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Amfonelic acid II

lucifer87

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Joined
Dec 17, 2010
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God damnit I would like some more information on Amfonelic acid becuase the closed thread was VERY interesting in my opinion.

http://www.bluelight.ru/vb/showthread.php?t=253924

Now fastandbulbous, if you're reading this... have you tried Amfonelic acid?

shit, if you could email me some detailed information about experiences or give a link to them I'd greatly appreciate it. I'm doing research on various "research" chemicals and that damn Amfonelic acid caught my eye. Anyway my email is:

[email protected]

I believe I've found a source but wanted to know a little more bout the compound (and what to expect) before proceeding.

...oh, and can anyone give any references regarding fencamfamine analogs. Us americans are usually behind them euros when it comes to this shit...
 
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what's with all the shits and goddammits?
You didn't contribute anything to the last thread and the thread veered way off topic which is why it was euthanized. perhaps post something useful and interested sans shits and this thread will live.
This sub forum is called advanced drug discussion btw.
 
that's just how he talks, his email is gojesusdamnit@... lol. Goodluck gettn a reply from F&B, he's retired now, or hopefully just on hiatus. There's already detailed info regarding the experience somewhere i'm pretty sure, just gotta dig for it.
 
I'm still puzzled on why certain DRIs are considered highly recreational.

I've found coke very dissapointing, methylphenidate quite the same. Also Bupropion being a NDRI does not seem to be abusable in any way.
Why the hell is that? Is it purely cause of high selectivity.
Another thing, bit out of thread, there are tons of articles on selective reuptake inhibitors but ironically none of em elaborates where this selectivity takes place.

Could someone enlighten me on this?
 
With the phenyltropanes those that have rapid and high receptor DAT NERT occupancy are recreational, longer lasting and probably slower onset ones like CIT are not, RTI 120 for example is very rapid onset and is recreational.

It appears from the article below that he rate and amount of DAT occupancy is most important for locomotor activity in rats.

http://www.ncbi.nlm.nih.gov/pubmed/11714587

methyphenidate is recreational when snorted where the onset is rapid, 3,4-dichloro methylphenidate is much longer lasting and more potent but not considered recreational.
bupropion is a relatively low efficiency reuptake inhibitor leading to a long low increase in the monamines probably why it has limited abuse potential. I wonder about dealkylated analog it would probably be rather neurotoxic.

A few of the recreational DRI's are also releasers to an extent, things like fencamfamine appear to be able to cause DA and NE release as well as inhibiting uptake.

there is also a problem with measuring dopamine transporter occupancy because there is clear evidence that phenyltropanes bind to a site distinct from but overlapping the normal dopamine transporter site, thus it is possible to have high affinity and occupancy but limited activity on extracellular dopemine levels.
 
there are tons of articles on selective reuptake inhibitors but ironically none of em elaborates where this selectivity takes place.

Could someone enlighten me on this?

'Selectivity' denotes specificity of action upon a particular protein or chemical pathway to the exclusion of others. It is the noun form of an adjective ('selective) employing the derivational suffix. It can't "take place" anywhere. In the case of the SSRIs, the selectivity lies in their disproportionately high binding affinity for the serotonin transporter relative to most other known psychopharmacologic sites of action, for which their affinity is clinically negligible. Pretty much every paper I've ever read concerning the SSRIs mentions this, at least in passing.
 
I'm still puzzled on why certain DRIs are considered highly recreational.

I've found coke very dissapointing, methylphenidate quite the same. Also Bupropion being a NDRI does not seem to be abusable in any way.
Why the hell is that? Is it purely cause of high selectivity.
Another thing, bit out of thread, there are tons of articles on selective reuptake inhibitors but ironically none of em elaborates where this selectivity takes place.

Could someone enlighten me on this?

First: you did NOT have good coke.
Second: bupropion antagonises nAChR a3b4 and a2b4, which inhibits the reward-pathway. It's the same basic idea as taking naltrexone before drinking.
 
