How can a question asking what do a group of compounds have in common be put on hold because it is "too broad"?

Question

This old question (What is the mechanism of action of anaesthetics?) has recently been put on hold as being too broad.

The grounds are, apparently, that such a diverse range of compounds acting as anaesthetics must have different mechanisms of action. So the question is too broad because it would generate too many answers.

But the text of the question specifically asks why such diverse compounds appear to do the same thing, specifically "What do these heterogeneous compounds have in common". In other words why do they all act as anaesthetics?

This seems like a crazy decision for two reasons: 1 the question asked what the compounds have in common so the answer should be focussed, not a range of different things for different compounds; 2 we don't seem to know the mechanism of action and why it is different (or, to put it another way, none of the answers are specific to the compounds and none are really satisfactory).

If we had convincing mechanisms of action and they were clearly different then the "too broad" objection might make sense. But this would need to be demonstrated by answers (one of which would be "the compounds don't have anything in common"). Those who presume that the mechanisms must be different can only sustain that argument if they know the answers, which they don't seem to.

So my appeal is to stop leaping to conclusions which are irrelevant given what the question actually asked and which are based on theoretical issues nobody has the answer to.

Answer 1

So far the principal reason why this question has beed put on hold is because it is too broad. Jan's argument is that such a diverse range of compounds could not possibly have a mechanism in common (though the objections raise are theoretical and not based on any actual understanding of the scientific literature on the subject).

I find this extremely vexing. So I though I would search the actual literature for the sort of material that might constitute an answer. In doing so I discovered this quotation from the leaders of a research group I was vaguely familiar with (pubmed ref to original paper in Anaesthesiology):

The obvious mechanism suggested by our results is that general anaesthetics, despite their chemical and structural diversity, act by competing with endogenous ligands for binding to specific receptors.

Which, at the very least, suggest that the scientists who study this subject disagree with Jan's hypothesis that it is all too complicated.

Given that the original suggested mechanism for anaesthetic action was a common effect on cell membranes (also a common mechanism whereby many diverse compounds might act) this also argues that there is a real question here to answer and not something which would produce a mess of different answers for different compounds.

In short, not only is the question not "too broad" but it is a serious topic of actual scientific research by people who know what they are talking about. And reporting the answers here on chemistry.SE would be both interesting and useful.

Answer 2

I think an answer in the negative is still an answer. I think Jan's answer to this post on its own is an answer to the original question (possibly not the fully correct, specific answer, but it provides a perspective on the question). So the fact that this answer exists would mean the question isn't too broad. There are basically only two possible answers to the original question:

1. They are only coincidentally related or have an undetermined common mechanism.
2. They have a known common mechanism.

Really any question of this type would only have two answers, provided that it is narrowly focused enough (i.e. comparing a mechanism among compounds and not something like "what do methane and benzene have in common?" without any contextualizing of what factors/processes are meant to be compared).

Answer 3

The problem is that your question assumes that these compounds have something in common; that assumption is pretty much the opposite of a necessity.

The biochemical pathways in all cells are very complex. A number of regulating enzymes — both up and downregulating — are involved in the control of pretty exact concentrations of the active proteins. Most of the time these pathways are cascading pathways, meaning that the response is increased by orders of magnitude along the way. To just modify the concentration of one single ultimately acting protein, many different proteins along the regulating cascades can be attacked in different ways; further, the specific interaction between two proteins can also be a viable target.

In short, to increase the translation of one active protein, you can:

• increase the activity of every upregulating protein along all of the cascades
• inhibit the activity of every downregulating protein along all of the cascades

This shows that even though it may look like a macroscopically similar response must be due to a similar action (i.e. interaction with the same protein) on cellular level, this is not the case except in few cases.

Furthermore, just because two drugs interact with the same protein to cause the same effect does not mean that they also bind to the same site. My fuzzy recollection of the talks I heard on the antibiotic ripostatin remembers that it binds to a bacterial RNA polymerase to inhibit its function but notably using a different binding site than most other inhibitors acting on this polymerase. (I can’t remember what the other drugs were, though.)

Finally, of course, the interaction can be nonspecific or of low specificity. In this case, there is hardly any single thing that a list of nonspecific interactors have in common; they probably just find some binding site somewhere on the surface where they can interact and destroy the function of the protein affected.

Naturally, it is possible for two or more compounds to indeed interact in the same binding site. This is, however, a very unlikely case and exceedingly unlikely if the compounds have vastly different structures. If there is evidence that this is the case, please include it in the question. If it is not there, applying Occam’s razor means we should not assume any similarity.

Repeated in bullet points:

• the same physiological response does not mean that the same pathway is affected
• the same pathway does not mean the same regulation cascade is affected
• the same regulation cascade does not mean the same individual protein is affected
• the same individual protein may mean the same binding site is affected, but this is unlikely for very different compounds.

Therefore, unless you are looking for the answer ‘nothing, because they bind to different proteins and/or the interaction is nonspecific’ the question is indeed too broad in my humble opinion.