The Large and Nifty Not-quite-advanced Drug Chemistry, Pharmacology and More Thread

[MurphyClox]

With regard to the 'grunt work' I can recommend one of ADD's finest threads, List of free chemistry databases.

It's totally undervalued (why the heck?!) but it's frequent usage would spare us a lot of useless threads at ADD.

Nonetheless, Astavats' question turned out to be quite tricky to answer. So, no prob pal, it was a pleasure to help out (even if the answer was disappointing).
I just detest such snobbish attitudes about so-called "bored theoretical drug chemists without extensive access to pharm data". Some folks are working their ass off to give this forum a meaning

- Murphy

 

[seep]

I doubt there's some secret database of 'pharm data' privy to only certain individuals. If there were, I doubt they'd be allowed to leak information from it in any case.

There are indeed secret databases: proprietary data out there that hasn't been published; some of it'll not be published anytime soon. Questions come up on this board every once in a while that I know the answer to but that I won't answer cuz there'd be a trail of crumbs. And I'm an absolute nobody, with no credentials to speak of and really not much to lose.

So imagine the amount of data that the posters here who have or will soon become credentialed and trusted professionals in the pharm industry--imagine the amount of very specific info they're privy to. Imagine a Pharm-D for Merck!

The utopia P A pines for is untenable.

 

[atara]

An own question this time:

Can somebody comment on the biological activity of "ICP" (1-(3-indolyl)-1-phenylcyclohexane), i.e. the indol-3-yl-analogue to PCP?

Active? Subjective effects?


Thanks in advance!

- Murphy

I spend the last half hour searching and I have no reason to believe any such compound has ever been synthesized. However, if you're a chemist looking to make an indolic dissociative, you may find this paper interesting...

http://www.scribd.com/doc/35753990/indolenmdaantagonists

 

[MurphyClox]

^Nope, I'm not interested in the synthesis but just the activity of this derivative.

I spend the last half hour searching and I have no reason to believe any such compound has ever been synthesized...

...which seems to be true. Looks indeed novel.

Thanks for your help anyway!

- Murph

 

[P A]

the reason why nobody answered to your question could simply be that nobody knows the answer

No shit. In what way is this contrary to my 'pathetic babble?' I'd assume that in all likelihood, someone does know the answer, just not someone who happens to post on Bluelight.ru.

Anyway, I made an exception and spend some hours (well, 2, to be exact) in search for an answer

>extensive access
>it took you two hours

yeahokaysureman

snobbish attitudes

No need to get so personally butthurt about a generalized comment regarding the apparently predominate userbase of a specific forum on a website full of discussion boards. What I said wasn't directed at anyone in particular, and was just expressing mild frustration at being ignored by a group, not you or anyone in particular. And where I come from, calling someone a chemist [or even a bored one, at that] isn't an insult. And assuming that others didn't have any higher level access than I did obviously wasn't intended as deprecating - though I'm not sure how such an observation, whether misplaced or not, could be seen as offensive by any stretch of the imagination - unless you think I was concomitantly "snobbishly" insulting myself, as I transparently present myself as having no higher-level access (journals, Medline, etc.) whatsoever. Either way, go fuck yourself.

Also, as an example, dextromethorphan/dextrorphan aren't exactly obscure drugs - for anyone with slightly more access to published literature than myself, finding the Ki data should be relatively easy, and shouldn't take long at all [definitely not "hours"]. Not to say that anyone owes me a damn thing, but it's not like I was asking for much. And believe me, using what little I had available, I did look. At a lot. For a good while. I would only ever ask such a question on a website like this as a last ditch attempt, because I don't particularly like bothering people with minutiae trivia and asking them to do a service I should be able to adequately perform myself. I usually only ask when the topic in question is of proximal importance to me or someone else. To repeat the example, while I was already curious about DXM/DXO's relative affinities, I was actually more interested in whether popular concerns regarding serotonin syndrome were warranted, and whether a friend of mine had put himself at considerable risk. I only asked after combing Google Scholar for an hour and poking around elsewhere, all of which resulted in jack shit. Being ignored while others' questions were promptly answered was annoying, and I said so, very mildly - chalking it up not to incompetence or anything personal, but to a discrepancy in fields of interest and widespread lack of access to pharm jounals [which for a layman is completely understandable]. That doesn't warrant bristling up and being a righteous prick about it.

