Tramadols way of releasing 5-ht- is it unique?

[T9358]

compared to say MDAI or the MDxx's and even the APB's, does tramadol release 5-ht a different way? Why does it feel so different than the other SRA's, I know it

has complex pharmacology ex: NMDA antagonism/5-ht2c antagonism/norepinephrine re-uptake inhibition ect ect. But why does it feel so different?

If there could be a final in depth look at this it would be so helpful and useful ( my psych is rxing this off label for treatment resistant depression) and is having incredible results.

****Sekio you have always been a great help to me could you or any of your insanely smart crew help me, I know tram is looked by most at BL as trash but for some depressed folk its the top of the line compared to the current batch of crap ive had to cycle through for years.!!

 

[Hammilton]

It doesn't seem to have been determined yet, so.... maybe?

 

[sekio]

I think it's a plain old SSRI like any other, it feels different because it's a multi-action drug that also has opioid agonist & NE reuptake inhibition effects.

Most serotonin releasers aren't opioids... MDMA and APB sure aren't The lucky percentage of the population that metabolises more tramadol to desmethyltramadol will also get a much stronger opioid effect.

Have you ever had tapentadol? That could be interesting.

 

[ebola?]

No, one study suggested that it has some sort of releasing effect as well, though not at levels of efficacy anywhere near entactogenic 5ht releasers. Unfortunately, the study used rather indirect indicators to confirm releasing activity, so it wasn't much more specific than that, and it might occur in vitro but not appreciably in vivo.

ebola

 

[Toz]

One thing going for tramadol being a NMDA antagonist is that it can get people (including me) high while using buprenophine. It still retains it's warmth, but it's not the usual opioid warmth, it's more in line with the effects of phencyclidine or methoxetamine. Based on that, I will speculate that it works as an nmda antagonist.

 

[endotropic]

No, one study suggested that it has some sort of releasing effect as well, though not at levels of efficacy anywhere near entactogenic 5ht releasers. Unfortunately, the study used rather indirect indicators to confirm releasing activity, so it wasn't much more specific than that, and it might occur in vitro but not appreciably in vivo.

I know I've read this one, but if you know where to find it I would really appreciate a link.

One thing going for tramadol being a serotonin releaser is that it can get people (including me) high while using buprenophine. It still retains it's warmth, but it's not the usual opioid warmth, it's more in line with the effects of phencyclidine or methoxetamine. Based on that, I will speculate that it works as a serotonin releaser.

Based on that evidence wouldn't it be more rational to conclude that tramadol is acting as an NMDA antagonist?

 

[ebola?]

I know I've read this one, but if you know where to find it I would really appreciate a link.

I was about to ask that, heh. I had trouble finding it earlier.

Based on that evidence wouldn't it be more rational to conclude that tramadol is acting as an NMDA antagonist?

Exactly: "active despite blockade of mu receptors" is not firm enough evidence to establish it as a likely 5ht releaser. In terms of subjective experience, you'd expect some effects similar to MDAI or similar compounds (but this is really weak corroborating evidence).

ebola

 

[Toz]

I know I've read this one, but if you know where to find it I would really appreciate a link.




Based on that evidence wouldn't it be more rational to conclude that tramadol is acting as an NMDA antagonist?

Yes, that was what I meant, no idea why I wrote serotonin releaser instead, I was probably high. This is probably the effect that nets tramadol it's special warmth and neuropathic pain relief.

Doesn't tramadol work as an SNRI? It's chemical structure closely resembles venlafaxine.

I was about to ask that, heh. I had trouble finding it earlier.

Do you mean this study? http://bja.oxfordjournals.org/content/79/3/352.full.pdf+html

 

[AlphaMethylPhenyl]

^Yeah. Seems like if its a releaser and reuptake inhibitor of 5-HT it could lead to serotonin syndrome. Don't know if a seizure would precede this though. The paper sounds like its saying that 5-HT release itself has significant painkilling effects. Anything else on this? Confirmation?

 

[endotropic]

^Yeah. Seems like if its a releaser and reuptake inhibitor of 5-HT it could lead to serotonin syndrome. Don't know if a seizure would precede this though. The paper sounds like its saying that 5-HT release itself has significant painkilling effects. Anything else on this? Confirmation?

SSRI antidepressants are first line treatment for painful peripheral neuropathy:

Treatment of painful peripheral neuropathy.

Neuropathic pain management is an important aspect in the management of painful peripheral neuropathy. Anticonvulsants and antidepressants have been studied extensively and are often used as first-line agents in the management of neuropathic pain. In this article, data from multiple randomized controlled studies on painful peripheral neuropathies are summarized to guide physicians in treating neuropathic pain. Treatment is a challenge given the diverse mechanisms of pain and variable responses in individuals. However, most patients derive pain relief from a well-chosen monotherapy or well-designed polypharmacy that combines agents with different mechanisms of action.

 

[ebola?]

Do you mean this study? http://bja.oxfordjournals.org/content/79/3/352.full.pdf+html

That's it, thanks.
Okay, so from a preliminary reading, it seems that tramadol was demonstrated to increase synaptic 5ht in a way decoupled from its efficacy in blocking its reuptake. However, the study fails to make a direct measure confirming the mechanism involved. The study also suggests that endogenous release is enhanced, rather than what we see with entactogens, where 5ht release occurs regardless of cellular signalling. So with tramadol, we'd expect a comparatively greater increase in phasic serotonergic activity, where traditional entactogens induce comparatively more increased tonic activity.

ebola