Ow believe me I've doe coke and crack 100s of times considring the strong trend that goes between my friends, I was offered and bought many different qualities and quantities of coke these last years still once it starts to wear off I find myself saying "I could have spent my money some other way". That's probably because 'unfortunately' the second drug that came on my path afte weed was meth at the age of 15 and I went pretty heavy on that but eventually stopped once I realized I was going psychotic.
Since then the only other stim I found just as worth was MDMA and simple amp, it's probably cause I got so accustomed to amphetamines at an eraly age and burned quite a few dopaminergic neurons with that. Coke simply does not do the trick (as of now) and even after 2-3 whole grams I'm emotionally blunted and feel like I still didn't get enough while my pals are blown out of their mind.

About SSRIs, yeah I did get that it blocks SERT though I'm still puzzled on a few matters like: why do plain SSRIs antidepressants have such a wide spectrum of efficacy and side effects from one medication to another, also as another bluelighter pointed out some time ago, why don't SSRIs show any sign of psychedelic and/or emphatogen activity at high doses. All I could think of is that they reach different concentrations in various areas of the brain and that some serotonergic pathways cancel out the stimulation on 5-HT2a/2c/1a.

Anyway, I don't want to get to off topic, DRI's surely have recreational potential, however maybe due to my heavy meth experience, the DRI's I've done so far where rather dissapointing compared to dopamine releasing agents.
 
There is rekindled interest in this material because it has become available in bulk quantities, speculation about its subjective effects and potential as a recreational drug are not needed (unless someone new has tried it (or if they have access to the original report now located on a broken link)) it has been firmly established that amfonelic acid is a rewarding stimulant. The question that needs to be addressed is the danger it might pose if it has antibiotic effects. F&B outlined some particularly nasty outcomes this could have in a previous AFA thread.
imagefly.cgi

EDIT: A quick search on pubchem yields 5,190 chemicals incorporating the 1-ethyl-4-oxo-1,8-naphthyridine-3-carboxylic acid nucleus. Several (if not all) of the analogs that have been biologically profiled possess antibacterial properties - it has been mentioned in previous threads that the antibiotics ciprofloxacin, oxolinic acid, enoxacin, and nalidixic acid also include this core structure - it is (essentially) the core of all Quinolone antibiotics. These things considered, I think it is not a question of whether AFA is an antibiotic but how potent of an antibiotic i.e. what is AFA's minimum inhibitory concentration (or whatever in vivo correlate is used in quantifying antibiotic potency). I'm not trying to scare monger and prevent this stuff from touching the market (because I'm a greedy pig) but all signs say if you get your hands on this chemical treat it as if it were AET i.e. use it once and then keep it for posterity.
 
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why do plain SSRIs antidepressants have such a wide spectrum of efficacy and side effects from one medication to another

They don't. But I can definitely understand how one could get this impression from anecdotal reports and isolated studies. Though individual trials yield wide spectra of divergent results, every meta-analysis I've read on the topic has indicated that the SSRIs are fairly homogeneous in the way of adverse and clinical effects. This is obviously notwithstanding outlying oddities, like fluoxetine's weak 5-HT2C antagonism or fluvoxamine's sigma-1 agonism, which could theoretically contribute to their clinical profile. On the other hand, I do remember frequently bumping into papers mentioning paroxetine's relatively putrid side effect load compared to others in its class, despite a lack of conspicuous pharmacologic difference. Confusing...

As for why some respond favorably to one SSRI and not to another - I'd be willing to bet that it's just a matter of interdividual variance in drug metabolism.

also as another bluelighter pointed out some time ago, why don't SSRIs show any sign of psychedelic and/or emphatogen activity at high doses.

Why would they?
 
They don't. But I can definitely understand how one could get this impression from anecdotal reports and isolated studies. Though individual trials yield wide spectra of divergent results, every meta-analysis I've read on the topic has indicated that the SSRIs are fairly homogeneous in the way of adverse and clinical effects. This is obviously notwithstanding outlying oddities, like fluoxetine's weak 5-HT2C antagonism or fluvoxamine's sigma-1 agonism, which could theoretically contribute to their clinical profile. On the other hand, I do remember frequently bumping into papers mentioning paroxetine's relatively putrid side effect load compared to others in its class, despite a lack of conspicuous pharmacologic difference. Confusing...