The utopia P A pines for is untenable.

And what utopia is that? None of the questions I've asked on this board are anywhere near the academic level to which you refer, and the with the advent of the intarwebs, the majority of basic pharmaclogic data is nowadays pretty transparent, even to the general public. DXO's binding affinities? Amphetamine's mechanism(s) of action? I've read many publicly accessible abstracts of published studies directly related to those topics, a few of which hint at containing plenty of detailed data in the fulltext to which I don't always have access. My questions aren't wildly speculative or avant-garde, and secret databases be damned. seep, I appreciate the anecdote on the dark curtains and bread crumbs [a truth I can't deny], but I think that's hardly relevant to me or the questions I've asked, in this thread or in the past. Like I said, I don't think I'm asking about something completely obscure, then puling when rebuked, as Murphy and you would have it.

 

[P A]

As far as binding affinities go, why not take a look at something like the PDSP Ki database rather than asking someone to do the grunt work of looking up your stuff for you? If that's not working out for you, there's a stickied list of helpful resources that you could try, too.

If I had known about this in the first place, I might never have needed to ask. Thank you for pointing me in the right direction. And for the record, I try to answer as many questions as I ask, and do 99% of my own research (UTFSEing and such). I don't make it my life's mission to burden everyone else with 'grunt work.'

Astavats' question turned out to be quite tricky to answer

Mine, on the other hand, were just ignored.

Some folks are working their ass off to give this forum a meaning

Heroes like you, amiright Murph? I think you've adequately made your point. You can get off your self-important soapbox now.

Thanks for nothing, asshole.

 

[vecktor]

^ rather than getting pissy with each other in public take it to PM.

As for amphetamine action there are several academic review papers on the topic one I think is publically accessable, I vaguely remember posting links to one.

A more general point is that for a question to be answered it has to excite some interest in those offering the answer because usually it involves doing some research, if it doesn't excite any interest you are not going to get any answer, additionally a lot of folks do the calculation and if it looks like the exchange of information is going to be completely one sided then it is unlikely to be worth the effort.

AMPs activity is mostly synaptic MAT reversal, VMAT inhibition and weak amine effect on the vesicles.

 

[P A]

A more general point is that for a question to be answered it has to excite some interest in those offering the answer because usually it involves doing some research, if it doesn't excite any interest you are not going to get any answer

Well sure. But one would think that at least one other individual posting on a board called Advanced Drug Discussion would have some degree of intrinsic interest in discussing a specific drug on an advanced level. Aside from the admittedly boring question regarding binding affinities (the kind of question I typically shy away from asking if I can avoid it), how do my questions substantially differ from those of the "hay guise look kewl molecule" crowd? Both rely near-entirely upon intrinsic fascination and self-driven academic interest as motivation for collectively arriving at a satisfying answer. Probing deeper into amphetamine's mechanism than "it reverses the transporter, VMAT, so on and so forth" opens an array of topics for higher-level discussion for those genuinely interested, some which I directly invoked within the post in question. If you actually read my original post, I doubt you'd feel the need to introduce me to basic rules of human conversation.

 

[vecktor]

just in case you take it the wrong way my earlier post is not a personal criticism but an observation

in an ideal world questions would all get answered everyone would have access to the literature and the ability to understand the literature,That may be how it should be, but it is not how it IS. most people don't have enough time.

I did a quick google search and found http://www.lycaeum.org/research/researchpdfs/1998_kankaanpaa_1.pdf

guess what.... it describes the alterations in extracellular SE in rats, now if you had linked to that in your question and asked what correlation did it have to therapeutic or recreation amp or meth doses then that would have suggested that you had something to add....

