Psychoactive signalling modulators

[Jonneh]

I came across the following fascinating passage from this wiki quoted in a thread here:

One notable example of functional selectivity occurs with the 5-HT2A receptor, as well as the 5-HT2C receptor. Serotonin, the main endogenous ligand of 5-HT receptors, is a functionally selective agonist at this receptor, activating phospholipase C (which leads to inositol triphosphate accumulation), but does not activate phospholipase A2, which would result in arachidonic acid signalling. However, the other endogenous compound Dimethyltryptamine activates arachidonic acid signalling at the 5-HT2A receptor, as do many exogenous hallucinogens such as DOB and LSD. Notably, LSD does not activate IP₃ signalling through this receptor to any significant extent. This may explain why direct 5-HT2 agonists have psychedelic effects, whereas compounds that indirectly increase serotonin signalling at the 5-HT2 receptors, such as SSRIs, generally do not.

It got me thinking about something David Pearce mentioned in his Good Drug Guide (worth a read, although pretty basic for most Bluelighters) that caught my attention when I read it:

The next few decades will take us much closer to the downstream intra-cellular action. For it is here that our minds will ultimately be healed, genetically or otherwise.

[handwaving]Intuitively, I doubt that the intracellular realm is the level most relevant to conscious experience - I would imagine it lacks the spatial heterogeneity (among subregions, neuronal subtypes) of receptors, although this stuff hasn't been mapped, beacuse it's hard.[/handwaving] Most, if not all, of the drugs we know and love act at the level of the receptor, that much is certain.

So, do any of you knowledgeable folks know of any psychoactive modulator of intracellular signalling pathway constituents (e.g. kinase or phosphatase activator or inhibitor)? Lithium comes to mind, although we don't know which of its many actions are responsible for its mood-stabilising properties. Anything more dramatic out there in terms of its effect on consciousness? Any thoughts on why not, if not?

 

[sekio]

rubidium

 

[Jonneh]

rubidium

IIRC its role in treating depression was in supplementing endogenous reserves. Is it psychoactive in healthy individuals?

Any thoughts on why few drugs (and none of the ones with dramatic effects) act on the subcellular level?

 

[endotropic]

It's harder to design a drug that will pass through the cellular membrane effectively than one that will act solely on the cell surface, and intracellular signaling mechanisms tend to control really important cellular processes that you probably don't want to modulate throughout the entire body.

 

[Jonneh]

It's harder to design a drug that will pass through the cellular membrane effectively than one that will act solely on the cell surface

That's certainly true, although there are plenty of synthetic cell-permeable modulators of intracellular signalling components in existence, and nature has solved harder problems.

intracellular signaling mechanisms tend to control really important cellular processes that you probably don't want to modulate throughout the entire body.

I think this gets to the heart of the matter. In effect, we are acknowledging that the receptor level is the most pertinent for the types of changes in consciousness we are interested in. Higher up in the hierarchy (intracellular) things get too general. I guess the way things work isn't surprising - I suppose it never is, in a way.

The question, for David Pearce, will be whether brain-, region- or neuron-specific modulation of the many downstream effectors of a single receptor system in such a way as to avoid recruitment of (homeostatic) feedback loops is possible.

 

[(zonk)]

Not sure if I should've posted a TR or not but I got a chance to sample pure RbCl (Rubidium). Ordered from the most popular world famous merch site in the USA (aside from ebay)... Came from one of the few chem suppliers on there so I'm positive it's 100% legit/pure.
Opened bottle and gave it a sniff. Weirdly I felt something from the sniff, almost slightly trippy in a way? Anyway I put it away til the next day. Next day I was feeling very lethargic so I took a pinch. It tasted VERY salty, gave me a slightly noticable weird taste the persisted(barely detectable). I wasn't expecting much, figured if it was all that i would've heard more about it. I can say it definately woke my ass up. I felt like MAYBE I had taken like 1/4 an adderall sort of. I tried taking 500mg more but there was no added boost. ADD was gone and I was able to concentrate very good!
I would classify this as more of a slight modulator, it's subtle but noticable. I would say this is as much of a stimulant and Magnesium is a dissociative. Useful I guess but impossible to be recreational. Perhaps it would mix well with other substances, maybe an MAOI?

 

[Limpet_Chicken]

Bromide, for another one, KBr was for a long time used as an anticonvulsant drug, in dogs, I believe it still is. There are problems with its regular use though, as it has a ridiculously long half life, and takes an awful long time to be excreted, so, like long-acting barbiturates can build up in the body until it causes problems with regular dosing, upon which, those problems are known as 'bromism'

Never tried rubidium, interesting. Is the mechanism of action known? I would hazard a guess that it is being taken up into the intracellular environment via potassium channels, as it closely mimics K in its general chemistry, and once there is less effective at providing the inhibitory effects that K normally does. Is that something like on the mark?

 

[d1nach]

All psychoactive drugs work bt influencing intracellular signaling receptors are the primary messengers that recieve messages which it can then pass off to secondary messengers inside the cell then eventually hand off the message to your genes so they can increase abd decrease stuff based on the message