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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.

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  • $\begingroup$ I only realised now, re-reading the question that you are misquoting me. I do not say that they must have different modes of action, I am saying that it is more likely than not they do. Furthermore, whether something is too broad or not should be determinable by the question alone and not if and when answers to it arrive. $\endgroup$ – Jan Nov 20 '17 at 7:24
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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.

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  • $\begingroup$ A followup question is, does this belong on Chemistry or Biology? (or both?) The answers on your question are very interesting, but I'm not sure how much chemistry they contain. I guess this is a question that should be put aside for now, but the scope of our site when it comes to molecular biology / chemical biology is quite poorly defined. $\endgroup$ – orthocresol Nov 20 '17 at 1:04
  • $\begingroup$ Regarding the matter at hand, though, I think that the existence of focused answers (most clearly xavier_fakerat's) is a sign that it shouldn't be closed as unclear or broad. If it was indeed too broad, then such an answer would not be possible. The contrapositive of that is: since there is such an answer, it is not too broad. I would personally be happy to reopen, but we should give it a few more days and see what people think. // One last tangential comment about closure. One close vote tends to have a cascade effect; the next four usually come in far too easily. $\endgroup$ – orthocresol Nov 20 '17 at 1:08
  • $\begingroup$ @orthocresol I think you are right that close votes come in cascades. This question was on the site for 3 years before any close votes but got 5 in a handful of days. On whether it should be on a different site: there can't be a definitive answer. I think it's chemistry, the original research I quoted was by physicists, one of the original researchers is now a structural biologist. OTOH mechanism of action of proteins is certainly chemistry and anaesthetics are certainly chemicals so it isn't clearly off topic here. $\endgroup$ – matt_black Nov 20 '17 at 1:28
  • $\begingroup$ Oh, I don't necessarily think it's off topic myself. I was just wondering where the line is drawn. Obviously, even in real life, the boundaries between traditional disciplines are becoming increasingly blurred, so as you said there probably isn't a clear-cut answer. $\endgroup$ – orthocresol Nov 20 '17 at 1:31
  • $\begingroup$ @orthocresol On the topic of drawing the line, I think that both the biology and chemistry sites have a large overlapping area and that a question like this can clearly be on topic here. (Not being active on biology.SE, I am in no position to judge its topicity there.) Also, close votes don’t necessarily always come in cascades, but the review queue will lead to a higher number of eyes resting on a question in a condensed timeframe. As is often the case with old questions, they vanish behind the horizon for most power users once they leave the first page of questions. $\endgroup$ – Jan Nov 20 '17 at 7:22
  • $\begingroup$ I’m not only talking about the timeframe in which the close votes come in, but also the likelihood of people deciding to close. @Jan $\endgroup$ – orthocresol Nov 20 '17 at 12:43
  • $\begingroup$ "Which, at the very least, suggest that the scientists who study this subject disagree with Jan's hypothesis that it is all too complicated." I assume if you were to ask these people in person, they would tell you it's complicated. It's a biological system. It's always complicated. Note that the ligands and receptors referred to in your quote are of unspecified complexity. What do these receptors do? What do these ligands do? There's no indication of the role these species play in a biological system. $\endgroup$ – Zhe Nov 20 '17 at 15:22
  • $\begingroup$ @Zhe I'm sure everyone agrees it is complicated. But many scientists also think the mechanism for anaesthetics is common across very diverse compounds. The point is that a common mechanism (even a complicated one) makes the question valid because we don't need different answers for every compound. $\endgroup$ – matt_black Nov 20 '17 at 15:27
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    $\begingroup$ The 'common mechanism' may actually be a number of different chemistries - those receptors aren't all the same, and the chemistry of binding to different receptors is almost certainly different. Besides, what else would the mechanism be but binding to receptors? $\endgroup$ – Jon Custer Nov 20 '17 at 15:48
  • $\begingroup$ @JonCuster "may actually be a number of different chemistries" is, again, a theoretical objection based on a lack of knowledge. It is possible but isn't what the research currently says. I don't think we should rule questions as too broad when the actual literature doesn't agree with your hypothesis. $\endgroup$ – matt_black Nov 20 '17 at 16:29
  • $\begingroup$ I beg to differ - the quotation you have given says nothing at all about the number of different receptors and how their chemistry is similar or different. Your argument that it isn't too broad rests on the assumption that they are not different, and you have not proven that. $\endgroup$ – Jon Custer Nov 20 '17 at 18:01
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    $\begingroup$ @JonCuster The context makes it clear that some researchers are looking for commonality in how anaesthetics act. Besides, the issue here isn't what I have to prove. I asked a question. It was put on hold. Normally you don't have to write a whole literature review to pose the question (that's why we ask them). The burden of proof for closure is on those who want to close. So far the reasons are spurious given the known research. You are arguing about issues that should be in the answers. $\endgroup$ – matt_black Nov 20 '17 at 19:38
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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).

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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.

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    $\begingroup$ Your point is still entirely theoretical. The compounds all do have something in common:" they are all anaesthetics. Hence the mystery. Hence why it is an interesting question. You assume things are some complex that no idea can possibly explain it. If the question generated a bunch of answers with clearly evidenced mechanisms and they were all different for different compounds then your objection would be valid. $\endgroup$ – matt_black Nov 19 '17 at 19:02
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    $\begingroup$ I also haven't entirely made up my mind. In this case, I might agree more with @matt_black. It would be better to provide an answer explaining (with references) that at least two of the listed compounds have different mechanisms. Otherwise, it anybody's guess. But Jan is certainly not alone in his belief the question is too broad, as four other voters agreed. In conclusion, a bit of a grey area but the community would benefit (in my opinion) of a well-referenced answer on the main site. $\endgroup$ – Linear Christmas Nov 19 '17 at 19:33
  • $\begingroup$ @matt_black That precise first point means nothing, absolutely nothing physiologically. That is what I tried to outline in this answer. It is the same general question as asking what penicillin, vancomycin and pleuromutilin have in common since they are all antibiotics, or what silver nitrate and nitric acid have in common since they both stain the skin. $\endgroup$ – Jan Nov 20 '17 at 7:15
  • $\begingroup$ I assume that there is not a single idea present to explain it on the balance of probabilities and until counterevidence is provided. In fact, you have provided that counterevidence in your answer here; that alone being included would make me change my mind. I also do not — contrary to your next point — believe that things are so complex no idea may possibly explain them. I assume that there is not one single common mechanism — again, on the balance of probabilities and until counterevidence is provided. $\endgroup$ – Jan Nov 20 '17 at 7:17
  • $\begingroup$ Finally, whether or not a question is too broad is something that should be determinable from the question itself, not waiting for answers to turn up. With the high standards we usually hold answers up to, waiting for a confirmation by multiple answers that the question is too broad is too long. Again, providing evidence that there may indeed be a common mechanism makes the question no longer too broad. $\endgroup$ – Jan Nov 20 '17 at 7:19
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    $\begingroup$ @Jan I think an answer in the negative is still an answer. So I would think this post on its own is an answer (possibly not the fully correct, specific answer, but it provides a perspective on the question). So I would think the fact that this answer exists would mean the question isn't too broad. There are basically only two possible answers to the question: 1. They are only coincidentally related or have an undetermined common mechanism. 2. They have a known common mechanism. $\endgroup$ – Tyberius Nov 20 '17 at 15:51
  • $\begingroup$ @Tyberius I consider that a very good point and probably a neutral ground both matt_black and me could agree on. May I suggest you turn it into an answer of its own? $\endgroup$ – Jan Nov 21 '17 at 6:50

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