 

[vecktor]

Well sure. But one would think that at least one other individual posting on a board called Advanced Drug Discussion would have some degree of intrinsic interest in discussing a specific drug on an advanced level. Aside from the admittedly boring question regarding binding affinities (the kind of question I typically shy away from asking if I can avoid it), how do my questions substantially differ from those of the "hay guise look kewl molecule" crowd? Both rely near-entirely upon intrinsic fascination and self-driven academic interest as motivation for collectively arriving at a satisfying answer. Probing deeper into amphetamine's mechanism than "it reverses the transporter, VMAT, so on and so forth" opens an array of topics for higher-level discussion for those genuinely interested, some which I directly invoked within the post in question. If you actually read my original post, I doubt you'd feel the need to introduce me to basic rules of human conversation.

I have next to no interest in AMP whatsoever even on an academic discussion level, the basic mechanisms have already been discovered and discussed on these very forums, IMHO it really isn't that interesting. I don't need a grand unified theory of speed.

and don't claim to have looked for the open information, you clearly haven't, I found this in 5 minutes through google scholar.

http://sulzerlab.org/pdf_articles/Sulzer05AMPHreview.pdf

 

[P A]

I have next to no interest in AMP whatsoever even on an academic discussion level, the basic mechanisms have already been discovered and discussed on these very forums, IMHO it really isn't that interesting. I don't need a grand unified theory of speed.

And that's just fine.

in an ideal world questions would all get answered everyone would have access to the literature and the ability to understand the literature,That may be how it should be, but it is not how it IS. most people don't have enough time.

I'm aware of this.

guess what.... it describes the alterations in extracellular SE in rats, now if you had linked to that in your question and asked what correlation did it have to therapeutic or recreation amp or meth doses then that would have suggested that you had something to add....

I've read that paper twice before.

And I think it was pretty clearly implied in context that I knew
that amphetamine did increase serotonin efflux at some massive IV dose in rodents (due to its comparatively low affinity for the SERT or whatever). I assumed that since this was ADD, tidbits like that would essentially be common knowledge among those toward whom the question was directed in the first place. This is why I specified human clinical dosages in the question, thereby providing a hint of purpose and utility for both the question and answer. I believe I've met my burden.

and don't claim to have looked for the open information, you clearly haven't, I found this in 5 minutes through google scholar.

I have. And of all the (literally) thousands of times I've visited Scholar, I've never once come upon any PDF or abstract on "sulzerlab.org." And yeah, I've read the abstract for that exact study dozens of times on Elsevier and its ilk, and have never been able to find the fulltext. Last time - and every time - I checked Scholar and elsewhere (and I've scoured dozens times, and like everyone else, don't have time to do so every day), a fulltext was not available for public access outside of paid subscription, something I can't afford. Either something's dramatically changed since my last search, or you didn't just 'find it.' You probably found the abstract, then used "sulzerlab" to get the fulltext, or something to that effect. Either way, thanks.

 

[P A]

I stand corrected on that. I just did a Scholar search using 'amphetamine mechanism release' as a query to find that exact study, and came up with only one link to the study you posted, the PDF link for which is worthless to me (and, by the way, is new - it wasn't there every time I searched before). My computer refuses to load from "designfiles.org," which is where I'm guessing you got the full paper. All apologies for the negligence.

 

[vecktor]

the question regarding clinical recreational doses can also be answered without using hidden literature, it just requires you to work it out.

from the lycaeum paper regarding AMP, there is an effect on extracellular serotonin at 9mg/kg rat, and a very slight effect at 3mg/kg rat, using the BSA correction factor (shown as you obviously know because you will have read the literature) to correlate to variations interspecies doses rat human conversion is 1/6 so the 9mg/kg is 1.5mg kg human, ie HED of >90mg 3mg is 30mg so the short answer is at clinical doses this study would indicate there is little or no effect on extracellular SE.

I don't ask many questions on forums, because I can usually find out the answer myself. In general the answers are all out there in the public domain, it requires a decent searching strategy and enough background knowledge to sort the wheat from the chaff. Having full literature access is nice, sure, but often it is quicker to use open access stuff. for example scholar gives you the abstracts, then web search for the file name or author and often the paper is available. IME Scholar usually beats scopus crossref and other closed literature searches. once you have a decent starting paper, it is then the old library technique of looking up the cited papers both backwards and forwards. I don't buy it when people come on these forums, say they have looked but don't cite the papers they have found even the abstracts are helpful. like I said earlier information exchange has to be mutually beneficial to work, someone with time but without full literature access can help someone with no time but full access by finding the interesting abstracts.

