chemrox - 3-4-2011 at 22:59
I should add that this is about psychoactive drugs in particular because that's the literature I've been reading and the chemistry I'm most interested
in. The community of chemists, private and academic that have worked on psychedelic drug activity have pretty much focused on receptors. The
explanation of LSD effects has pretty much centered on its role as a ligand for serotonin receptors.
If you explain psychedelic drugs this way you don't have an adequate way of explaining the difference between LSD and Mescaline as an example.
Furthermore, no matter how many receptor subtypes you invoke you still don't have an explanation of the myriad subtle differences between the indole
drugs, PEA's and amphetamines. Now more molecular platforms are being discovered as buildings for psychedelics.
An adequate theory of drug action has to explain the variety of experience just as an adequate theory of smell has to explain why chemicals smell as
they do regardless of whether they are naturally occurring or completely synthetic.
I'm suggesting that just as receptors can't adequately account for the sense of smell they won't ultimately explain the variety of drug experience.
What may help is the work being done on ion channels. What if voltage fluctuation along the sodium ion channels could be represented as a spectrum.
Sort of like an IR. Each drug would produce a unique signal made up of these voltages and these would perceived in the brain such that a unique
experience was activated.
This is pretty rough and no doubt has lots of holes in it. It's based on too little reading so far but I wanted to throw it out there in case someone
else finds it interesting or has developed a more complete view of the subject. Meanwhile I'm thinking and reading about the topic with a view
towards trying to think of an experiment or experiments to test the ideas.
I hope others will find a place to jump in either as critics or as contributors.
Attachment: 20427103-Pharm-Sodium-Channels-and-Drugs.pdf (266kB)
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UKnowNotWatUDo - 3-4-2011 at 23:49
I can understand the idea behind what you are saying, as there are so many different types of compounds that produce such a vast array of psychoactive
effects. I'm not personally familiar with any of them but I do understand how they work generally. But I think I'd have to disagree with you on the
bulk of your post. If you take into account that there are dozens of subtypes of a given receptor, each located in different densities throughout
multiple parts of the brain, and each ligand for that receptor (serotonin for example) has a unique profile of being either an agonist, antagonist,
partial agonist, or inverse agonist at each of those receptor subtypes you get a very unique fingerprint of effects. Not to mention that each subtype
of the serotonin receptor can also have different/opposite effects as the exact same subtype when it it located in a different area of the brain. A
5-HT2a receptor can be excitatory in one area but inhibitory in another. This allows compounds to deliver different effects by working off of only one
receptor. If you take into account that many of the drugs you mentioned work with multiple receptors (dopamine, serotonin, norepinephrine, etc.) then
the spectrum of effects expands even further.
Then once you also throw in the effects caused downstream in the neuronal signalling that was caused by the compound originally, as well as different
pharmacokinetics, I believe you can indeed account for all of the subtle differences between each example of seemingly similar substances.
[Edited on 4/4/2011 by UKnowNotWatUDo]
Nicodem - 4-4-2011 at 12:38
http://en.wikipedia.org/wiki/Second_messenger_system
phlogiston - 4-4-2011 at 15:15
The effect of a receptor is dictated by what cell it is located in. More often than not, receptors of any particular kind occur in many different
parts of the brain, each with their own unique function.
It is very likely that different drugs will penetrate different parts of the brain differently (local transport processes, etc.) and/or be metabolized
in different ways locally, inactivating them or giving rise to active metabolites.
Therefore, I would say it is hardly surprising that different drugs, even if they affect the same receptor, have different effects.
[Edited on 4-4-2011 by phlogiston]
[Edited on 4-4-2011 by phlogiston]