Those meta studies would be those that show that SSRI's are statistically no better than placebo except in severe depression, and in the case of severe depression the effect can be attributed to loss of the placebo effect? there is a clear disparity between efficacy studies that have been funded and done by the manufacturers and other studies. The manufacturer data has to show statistical significant benefits, otherwise the drug would not be licensed, yet the larger sample analyses and those not done by the manufacturer tend not to show statistically significant benefits.

I have the feeling we might see some interesting general developments big pharma has fired a lot of formerly loyal employees, some of those know some pretty dirty secrets. maybe now is the time to go long paper shredding machine manufacturers, Short big Pharma :\
 
Those meta studies would be those that show that SSRI's are statistically no better than placebo except in severe depression, and in the case of severe depression the effect can be attributed to loss of the placebo effect?

Those, yes. And a handful of other, less heavily critical ones. I assume that you're referring predominately to "Listening to Prozac but Hearing Placebo," a paper in which I place little stock due to the clear contrarian bias of the author(s), with whom I, and virtually all of biopsychiatry, have our differences. Statistical "book-cooking" is just as easy for those seeking trivial or negative results as it is for those courting monetary benefit via positive findings.

That said, I think it's been exceptionally well-demonstrated that the bulk of the SSRI's antidepressant efficacy is essentially secondary, owing largely to their anxiolytic and apathetic properties. But to shout 'active placebo' after decades of efficacious clinical use whilst hand-picking rejected studies to smooth out your line of insignificance is more than a little disingenuous, hence the controversy surrounding the paper.

The manufacturer data has to show statistical significant benefits, otherwise the drug would not be licensed, yet the larger sample analyses and those not done by the manufacturer tend not to show statistically significant benefits.

Well sure, but this is to be expected. Obvious concerns of observer bias aside, there are far more subtle confounds afoot - physician 'unblinding' following emergence of expected side effects, for instance. The importance of minimizing these all-to-common data-skewers cannot be overstated. Ergo, analyses in which scholars take a ton of dissimilar studies employing varying methods and designs (many of them unreviewed and unpublished) and lump them all into a pot with the well-funded, generally well-designed "Big Pharma" trials are inevitably going to yield garbage-quality output. After all, the input was the statistical equivalent of alphabet soup. Such was seemingly the case with Kirsch and Sapirstein.

I assure you, pharmaceutical companies are not in the business of marketing sugar pills, as it would in no way behoove them to do so, at least not in the long run. These companies dish out untold billions each year on massive R&D operations, only to have the vast majority of potential drugs either fail outright or be rejected by our governmental regulatory agencies. And while the amount of incurred revenue is inconceivably huge, the magnitude of the requisite cost is often incommensurable. Losses are consistently reported year after year. It's the rarity of the true blockbusters (yes, like Prozac) that make Big Pharma what it is - not a bloated cash cow, but a plodding workhorse, haphazardly churning out dubious products while remaining steadily afloat amid the myriad failed drugs and lawsuits, if only by the grace of its massive derivative investments and stored capital, accrued progressively over decades of consistent sales. I understand that all of the recent Pharma hate-mongering has its reasons and may perhaps be well-earned, but one must realize that if the current pharmaceutical market dies, so too goes our sole source of innovative medicine in the 21st century.
 
