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extraordinary pharmacology

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BTW Hamilton What part of the following did you not understand?
"And if anyone here feels an intense hostility for Turin and his ideas, there's really no need to add to this thread. I started it so as to transmit these ideas to receptive minds, who hopefully can take the ball and run with it."
You've turned this thread into an ugly monument to adolescent dicksizing.
I'm not interested.
I have no concern with making you believe any of this.
 
spectrasonic said:
Dr Andrew Horsfield, of the London Centre for Nanotechnology, the UCL Department of Physics & Astronomy and one of the senior authors of the study, says: “Vibration theory has been around for a while but has lacked the answer to a crucial question: how could a biological system make the kind of measurements of vibrations which normally require a piece of lab kit like a spectroscope. This mechanism is more like swipe-card identification than a key fitting a lock.

“Back in 1996, a UCL researcher, Dr Luca Turin* revived the theory by suggesting that smell receptors acted like switches tuned to different frequencies across the vibration spectrum. When an odorant molecule with the correct vibration binds to the receptor it closes the switch and allows the electrons to flow. This signal is amplified and sent to the brain. Each molecule has a distinctive vibration pattern and therefore a unique smell. However, Turin’s proposal lacked mathematical rigour and the physical mechanism to back it up.”

In the latest UCL paper, the researchers propose a viable physical mechanism that fits with both the laws of physics and observed features of smell.

Professor Marshall Stoneham, of the London Centre for Nanotechnology, the UCL Department of Physics & Astronomy and one of the senior authors of the study, added: “The key to determining whether the vibration model works lies in the rate that electrons move around either in the presence or absence of an odour. Our calculations show that electron flow increases significantly in the presence of an odour, suggesting there’s mileage in vibration theory.

“Furthermore, this type of receptor activation, which essentially relies on ‘biological electronics’, was previously unknown and could explain how other systems in the body operate.”


Dr. Horsfield and Prof. Stoneham were however disappointed by the reaction of precocious pharmapunk genius Mr Ham Milton who was quoted as saying "I know lots about Turin's hypothesis, and about how it's been disproven. I know a few morons cling to it, but c'mon...."
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In general, (and correct me if i'm wrong here guys), I think we prefer cited literature from journals as opposed to news articles.
And I believe the reason for this preference is that news articles are:
1) Never advanced or indepth on the proofs
2) Not written by PhDs
3) Although they may quote geniuses, news articles (in general) glamorize things and, apparently, have no desire to not write things that would lead people to believe amazing shit that (frankly) isn't true—and moreover wasn't the intended ideas expressed in the real scholarly journal.

In summary, please cite more papers that are published in journals

:) You seem like a very studious person and that's a great quality to have when contributing to Advanced Drug Discussion, I hope you don't take what I'm saying as an insult, conversly, I welcome feedback/a reply from you concerning this reply of mine :)
 
And if anyone here feels an intense hostility for Turin and his ideas, there's really no need to add to this thread. I started it so as to transmit these ideas to receptive minds, who hopefully can take the ball and run with it."
You've turned this thread into an ugly monument to adolescent dicksizing.
I'm not interested. I have no concern with making you believe any of this.
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I don't feel any antiphathy for Turin or his hypothesis. I think his hypothesis was a fine one, but that's has very little to nothing to support it. I think, that based upon the little we know about olfactory receptors, his hypothesis was as good as the "key fit" theory, but in the 70-some years since the vibration hypothesis was introduced, there hasn't been anything proving it experimentally.

If you could show me what you mean by "adolescent dicksizing" I'd love to see it. Assuming that by “dicksizing” you mean the “I’m smarter than you are” sort of thing, I just can’t find any examples. As far as I can tell, I’ve limited my discussion to attacking the theory you presented. If you’re so close to it that attacking your theory is the same to you as making ad hominem attacks, then any conversation of it is meaningless. I thought the point of this thread was to discuss the merits of your ‘theory’- and finding none, I explained (repeatedly) the various reasons why it had no merit. Actually, between the two of us, you’re the only one who’s made an ad hominem attack directed toward the other.

I don’t understand what you expected when you started this thread? You didn’t have any evidence, nothing at all to support it, only the link between g-proteins being olfactory receptors and also being receptors in the brain, and then later suggested that we just take Turin’s theory and apply it to the brain as your own. Okay, so let’s also take the predictions Turin made- after all, there needs to be a biological spectroscope, and he’s provided the only plausible, detailed explanation of how that might look. We know that no such thing exists in the brain. Now what do you expect us to say?

“quasipseudoscience” sounds about right.

