't have all the info with me, but apparently I am a non-standard polymorphism for the 2a serotonin receptor. Any indication of how this would effect medications or just my own neurobiology? (P. S. psychedelics have never worked on me, though I've not done large amounts by far, salvinorin either)

 

[polymath]

Hi, I remember you.

Isn't the local anesthetic effect of cocaine caused by sodium channel blockage? Receptor polymorphisms can cause ligands to bind to them with greater or smaller affinity, or cause a different kind of intracellular response. Some 5-HT2A polymorphs seem to have something to do with self-destructive behavior.

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects - Neuropsychopharmacology

Serotonin 5-HT2A receptor (5-HT2A) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive–impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive–impulsive traits has not been established. This study examines...

www.nature.com

The CC genotype in HTR2A T102C polymorphism is associated with behavioral impulsivity in alcohol-dependent patients

High levels of impulsivity can increase the vulnerability for development of alcohol dependence. Moreover, impulsivity is considered to be a predictor of poor treatment outcomes. Few studies, however, have directly examined the genetics of impulsivity ...

www.ncbi.nlm.nih.gov

Some 5-HT2A polymorphs are related to having visual disturbances during migraine headache attacks

Association of the T102C polymorphism of 5-HT2A receptor gene with aura in migraine - PubMed

The T102C polymorphism of the 5-HT2A receptor gene is not directly related to the increased risk of migraine. The associations between the genotypes of this gene and aura may suggest that 5-HT2A receptor gene polymorphism may be involved in determining the subtypes of or accompanying symptoms in...

www.ncbi.nlm.nih.gov

 

[Nagelfar]

Cocaine does indeed but it is an uptake inhibitor not a substrate, which is why I am asking an example, I started the cocaine analog page, I should know there. ; -)

I am not CC but GG

Here is Assurex Genesight overview that was paid for by my insurance:

Pharmacokinetic genes:
HTR2A has a G/G SNP, supposedly increasing the sensitivity
HLA-A shows A/A, and 3101 allele
HLA-B with 1502 allele is not expressed, lower risk of side effects from SSRI medications

Pharmacodynamic genes:
CYP2D6 has 4 & 41, making me a poor metabolizer of that enzyme, keeping it in vivo longer
CYP2C9 1 & 2
&
CYP3A4 1 & 22 are intermediate in activity
UGT2B15 shows reduced activity on one expressed of the pair but says normal extensive metabolizer

It also gives unique genes I have that the Assurex company has not come across before, in that same area, I will have to pull those next time.

 

[polymath]

For some reason I read it wrong even though you explicitly said substrates not reuptake inhibitors. The Merck Index says about the taste of amphetamine: "bitter taste, followed by numbing sensation". Maybe this means that it can also block sodium channels to some extent, or then there are many ways how an amine can act as a local anesthetic.

The G/G version of 5-HT2A gene has something to do with OCD:

Serotonin Related Genes Affect Antidepressant Treatment in Obsessive–Compulsive Disorder | Progress in Neurotherapeutics and Neuropsychopharmacology | Cambridge Core

Serotonin Related Genes Affect Antidepressant Treatment in Obsessive–Compulsive Disorder - Volume 3 Issue 1

www.cambridge.org

Edit: The tricyclic antidepressant imipramine is a blocker of voltage gated sodium channels. I think this makes it likely that the amineptine-like tricyclics, which also happen to be DA releasers, block Na channels as a side effect (even though I can't find a reference verifying this).

Inhibition of Na(+) current by imipramine and related compounds: different binding kinetics as an inactivation stabilizer and as an open channel blocker - PubMed

Use-dependent block of Na(+) channels plays an important role in the action of many medications, including the anticonvulsants phenytoin, carbamazepine, and lamotrigine. These anticonvulsants all slowly yet selectively bind to a common receptor site in inactivated but not resting Na(+) channels...

www.ncbi.nlm.nih.gov

 

[AlphaMethylPhenyl]

Wouldn't make much sense, as far as I know. Dopamine is a catecholamine, so blocking Na+ would reduce neural activity, but I guess it depends on what type of neuron it selects for the overall effect. I guess on a GABA (like some terpenes) or adenosine neuron (like caffeine) it would work. But it's kind of moot, as we have a stimulant that's not hard on the brain and is relatively simple in action: methylphenidate.