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I assure you, pharmaceutical companies are not in the business of marketing sugar pills, as it would in no way behoove them to do so, at least not in the long run. These companies dish out untold billions each year on massive R&D operations, only to have the vast majority of potential drugs either fail outright or be rejected by our governmental regulatory agencies. And while the amount of incurred revenue is inconceivably huge, the magnitude of the requisite cost is often incommensurable. Losses are consistently reported year after year. It's the rarity of the true blockbusters (yes, like Prozac) that make Big Pharma what it is - not a bloated cash cow, but a plodding workhorse, haphazardly churning out dubious products while remaining steadily afloat amid the myriad failed drugs and lawsuits, if only by the grace of its massive derivative investments and stored capital, accrued progressively over decades of consistent sales. I understand that all of the recent Pharma hate-mongering has its reasons and may perhaps be well-earned, but one must realize that if the current pharmaceutical market dies, so too goes our sole source of innovative medicine in the 21st century.

I used to work for one of the big 6, I know how it works, an ineffective but relatively safe drug is more desirable than a dangerous drug, of course you would want an effective safe drug but beggars can't be choosers especially if you can get a few years of extra sales by withholding data hell if you get it right those extra sales will pay the inevitable fine :\ crap that should have been killed early in the development process was pursued, longer term more speculative high risk high return stuff was ignored.

As regarding the withering and eventual loss of big pharma and the continued appearance of innovative medicine it will have little real impact. there will be a deman for innovative medicien and where there is a financially rewarding demand it will be met. What will replace it is smaller more flexible more innovative companies probably with state assistance at the regulatory approval stage. I hope that it will lead to more information openness. Big pharma like a lot of multinationals got a bit of a lucky break with the credit crunch meaning they could raise finance where the smaller companies got starved of finance, that is only a temporary reprieve.

Big pharma has drifted into 'me too' drugs and has steadily cut their proportional expenditure on R and D now less than 10% of revenue, and fired a lot of the frontline researchers and closed sites losing forever the knowledge that was walking around those sites, slick marketing now consumes much much more money than R and D. It even appears that big pharma think their future strength lies in marketing. A large proportion of the inventive stuff big pharma has at present has been bought by acquisitions of and alliances with small companies and transfer from academia some of these have proven to be highly ill considered Glaxo buying Sirtris, Roche and rnai as some recent examples.

v
 
I used to work for one of the big 6

And can I suppose that you departed their employment on less-than-cheery terms, given your concern for the multitude of layoffs? I had no idea, and I'm sorry to hear about the massive job loss in your (former?) job market of which I was completely ignorant until just now. Also, I'm not entirely clear - is this a recent trend incited by the recession, or are its motives and history predominately pernicious, as was hinted in your post?

Big pharma has drifted into 'me too' drugs and has steadily cut their proportional expenditure on R and D now less than 10% of revenue, and fired a lot of the frontline researchers and closed sites losing forever the knowledge that was walking around those sites, slick marketing now consumes much much more money than R and D.

Woah. While it may be well-known that marketing occupies one of the heftier chunks of Pharma's annual expenditure (as I did neglect to mention above), I never imagined that less than one tenth of its capital was devoted to research. Unbelievable...
 
Having taken a number of SSRIs in the past - sertraline, paroxetine, citalopram, escitalopram, as well as some non-selective SRIs - venlafaxine, clomipramine, I can say from experience (for whatever that's worth), that they do not differ much from one to the other. The only one that "felt" different to me was paroxetine, in that sense that it well... worked. It had noticeable effects on confidence and sociability for me, while the others didn't. None of them did a damn thing for obsessive-compulsive symptoms though, which is why I was prescribed them in the first place.

why don't SSRIs show any sign of psychedelic and/or emphatogen activity at high doses.

I've heard of people getting *light* psychedelic effects at high doses, and I've had some people tell me they've experienced mild visual distortions (tracers) from both therapeutic and high dose SSRI use... but overall it does seem to be quite rare, and I've definitely never heard of empathogenic effects. Anxiolytic and pro-social effects , after long term use, sure... but never empathogenic.

