Theoretical Novel Dissociative: CNS 5161

[Nervewing]

Hello,
If any of you are around reddit you may have seen me post about this already but I'll drop it here too
Just in the interest of exploring novel compounds, I was poking around the literature for a bit to find NDMA antagonists and then survey them for their potential psychoactive effects.

Enter CNS 5161:

CNS 5161 is a novel drug currently in the clinical trial stage for the treatment of neuropathic pain, something which other popular dissociatives have been analyzed for. It's feasibility seems to be hindered due to the reported side effects, which include dysaesthesia, numbness, lightheadedness, derealization, drowsiness, dizziness and visual disturbances. A pretty familiar array of effects, correct? The drug was administered at pretty low doses however, and all of these effects were described as mild.

So this leaves me curious as to what a dose beyond the therapeutic range may yield. Could full on dissociative effects be expected? Could they just manifest as "mild" like described in the paper and only the negative somatic effects increase with dose? Idk, I don't know much about pharmacology so its hard to say. Perhaps the folks here will have something to contribute.
The most worrisome side effect described is "Prominent cardiovascular effects were seen at doses of 1 mg and above. A 15–20% increase in mean arterial pressure was apparent", which I was informed is a pretty substantial and dangerous increase in blood pressure. Does this entirely preclude it's potential as a dissociative?

sources:
http://onlinelibrary.wiley.com/doi/10.1002/jlcr.1033/abstract
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1874317/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2000615/

my full write up on it (though I really put all the important information here):
http://nervewing.blogspot.com/2016/04/new-frontiers-cns-5161.html

 

[Solipsis]

On the one hand the reported side-effects don't necessarily mean anything, but on the other hand there are vague similarities to known NMDA antagonists.

A lot of NMDA antagonists do seem to have potential as vascular enhancers including of the brain, but I guess there are limits to what is helpful and not downright dangerous. But I do not know if this would actually make it unsafe.

Hopefully it might seem like a lot of data to go on, but skeptically it seems like way to little data...

 

[WSH]

I've looked it up and it says it's a "blocker of the NMDA ion channel", which is a good thing.

I interprete that to mean that it isn't one of those glycine-site-shits (like GLYX-13).

 

[Solipsis]

No, this binds to the PCP site alright. This seems more like material for the NSP forum if you don't mind.

 

[Nervewing]

Should I repost it there or will it be moved?

 

[Xorkoth]

I'll move it.

PD - > NSP. I hope worthy, educated speculation ensures and tickles us all pink (which is a weird saying. Or is it really a saying? I think so. Anyway I digress...

 

[d1nach]

Looks funny to me

 

[Solipsis]

Looks to me like it will be disgusting, a double thioanisole?... It will be a relief not to be a liquid like thioanisole regarding vapor pressure, but thioanisole can completely disgust the shit out of you, haunting you for a day and messing with your appetite and sense of hygiene. Let alone if you would have to ingest it and have it circulate your body... you would be lucky to get your mind so wiped that you have no idea what's going on...

Why don't you switch to the double methoxied analogue and see what's up with that? Might actually have a remotely pleasant smell then, like aniracetam with its anise (well anisoyl there not anisole). Though I do not know if the smell of aniracetam is from unreacted precursor.

 

[sekio]

Looks like an analog of aptiganel, which is a dissociative that apparently works at the Mg site on the NMDAr.

I'm still waiting for someone to make etoxadrol for me. (CL-1848C) They discontinued it because it gave some people hallucinations/nightmares. That bodes well for a fun dissociative though.

 

[WSH]

CAVEAT: this compound could potentially have some MAJOR sigma 1/2 effects (sigma is difficult to separate from the mk-801's NMDA site)

 

[clubcard]

When you know the size & shape of the NMDA receptors, you can see that this must bind in a different manner. The thiomethoxy group opposite a halogen look right but it looks a little too bulky. Don't forget, without at least some dopamine activity, pure NMDA activity isn't so good. Look at diphenidine.

 

[Nervewing]

I for one love diphenidine.... To each their own I guess, every drug has someone who enjoys it, even the deliriants

CAVEAT: this compound could potentially have some MAJOR sigma 1/2 effects (sigma is difficult to separate from the mk-801's NMDA site)

likewise, it's good to know this would appeal to me at least I used to love to DXM combined with CYP2D6 inhibitors (mostly bupropion), do you think this would be similar in nature?

It doesn't seem like the mass appeal for this drug would be very high nevertheless...

 

[sekio]

Diphenidine is Good Shit^tm, I don't think direct DA activity is always needed...

 

[Solipsis]

Seems strange though that something like aptiganel acts at the Mg site but can produce delirium / hallucinations etc... The drug selfotel - cool name and matching structure - is considered to act on the glutamate site but apparently not so selectively that higher doses won't produce PCP-like effects.

So maybe aptiganel isn't so selective either?

And that acetal looks interesting, maybe a way to get some novel shorter acting dissos?

 

[Sturnam]

I'm still waiting for someone to make etoxadrol for me. (CL-1848C) They discontinued it because it gave some people hallucinations/nightmares. That bodes well for a fun dissociative though.

I was able to sample some dexoxadrol and levoxadrol some years back. Dexoxadrol seemed to be a fun, if mild, compound to play with. Admittedly I never dosed too high as I had overdone it with some disassociatives by then. I wrote up a trip report that is on the "dark" version of BL under a similar handle.

I wish I still had the levoxadrol though. I would be curious to combine it with other compounds and see what happens.

 

[sekio]

Everything I've read about would suggest that it's a good contender for the Next Big Dissociative after the O-PCE and friends go in the ban bucket. I keep coming back to this - it was discontinued because of the unusual incidence of trippy dreams after anesthesia... no major side effects otherwise... fast onset/offset when IV... everything about that sounds good to me.

The synthesis seems a bit of a monkeyfuck, but so is any arylcyclohexylamine stuff...

 

[DotChem]

for sure it would cost a bundle as the prep doesnt seem straight! at least for the optically pure with 3 chiral centers!!.. better get a market ready!! ^^ did you iv-it or plugged it? hard to see the dioxolane resisting stomach acids??