Adrenochrome's perfectly right about the preference to the fact-based, scholarly sources vs. news articles quoting biased scientists. When it comes to upsetting decades of accepted theory, all the studies that gave us evidence indicating that this is the way it is, of course we're going to demand some sort of evidence. Did you have the impression that we were all uneducated tweakers in here?

The only reason Turin's hypothesis had the possibility of being true was because we don't know that much about olfactory receptors. We know lots more about receptor binding in the brain, though, so it would require one hell of a bombshell for us to accept this.

Also, Bluelight has a policy (which I'm fairly certain covers this) that requires a source (a link, proper citation... I think the latter is allowed, no?) for all media quotations.
 
Ham-milton
I'm reluctant to post any reply to you as I know this will just provoke you to respond. As far as I'm concerned you've been hijacking this thread and pissing all over it in adolescent fashion in order to satisfy your own craving for attention. What? You're a grown up? And yet you feel that its appropriate in a serious and scholarly arena to label whatever you don't understand as "demented" or fit only for crackheads. You "don't feel any antiphathy(sic) for Turin or his hypothesis" and yet you describe it all as "quasipseudoscience"? I've already asked you to back off. Now kindly cease and desist until you've at least read everything at flexitral and thought long and hard over it all.
 
we interrupt this thread to make the following announcement:

people, can we bring this back on topic, otherwise vecktors' ruthless signal to noise scythe will be used.
Personal insults are not acceptable even if someone dares to have a different opinion, the whole point of discussing is that you should be able to argue your position without resorting to personal attacks. Disaggreement and unorthodoxy and maverick ideas are essential to science, homogenous consensus bullshit dogma is for comittees, politicans and global warming science.

KEEP IT CIVIL

:|
That ends the public announcement....
Back on topic

Turins theory Olefaction still requires an element of lock and key in his original paper he never proposed that there was some special receptor that looked for IR stretches and bends, rather he said that they were pretty standard G-protein coupled receptors might be activated through electron tunneling.

fundementally it doesn't matter what IR features or molecular structure the ligand possesses it is totally irrelevant if the molecule cannot get into the tunneling gap. so Turins theory cannot be a replacement for lock and key/ induced fit unless as someone pointed out there were special non shape descriminant receptors, for which there is no real evidence
I personally do not see any reason why electronic effects at the receptor cannot be part and parcel of receptor activation, however they would work in concert with lock and key.

A few quick thoughts,
take the 5ht2a receptor, there are lots of competitive ligands for the normal binding domain, most are pretty much of a muchness but we already know that there are several down stream signalling pathways. yet the ligands are so similar in shape it is difficult to see how such a slight difference in shape could cause such a radical change in receptor conformation in order to trigger a whole different cascade of downstream signalling. the two ligands I am thinking of are Lisuride and LSD.

In the late 1960s there were a series of papers on mescaline analogs which correllated HOMO to psychedelic potency ( schneider I think), and with the 245 series the correlation was pretty good.
the 245 substituted phenethylamines are perfect for electron tunneling, the 4 side chain is perpendicular to the oxygens and the lone pairs of the oxygens can act as the contacts to each side of the gap.

I can think of a couple of ways of testing the electronic hypothesis It would be good to kill it off once and for all as it has been bouncing around for over a decade, but I need to do some proper reading.
 
vecktor said:
Disaggreement and unorthodoxy and maverick ideas are essential to science, homogenous consensus bullshit dogma is for comittees, politicans and global warming science.
Click to expand...

Hurrah! Well said Vecktor
 
Again you're back to assuming I haven't gone through Flexitral's stuff years ago.

When will you please address the lack of science and the other concerns we've all raised?
 
kidamnesiac said:
post the peer-reviewed sources and evidence or else its all baloney
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thanks, that's what I was trying to say, but you did it much more efficiently.
 
Spectrasonic: Thanks for the expansion! The idea now makes much more sense, and actually caught my interest. My interpretation of the posted information is that it's a Q/SAR theory among many others. With structural biology accelerating at the moment, the validity of the proposed mechanism will probably be more easily investigated.

Please remember that it is not the 2D structure of a molecule that is the essence in SAR and Rational Drug Design. Also, I'd like to point out to all readers that we don't really know much about the inner workings of CNS receptors involved in psychopharmacology (or psychopharmacology in itself, actually).

Before I say anything more I will try to get some more information on the subject.
 
even though it may have sparked some 'antagonism' at least it makes one think which is always good -- still much to be explained and explored
 
You're the one promoting the idea, not us. We don't have the burden of disproving it.

For supposedly only having found Turin's ideas 5 days ago (4?) you're really wound up in it.

Anyway, that's a theoretical article, we're looking for something with real numbers and something to actually that this is how it works- not just one man's theory over and over again.

