Existence of µ/κ/σ-reuptake inhibitors?

[endotropic]

opiate/oids work both differently than and similar to the monoamines

I also work both differently than and similar to Ho-Chi-Minh

That's intetesting, i never thought of that before. That's how the immune system works after all though. The only trouble with this theory is that the immune system works on the blood before it gets to the brain. This is ofcourse the bain of every drug user - the 1st and 2nd pass through the liver of an injested chemical, which is why so many of us turn to vaporising, snorting, injecting etc so as to bypass those bastard liver enzymes.
I like your idea though, its logically sound and could well be true, i'm certainly no authority on whats true and whats not.

Receptors on olfactory neurons work like this too. Many (most?) of the receptors in the olfactory epithelium (and there's tons of them) aren't activated by any known endogenous compound. I don't think it's completely illogical to think there could be some receptor in the brain with no endogenous ligand, present only to sense toxins reaching the brain or something like that.

 

[AlphaMethylPhenyl]

I get it. I don't know quite the difference other than that opiates/oids are long, giant peptide-chains compared to small monoamine nuerotransmitters.

Can you clear this up for me so I can learn?

 

[Swarm]

Receptors on olfactory neurons work like this too. Many (most?) of the receptors in the olfactory epithelium (and there's tons of them) aren't activated by any known endogenous compound. I don't think it's completely illogical to think there could be some receptor in the brain with no endogenous ligand, present only to sense toxins reaching the brain or something like that.

Nice post i didn't know that about the olfactory neurons. The thing is that our sense of smell is one of our best methods of detected poison (why i hold my nose while doing shots of absinthe for example, or leave a room sharpish should i smell a bacteria infested dead rat under the bed etc). So looking at it evolutionarily i tend to think: why take a chance with the brain?Why use your most important organ to detect the prescence of toxins when you can instead partition off behind a blood brain barrier and leave the job to other gate keeper organs? That said, the organism (us) still has to assume that its first line of defence will fail from time to time and should therefore have atleast some receptors in the brain to do this. I think we already know about one, the area postrema. This is a part of your brain that senses poisons and induces vomiting (this part is active every time you puke after too much booze). I'm liking this thread. This question is alot more complex then i thought at first, and yes, i've changed my position. I now feel like my argument against is an explanation ( a partial one atleast) for.

 

[neur0net]

Reuptake inhibitors are intended for abundant neuro-transmitters, especially ones that are crucial to communication and function. To my knowledge, endogenous opoids are released when they body undergoes sensations of pain. Common neuro-transmitters are released frequently and therefore benefit more from re-uptake, as re-uptake allows a build up so to speak of the neurotransmitter. Are there even any endogenous ligands for the sigma receptor? I can't seem to think of any

DMT is known to bind to the sigma receptor. that's the closest thing to an endoligand that we've been able to find (as far as I know).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947205/

 

[Swarm]

Great find.