It does seem curious that while the effects of DRIs can be compared to dopamine releasers, the effects of SRIs do not really compare to serotonin releasers. The brain is a very complex thing.
 
http://www.ncbi.nlm.nih.gov/pubmed/2783454

"Uptake of MPP+ and dopamine into both rat and human synaptosomes was inhibited by cocaine and amfonelic acid, with the latter being five to 10 times more potent than the former. "

http://www.ncbi.nlm.nih.gov/pubmed/2572008

"Amfonelic acid (AFA), an indirect dopamine agonist, alone caused a significant dose-dependent lowering of the rewarding threshold... Since a lowering of threshold for rewarding intracranial stimulation is a model for drug-induced euphoria, the findings presented here indicate that AFA may have abuse potential. Furthermore, these results suggest that endogenous opioid systems may begin to modulate the effects of AFA on the reward system only when a certain level of activation of dopaminergic systems is reached."
perhaps this could explain or justify fastandbulbous' statement in the aforementioned thread:

http://www.bluelight.ru/vb/showthread.php?t=253924

"...almost zero peripheral effects, very euphoric effect..."

...due to our or rats' opiod systems' speculative ability to "modulate the effects of AFA on the reward system" (perhaps others which are responsible for peripheral effects too)
the definition of which I found @

http://medical-dictionary.thefreedictionary.com/biochemical+modulation

"biochemical modulation in combination chemotherapy, the use of a substance to modulate the negative side effects of the primary agent, increasing its effectiveness or allowing a higher dose to be used."

...that's to say perhaps the "almost zero peripheral effects" can somehow be attributed to one's "endogenous opiod systems" and this system's ability to "modulate the negative side effects of the primary agent", in this case AFA.
in addition to this,

http://www.ncbi.nlm.nih.gov/pubmed/2145054

“Cocaine, GBR 12909, amfonelic acid, and methylphenidate each biphasically inhibited uptake in the striatum, nucleus accumbens and olfactory tubercle with GBR 12909 and amfonelic acid being approximately 50-fold more potent than cocaine or methylphenidate.”

here, inhibition of uptake (assumingly DA, due to AFA’s selective categorization, along with GBR 12909) in the nucleus accumbens stands out to me due to it’s widely accepted (as well as disputed) status as our brain’s “pleasure center”, perhaps this is why it isn’t on the market (but don’t quote me on this), maybe it hits the sweet spot a little too hard. any laboratory rats in this muh pluckin bob damn ditch?

anyway, that was the reason for the thread, to ask fastandbulbous to tell me a third person version of an experience and to see others’ opinion of this substance.

vecktor
“...perhaps post something useful and interested sans shits and this thread will live. This sub forum is called advanced drug discussion btw.”

this post’ll rock right, v... ulva? just kidding

...i’m here all night... tip your waitresses
 
I don't see why you're bringing the opioid modulation into this..

An interesting table from Eur J Pharm 281 1995 pp195-203.

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well, it has to do with fastandbulbous's post in the first AFA thread mentioning "...almost zero peripheral effects..." because i thought that this could be responsible for the lack thereof: "modulate the negative side effects of the primary agent". also, i wanted someone to do exactly what you did, post their thoughts or rebuttal to that very comment. anyway, judging from what i've found online thus far bout this substance, it looks very promising. but i've got much more "digging" to do. the only downfall i've read on this thread is it's development as an antibiotic which could create some 'hard body' bacterial/viral infections due to them possibly building an immunity, BUT it's discontinued from what i understand and unless it's substantially similar to other antibiotics, it should be a negligible risk, if any. right? i don't know. I also want to discuss other forms this shit could maybe take, say a freebase? i'm thinking if it's name is telling then it would only need to be placed in an alkaline solvent diluted with water with a slowly increasing concentration of the alkaline substance.
 
BUT it's discontinued from what i understand and unless it's substantially similar to other antibiotics, it should be a negligible risk, if any. right? i don't know.

look at nalidixic acid

220px-Nalidixic_acid.png


and amfonelic acid

220px-Amfonelic_acid.png


substantially similar.
MIC for amfonelic acid is much higher than Nalidixic acid, but it can induce the same efflux pumps.

I also want to discuss other forms this shit could maybe take, say a freebase?

it most likely takes the form of fake cathinone-prolintane-etc containing junk from China.
 
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