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The Big and Bangin' Pseudo-Advanced Drug Chemistry, Pharmacology and More Thread, V.2

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natural pain killer saliva

http://en.wikipedia.org/wiki/Opiorphin


this seems quite interesting. anyone ever heard or read about this ? i wonder if there are any developments on this. :\

by any developments i actually mean; Therapeutic application of opiorphin in humans would require modifying the molecule to avoid its rapid degradation in the intestine and its poor penetration of the blood–brain barrier.

any clue you chemist junkies
 
This topic comes up all the time (modifying things to cross BBB that would not cross otherwise).

The consensus is no, it's not something that is going to happen. It can be done with things like polysorbate nanoparticles and direct brain infusions, because otherwise "deactivating" the BBB, or protein metabolism in the gut is a bad plan.

There are literally 100s of peptides active at mu/delta opioid receptors. You can find them in meat, cheese, milk, grains, plants, even humans. But none of them are particularly active when administered exogenously because they are transported out of BBB like loperamide. (viz. nobody uses IV endorphin). In addition the peptides may have activity at sites other than mu-OR that we don;t know yet.

I expect that just like most "biologic" drugs that peptidergic opiods won't really go far. I remember there was a designer peptide that crossed BBB for sale some years back - trials were not exactly what I would call promising as it seemed to me it never produced "typical" effects of an opioid, nor reinforcing behaviour.

Please keep posts like this in the B&B thread
 
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Is there any reason to believe that DXM would share the same negative effects on the urinary tract as ketamine and MXE?
 
Damage to the urinary tract is not something that is "common" with ketamine IMO (probably an incidence of one in five hundred, weighted towards heavy users, * i bet there is a genetic component). I personally think some of people induce nocebo in themselves... & of course ketamine can cause schizophrenoid reactions so that doesn't help.

I have never heard of DXM induced urinary tract damage. Nor have I heard of it with MXE, except again in high doses.
 
Thanks for the reply. :)

I sometimes question whether or not I'm imagining things, but it seems like too great of a coincidence that I happen to notice substantially increased urination frequency in conjunction with weekly / bi-weekly MXE use. Along with a number of other folks on these forums. So now of course I am desperately trying to find a kinder substitute... :\ Tisk... what an alluring high.
 
Diuresis is not neccesarily a sign of damage. Look at caffeine - if you use it infrequently it will increase urine output in some people spectacularly. Nobody worries about caffeine induced bladder damage! On the contrary, urinating a lot means your body is flushing the drug from your system.

Ketamine is documented as being a diuretic, I would expect MXE is too.
 
^ Interesting. Although I still notice the effect now, and it has been weeks since any MXE use.
 
^ I found methoxetamine to be a terrible diuretic,to the point of it being virtually prohibitive. FWIW, Ketamine does a similar thing to me, but in a much gentler fashion. "MXE" ( as much as I hate to type that, but I'm tired of spelling it out ;) ) felt downright nasty in this regard. Ketamine and it's bladder issues really seems to vary, I went through a period years ago of prolonged outrageous consumption and never had any bladder pains or such, just temporarily increased output. Yet some people run into issues much easier. . .who knows.. The jury is still out on this one, (in terms of cause and effect, not the existence of, which is now widely recognized) according to the literature. The norketamine metabolite has been much bandied about bluelight over the years, but this seems to only be conjecture.

Caffeine also isn't the extreme diuretic most assume it is. IIRC it isn't much of one until large amounts are consumed, like >4-500 mg. But the example still works :)
 
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Explain? That is a very simple statement about a complex subject. Sure, they are often prescribed (some types) and can decrease the risk of strokes, high blood pressure, heart attacks, etc. But there is a documented link between diuresis and an increased risk of diabetes, which can also cause the aforementioned HBP and heart attacks, among other things. So how are they healthy in their own right? It's not that simple. . .
 
I thought that misuse of diuretics was also a cause of electrolyte imbalances of all sorts as well.

In the short term diuresis is probably not of concern; but long term diuretic therapy, esp. with "selective" diuretics like furosemide is not going to be healthy for everyone
 
Q about mu opioid agonism, tramadol/tapentadol/NRI opiates, and norepinephrine.

Tramadol and tapentadol are both NRIs(tramadol is an SSRI too but that doesn't matter here), therfore they both increase norepinephrine concentrations in the brain. Well, I remember reading one of the effects of mu-opioid agonism is that it DECREASES norepinephrine and one of the causes of opiate withdrawal is too much norepinephrine. So....shouldn't this make tramadol WDs less intense than other opiates rather than worse like many people say? And shouldn't taking tramadol when withdrawing make the WDs worse due to it increasing NE? Or am I totally off base here?

And another semi-related question. Since tramadol is a serotonin releasing agent(yes, it's a releasing agent, not JUST a reuptake inhibitor) as well, and mu-opioid agonism also increases dopamine, how come tramadol isn't empathogenic(or is it? I've never had it so I can't say.) like MDMA, which also releases serotonin and dopamine?
 
Given that norepinephrine antagonists (anti-adrenergics like clonidine) are used for w/d from opioids, I see where you're coming from. But I would be more inclined to think of Tramadol as a SNRI plus opioid. Do you think SNRI withdrawal, plus opioid withdrawal, would cancel each other out?

Remember, "drug X increases monoamine Y" is pretty meaningless. Where does the increase happen, and under what circumstances?
 
sekio said:
Given that norepinephrine antagonists (anti-adrenergics like clonidine) are used for w/d from opioids, I see where you're coming from. But I would be more inclined to think of Tramadol as a SNRI plus opioid. Do you think SNRI withdrawal, plus opioid withdrawal, would cancel each other out?

Remember, "drug X increases monoamine Y" is pretty meaningless. Where does the increase happen, and under what circumstances?
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Well as for the 2nd part of my post, since both MDMA and tramadol are considered "serotonin releasing agents" I'd assume they both released it in the same way albiet at different intensities.
 
They're not very structurally related. I can pretty much guarantee they release in different regions. Sekio is trying to tell you that just because two drugs both release a neurotransmitter, doesn't mean the effects will be the same.
 
SSRI damage - is there anything?
I wonder why so many people dislike SSRI and blame it for having bad impact on your health?
Is it true, especially i wnat to know about fluoxetine. Can it ruin your serotonin or other neruomediators metabolism permanently?
 
Well as for the 2nd part of my post, since both MDMA and tramadol are considered "serotonin releasing agents" I'd assume they both released it in the same way albiet at different intensities.
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Not only would expect the compounds to be differently selective for anatomical region, but tramadol's mechanism of transporter reversal might simply be a bit different, given that a prior study found its efficacy as a releaser to be subject to clear 'ceiling effects'.

ebola
 
I don't think SSRIs are that bad. Many people are upset that they offer little/no recreational potential.
Its definitely possible. How long or at what intensity of usage this happens is hard to say
 
Ho-Chi-Minh said:
I don't think SSRIs are that bad. Many people are upset that they offer little/no recreational potential.
Its definitely possible. How long or at what intensity of usage this happens is hard to say
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A lot of people are resentful or afraid of them due to the sexual side effects that can be extreme and last a long time in some.
 
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