And I don't think anyone is asking you for evidence that it occurs in the nose- we're looking for fact-based evidence that it occurs in the brain. Like I've said over and over, with the little we know about the olfactory receptor system, Turin's hypothesis could exist in the nose (there's no experimental evidence to indicate that it does) but in the brain- there's not just no evidence to indicate that it does exist, we have enough knowlege about how the receptor system works (and knowing what receptors exist and don't) to know that the sort of receptor system that Turin's hypothesis requires doesn't exist.

It's pretty much this simple: *Turin's theory requires a set of receptors in order to work- we know that such a receptor system doesn't exist in the brain (not disproven in the nose as of yet)- either a new hypothesis for such a biological spectroscope is needed, or the concept altogether should be scrapped*

Unless you or someone else has their own hypothesis about how such a biological spectroscope exists, I don't see the point in the continuing the conversation.
 
yes that is how i saw it in that his theory MAY indeed have validity in olfactory receptor system, but it does not appear to be some all encompassing theory/hypothesis that applies to all receptor systems and appears to not be congruent to the model we have for the brain

it is still intriguing in its own right and olfatory capabilities are impressive and certainly still rquire explanation or experimental evidence, but i do not think it falls into the area of interest the predominates here which is brain neurochemistry
 
Peer Review:

A psychophysical test of the vibration theory of olfaction
Nature Neuroscience 7, 337 - 338 (2004)


Abstract:
At present, no satisfactory theory exists to explain how a given molecule results in the perception of a particular smell. One theory is that olfactory sensory neurons detect intramolecular vibrations of the odorous molecule. We used psychophysical methods in humans to test this vibration theory of olfaction and found no evidence to support it.

They tried the d-acetophenone thing and found NO evidence to support the theory.

can we kill the thread now?
 
Adrenochrome,
Dude, I don't know what to troll even means, so I strongly doubt I'm doing it, but hey, perhaps you know better.
Amnesiac bloke,
What are you the inquisitor general or something?
Since when does an idea need to be "killed" because you disagree with it?
Can't you just find another thread you feel more comfortable with?

This was the Rockefeller (8o) funded study you're referring to I presume?
 
The research was performed at the rockefeller research institute, a quite prestigious research institution. It was probably funded by the NIH.

the thread is a waste of bandwidth, the idea has no scientific backing, evidence or proof, and is merely a dressed up bastard of millions of man hours spent on SAR. It's not that I disagree with it, but what evidence is there to support it that has been published in peer-reviewed journals? (your previous link did not work) To me it is more of a crack-pot opinion/dream of a person trying to catch attention and be famous without actually doing any real science. Unfortunately these people are ubiquitous anymore.

So looking at this thread, spect. has initiated every personal attack, cursed at my lack of manners, and now is calling me a bloke? (sorry, doesn't offend us yanks.) You sure have a lot vested in this person's opinion.

Maybe you don't know what a troll is, but you are being one. I'm done with this.
 
Are you using mozilla or a similar browser? I had to switch back to the devil's work to get it to work. Even then, there was nothing about the application of that theory to neuro receptors.

The reason this thread should be closed is that it's only serving one purpose: allowing you to insult valued members for not agreeing with you.

I don't think you're another BLer dressed up in a greenlighter persona just because a BLer would know how things work around here. ADD isn't here to give meritless validation to personal hypotheses- you have to prove to us that this is indeed how it works.

Instead, you're insulting us for not agreeing with you. What did you expect? You came in here with a theory that went against everything we know about the neuroreceptors and just expected us to say, "well hey, that sounds great, I'm sure it's true" without looking for anything to actually back it up?

That's what you're asking us to do.

Since when does an idea need to be "killed" because you disagree with it?
Can't you just find another thread you feel more comfortable with?
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1. It doesn't- it should be killed because you have no data to back it up. The brain is not the nose- if you only have 'nose data' you're not confirming your hypothesis.

2. There are lots of threads we're all participating in. You may notice there are more threads than yours in here, read them and that'll prove it to you.

2b. If were were to all find new threads and avoid this one, you'd be talking to yourself- and judging from your antagonistic comments and meritless hypotheses, you're not looking for validation, just an argument.

So quit whining- we're giving you want you want.

Would you prefer if we resorted to ad hominem attacks, your style?

So looking at this thread, spect. has initiated every personal attack, cursed at my lack of manners, and now is calling me a bloke? (sorry, doesn't offend us yanks.) You sure have a lot vested in this person's opinion.
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Agreed. Hard to believe he just found Turin's hypothesis 4 or 5 days ago.

Any chance this is Turin attempting to branch out when his hypothesis found no support in the olfactory community? Is there an olfactory community?
 
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