The sulzer AMP mechanisms paper has been available open access for a long time, I am certain I have linked to it in previous posts.

 

[UYI]

Any information available regarding:

5-Methylbutylone / 1-(benzo[d][1,3]dioxol-5-yl)-2-(dimethylamino)butan-1-one

Could anyone post a structure of this chemical please?

 

[MurphyClox]

 

[UYI]

Just to let people know that this is now being produced as a replacement for the recently banned in the uk - Butylone, cant find any information for this anywhere.

 

[P A]

the question regarding clinical recreational doses can also be answered without using hidden literature, it just requires you to work it out.

interspecies doses rat human conversion

I never appealed to any "hidden literature." And, obviously, I would be far more interested human data (were it available). Which I couldn't easily find. Which is why I asked. [And yeah, yeah, I know, amphetamine releasing agents are very similar in effect from rodent to primate, but I found some conflicting and/or ambiguous results - as in, I didn't just read one study like you did - and figured I'd ask directly].

And seriously man, I already apologized for any personal negligence [not that I really believe there was any egregious amount in the first place]. What the fuck more do you want?

I don't buy it when people come on these forums, say they have looked but don't cite the papers they have found even the abstracts are helpful.

Even if that sentence were fully intelligible, I'm not sure how much I could get out of it. You don't buy it? What, do you think I'm lying or something? Fucking ridiculous. To the same extent that many people don't have time to dig up little scraps of information for every patron of these boards all of the time, I'm not going to spend my day re-digging up information and re-hunting for abstracts after I've already searched for quite a while for what amounts to little more than a redundant formality. I articulated my questions crisply and unambiguously - what purpose could one abstract related to the topic serve? To repeat: the crowd toward whom the question was directed in the first place obviously wouldn't need a cited abstract within the question in order to discuss a possible (or the) answer. Though I had in fact read both of the abstracts to the studies you posted, I'd also read countless others. Should I have posted those as well? Or is that even what you meant 'even abstracts are helpful?' I'm not necessarily looking for fulltext papers and inline citations, just answers and discussion, like [I think] everyone else here.

And yeah, I'm fully aware of how to use Google Scholar and perform low-level academic research on the internet, as I've been doing this for quite a while; thanks.

The sulzer AMP mechanisms paper has been available open access for a long time, I am certain I have linked to it in previous posts.

Like I already said in the above post, before the other day, I had never searched Google for that particular paper, and my computer refuses to open the "designfiles" PDF link on Scholar. Mother of christ.

And what's with this bizarre undertone of condescension? "The reason you don't ask many questions?" I don't ask many questions, because, like you, I typically find the answers myself. You're a mod, so I'm sure you're more than capable of looking over all of my posts - in almost two years of being a member of this site, the only direct, academic questions I've ever posed are to be found in this sticky. Making for a total, if I remember, of four or five. Every other question I've ever asked has either been purely non-academic, fully pertinent to an ongoing in-thread discussion, and/or introduced in order to open a thread for conversation, clearly presented and phrased as such. Why is this such an issue for you? Though I had to acquire the skill on my own, I'm fully competent at hunting for open-access data, and I'll be damned if I'm going to be accosted and chided for a fault I don't have. You picked two examples of what you apparently take to be unnecessary questions - the one example was poor, for reasons I explained; the other was simply a matter of glossing over one link [that I either had forgotten about over my many searches or had never seen before] to a fulltext that my computer wouldn't even open. And, as I've already acknowledged my 'mistake' and apologized in embarrassment [as if that was even called for in the first place], why do you continue to push the issue?

 

[vecktor]

Just to let people know that this is now being produced as a replacement for the recently banned in the uk - Butylone, cant find any information for this anywhere.

It would appear that this is also covered by the generic cathinone ban in the UK, not that selling something illegal has stopped the vendors in the past

 

[vecktor]

What the fuck more do you want?

From you? nothing.

You seem to think that I am criticizing you personally, I'm not I am merely observing that the answers you seek are already out there for anyone to find.

 

[P A]

I am merely observing that the answers you seek are already out there for anyone to find.

Thanks for the observation.