Theoretical curiosity on highly selective receptor agonist/antagonists

[Aetherius Rimor]

Are there any other highly selective agonists/antagonists similar to drugs like nalaxone is to the opiod receptors, or MDAI is to the seretonin receptors?

Assuming there exists a set of chemicals that are highly selective, and pass the blood brain barrier, wouldn't it be theoretically possible to mix/match these in such a way as to emulate the effects of any known chemical that interacts with these receptors in a similar fashion?

If proper dosage/measurements were taken to get the same level of interaction in the proper combination, it could allow us to more easily fine tune the results.

Also, with such a set of chemicals, if we were able to properly emulate known drugs, but differences were still noticed that are unattributable to metabolism of these substances being modified by them being combined, we could also discover that we are missing other interactions the emulated "known" substances have, and aid us in finding out what they are.

Just a random thought that crossed my mind, and was curious what would prevent such a scenario, or if it is possible and just not that many highly selective substances are known?

 

[endotropic]

There are plenty of chemicals that are highly selective for just one receptor, however that’s only the first condition your drugs would need for the application you’re suggesting. Just for fun, let’s put together a wishlist of all the properties your drugs would need in order to achieve what you’re talking about:

-Highly selective for one receptor subtype over any other
-Crosses the blood/brain barrier
-Metabolized by unique enzyme (only drug on the list that is metabolized by this enzyme)
-Doesn’t induce or inhibit the action of an enzyme that metabolizes other drugs on your list
-Doesn’t otherwise alter the bio-availability of any of the other drugs on your list
-All metabolites completely inactive
-Inactivated at the same rate as the drug you’re trying to emulate

And I’m sure there's more I’m missing. I doubt that any drug exists that meets all of those conditions, so no, I don’t think what you’re suggesting is possible.

 

[Aetherius Rimor]

Thank you for explaining the difficulty of the idea.

Despite the dead end this thought has reached, it does give me more pointers in things I have to study to further my self-education in this subject. I greatly appreciate it.

 

[dip12]

Combining more than two drugs to create a combined effect often starts becoming exponentially hard to predict. Pharmacokinetics (including absorption, distribution, metabolism, excretion), pharmacodynamics (receptor selectivity, interactions, side effects) need to be considered. Imagine these as variables (some known, most unknown for research chemicals) for each compound and work out the mathemathical/statistical combinations possible it becomes a very complex and unpredictable.

Bear in mind even 'selective' compounds are very rarely true selective compounds, example the 'selective' serotonin reuptake inhibitor CITALOPRAM only recently (after years of trials and clinical use) was found to effect the HERG channel thus resulting in the potential of prolonged QT syndrome at high doses (which has nothing to do with the SERT).

Pharmaceutical companies spend fortunes on not only discovering these compounds but correctly formulating them, ensuring consistency and proving safety (I.e interactions, side effects, bioavailability etc) and this is usually just for SINGLE drugs.

Creating a kind of 'pick n mix' of emotions/feelings/experiences is a nice idea (there is certainly a lot of people who attempt it) but predictability most often goes out the window simply because we don't understand anywhere near enough about these chemicals nor the human body (not even considering the potential epigenetic or genetic diversity in drug metabolism / effects)