What you're talking about is reducing neural activity. As far as I know, doing it like that could cause some gnarly necrosis. But, I defer to more knowledgeable minds on that.

 

[Nagelfar]

For some reason I read it wrong even though you explicitly said substrates not reuptake inhibitors. The Merck Index says about the taste of amphetamine: "bitter taste, followed by numbing sensation". Maybe this means that it can also block sodium channels to some extent, or then there are many ways how an amine can act as a local anesthetic.

The G/G version of 5-HT2A gene has something to do with OCD:

Serotonin Related Genes Affect Antidepressant Treatment in Obsessive–Compulsive Disorder | Progress in Neurotherapeutics and Neuropsychopharmacology | Cambridge Core

Serotonin Related Genes Affect Antidepressant Treatment in Obsessive–Compulsive Disorder - Volume 3 Issue 1

www.cambridge.org

That would make sense for me, certainly.

As for Na+ blockage questions, I have some theories regarding electron clouds, complete, hobbyist drivel most likely. At the library currently, only have so much time online.

As for getting my results posted here:

To: ARX_medinfo <[email protected]>
Subject: I have done your service through Corehealth in Longview, WA

I am wondering how I can see my results online. I have a printed copy, but I'd like to share it with certain parties and hobbyists online.

Sincerely

And I get this:

Customer Support <[email protected]>

If you're looking to obtain results that were ordered out of a different providers office then you may submit a 'release of information form' (see attached). Documents may be returned via email or by fax to 888-894-4344.

Please feel free to reach out to customer support at 866-757-9204. We are available 8am-8pm EST Monday-Friday.

Ashton Limpert
Patient Advocate | Myriad Neuroscience
6960 Cintas Blvd, Mason, Ohio 45040
Office: 866.757.9204 | Fax: 888.894.4344
[email protected]| www.myriad.com
http://www.myriad.com/
This message and any attached documents contain information from Myriad Genetics, Inc. that may be confidential and/or proprietary. If you are not the intended recipient, you may not read, copy, distribute or use this information. If you received this transmission in error, please notify the sender immediately by reply e-mail and then delete this e-mail

What a pain.

 

[Nagelfar]

Is there a way to upload .pdfs?

 

[sekio]

There should be a way to attach files but I don't see it, but could you put it on Google Drive maybe?

Also, your local library may offer free use of a document scanner if you ask 'em.

 

[S.J.B.]

There should be a way to attach files but I don't see it, but could you put it on Google Drive maybe?

Attachments were just disabled across the forum.

 

[Nagelfar]

Wouldn't make much sense, as far as I know. Dopamine is a catecholamine, so blocking Na+ would reduce neural activity, but I guess it depends on what type of neuron it selects for the overall effect. I guess on a GABA (like some terpenes) or adenosine neuron (like caffeine) it would work. But it's kind of moot, as we have a stimulant that's not hard on the brain and is relatively simple in action: methylphenidate.

What you're talking about is reducing neural activity. As far as I know, doing it like that could cause some gnarly necrosis. But, I defer to more knowledgeable minds on that.

There is DAT specific sodium channels and several conformations of DAT, greater overall affinity in assay may be result, but once phosphorylated such affinity might have novel unforeseen open or closed to out strictures on DAT. Have you read about the SoRI-20041 and other number compound that, with amphetamine, has a variant that augments release from DAT in either direction (greater or lesser, separate compounds but near identical) or the cocaine-like tropanyl spirocyclic isoxazoline compounds that flick DAT from off and unreceptive to on and allowing uptake?

The potential of the latter as a potentiator shouldn't get overlooked, since upregulation includes foremost DAT turning off, to nonacceptive, position, those tropanyls would just force them to on, bypassing a large portion of immed. cause of tolerance. There is also one for SERT (infact the study focuses on that one and glosses over the one that targets DAT and does the same).

It is so much more than just the outcome of a dopamine releaser with a local anesthetic, as your answer seems to paint it as.