Possibility of Unfound Receptors??

[daddysgone]

This might be a terribly ignorant question, but im curious whether it is possible (likely?) that their exist unknown types of receptors in the brain which could be agonized by some substance, and ultimately evoke a psychoactive, and perhaps, novel effect.
I truly am ignorant on this matter. Has our mapping of the brain reached the point where we know of all the receptors types that exist in the brain?
Opiates bond to opiate receptors and cause a certain psychoactive response (euphoria, etc), benzos bond to GABA and cause their effects (sedation, etc). So is it possible there are whole sets of receptors of which we are not yet aware, that if properly agonized could produce psychoactive effects that perhaps we cannot even conceive? For instance, a receptor site that when agonized, produces a profound sense of deja vu. Is this possible?

 

[any major dude]

Not only possible, but likely, in my opinion. There are quite a few known 5ht receptors, but many of their actions are not entirely understood. There's a lot of unmapped territory in the brain.

 

[kaskelot]

For instance, a receptor site that when agonized, produces a profound sense of deja vu. Is this possible?

It is possible, in my experience it is not uncommon as a part of LSD effects.

 

[Hammilton]

I doubt you'll find a receptor that produces deja vu. It's just not reasonable. It's a complex mental process. You can damage sections of your brain and experience deja vu, but it's awfully unlikely that there's just one receptor that would cause this.

There are certain to be undiscovered receptors, though.

 

[pofacedhoe]

deja vu is a complex feeling and emotional memories and confusion are involved. its a high end concept compared to inhibition of impulses that occurs when certain serotonin receptors are affected by say citalopram. or when dopamine excites a person

 

[daddysgone]

thanks for the replies. i think however, that people are getting too caught up in my whole "deja vu" example. I used this as an example simply because i could not think of anything better at the moment. Basically, what im really asking, is if there are likely, yet to be discovered receptor sites, that when agonized, could produce some new and novel psychoactive effects. Again, deja vu was just an example of a novel psychoactive effect that could result. there are probably thousands of such psychoactive states, that as of now, no known activated receptors would cause.
So lets forget the deja vu thing- bad example.

But from the replies so far, it seems that most people think that there are indeed yet to be discovered receptors, that could evoke entirely new psychoactive states. Am i correct in this interpretation?

 

[Black]

Not only possible, but likely, in my opinion.

seconded. but i suspect more new receptors will be found for neuropeptides than for small molecules.

 

[mad_scientist]

Look at this template

http://en.wikipedia.org/wiki/Template:G_protein-coupled_receptors

all of the ones classified as "orphan" are genes which code for functional receptors, but neither the function of the receptor or any ligands which bind to it have been identified...so there are at least 92 new receptor targets right there!

Even if we assume that most of those uncharacterised receptors will be for non-CNS functions like regulation of tissue growth and immune system, its almost certain that at least some of them will have functions in the brain, and quite possible that some of the subset which are expressed in the brain might produce psychoactive effects if a potent and selective agonist or antagonist for that target can be found.

 

[Hammilton]

seconded. but i suspect more new receptors will be found for neuropeptides than for small molecules.

I was debating whether or not to include this exact statement, and decided against it because I wasn't sure my logic was right. I definitely agree.

 

[leungkachong]

Definitely the case that there are CNS receptors uncharacterized. If you are interested in this topic (this applies to all of you, not just daddysgone), you should do some Pubmedding on: the CB-like receptors of the hippocampus. They are definitely distinct from CB1 and CB2, but bind cannabinoids, and most likely underlie the memory-mucking effects of this class of compounds (cannabinoids mimick lesions to the hippocampus fairly well in some high dose animal models).

Furthermore, it might help to consider some of the more stranger ways in which receptor-ligand interactions can be complicated (OTHER than 2nd messengers, signal directed trafficking, etc). There is some evidence, such as antagonism @ CB receptors also antagonizing opioid receptors on the same cell and vice versa, which says that certain distinct receptor populations may exist as dimers! This would surely complicate the story, and allow for certain classes of compounds to have effects mimicking other classes only in specific functional areas.

Neuroscience is young, even though Cajal's long dead!

 

[theWorldWithin]

Yes it is highly likely, for example look into the recent discovery and research into the function of Trace Amine Receptors (TARs). This is a very interesting area right now. Now do I think we will find something new as major as say DA, SE, NE, etc. then probably not but I have been wrong many many times before so we can only hope.

Also the effects of modafanil are still very much a mystery, ripe for the possibility of a new target. Not to mention the classic highly promiscuous neuromodulators such as LSD binding to yet undiscovered targets.

Lastly I wanted to add that understanding the more subtle function of already discovered receptor subtypes can hold just as much promise as entirely new systems.

 

[daddysgone]

thanks for all the replies guys. this is turning out to be an interesting thread.
now an additional aspect of this question of unfound CNS receptors that REALLY interests me, is the types of psychoactive effects these receptors may evoke. im not nearly as interested of a newly discovered receptors that causes sedation similar to that seen in the GABA system, as i am at the prospect of newly found receptors which could possibly evoke NOVEL psychoactive effects, perhaps one which we could not even possibly conceive. That would be REALLY exciting. Imagine discovering new receptors which when activated, would cause psychoactive effects which we have never even experienced, or more likely, effects we have experienced but to a GREATLY exaggerated degree. Now that is exciting to me.

 

[any major dude]

Imagine discovering new receptors which when activated, would cause psychoactive effects which we have never even experienced, or more likely, effects we have experienced but to a GREATLY exaggerated degree. Now that is exciting to me.

the second part of your statement here would more likely be caused by discovering a more potent agonist for a known receptor & corresponding "familiar" psychedelic effect. The first part is exciting. Psychedelic trailblazing is always an exciting proposition. The real value of this type of thing, i think, would lie in being able to radio tag the new drugs to see where they bind, thus furthuring our understanding of the brain. Unfortunately the laws regarding such research are so restrictive at the moment that no research of this nature is likely to be performed in the near future.

Personally I think much could be learned by using radio labeled dmt, and its 4 & 5 subs, and comparing that to dipt, and its 4& 5 subs. Such research could greatly advance our understanding and mapping of the visual and aural centers of the brain