Toxicity of Amfonelic acid

[dean stark]

Apologies if this has been posted before.

Amfonelic acid has been show to have similar action to amphetamine and cocaine, although there has been some doubt in regard to its safety due to its structural similarity to antibiotics like Nalidixic acid.

From "Aspects of Chemistry in the Development of 4-Quinolone Anti- S2 bacterial Agents" by G. C. Crumplin:

Studies of specially synthesized minimalist 4-quinolone molecules have shown that, while they display antibacterial activity, the antibacterial activity cannot be separated from potent activity on the CNS of animals. This link between CNS activity and antibacterial activity is highlighted in amfonelic acid (figure 3), which is classified as a CNS stimulant rather than as an antibacterial agent. This compound is less active against bacteria than are many other 4-quinolones, but studies in our laboratory on selected mammalian cell lines have shown it to be markedly more toxic to these cells than are the 4-quinolones that are more active antibacterial agents. Furthermore, it can be shown that sublethal doses induced marked changes in the pattern of proteins produced by the cell [11], thus suggesting a possible effect of 4-quinolones on gene transcription in mammalian cells. In the light of the close evolutionary relationship between the eukaryotic type II DNA topoisomerases and bacterial DNA gyrase, this observation should not be surprising.

So it appears that Amfonelic acid does have antibacterial activity, in addition to being toxic and carcinogenic.

By the way, I started a new topic because toxicity information on this compound is scarce, and there is at least one on-line vendor currently selling this apparently quite toxic substance for recreational use.

 

[Hammilton]

It's very weak as an antibiotic, I wouldn't worry about that. It's far more potent as a stimulant than as an antibiotic.

That it's toxic is absolutely no surprise. They're all more or less toxic. This certainly doesn't say that it's carcinogenic, though, and even if it is, I don't know that it's more so than most other recreational drugs. A drug like amfonelic acid isn't one that would be used every day for a long period of time, like cannabis or tobacco or opioids or depressants.

 

[atara]

If it is a stimulant that compares favorably with cocaine, it is going to get used quite a bit. That said, simply being more toxic than nalidixic acid to some mammalian cell lines is meaningless if we don't know what level it becomes toxic at and how that level compares with the level for stimulant activity. If the toxic level is far higher than the stimulant level, it is not of great concern -- and amfonelic acid is to my knowledge quite a potent DRI, requiring only ~5 mg for a strong effect.

 

[dean stark]

Fair 'nuff. I don't know much about biochemistry. I really just reacted to "markedly more toxic" and "suggesting a possible effect of 4-quinolones on gene transcription in mammalian cells".

Just wanting to blow off some of my intrigue about this "bug powder"...

 

[Hammilton]

I think nicotine analogues are better for killing bugs, but this might do.

 

[fastandbulbous]

It's very weak as an antibiotic, I wouldn't worry about that. It's far more potent as a stimulant than as an antibiotic.

I would as any antibiotic effect is going to favour the growth of bacteria with resistance to that group of antibiotics (Darwinian natural selection at it's finest) , esp if regularly used a la cocaine. The last thing we need is to be encouraging antibiotic resistant bacteria to be growing inside us; MRSA anyone...

 

[Hammilton]

I'm not sure about that. Do they not need to be present at a high enough concentration before they have an effect?

Pretend that you have 10 molecules of amfonelic acid, and 10,000 bacteria. If those ten molecules kill off a few of the bacteria, nowhere near the all, is this really creating resistance? I can see how, if you kill off 99.9% of the bacteria with an antibiotic, you end up with just the resistant ones. An obvious way to accelerate evolution.

But if you're only killing .001% you're not exactly accelerating evolution are you? I mean, sure, it's accelerating it to a tiny degree, and now we're talking about millenniums, not decades.

 

[fastandbulbous]

No the point is such conditions favour the growth of bacteria with the enzyme that 'knocks out' the antibiotics as even in low concentration, any antibiotic will slow the growth of non-resistant bacteria by interfereing in some metabolic pathway, hence the ones that grow fastest are the ones with resistance. The same effect can be seen with low concentrations of pennecillins, where bacteria without the beta-lactamase enzyme are able to grow cell walls faster than those without. In the end that leads to a population that all contain beta-lactamase and penecillins are useless against them.

That's why when taking antibiotics you're not supposed to miss out doses or stop taking them before the course is finished as it gives an advantage to the resistant bacteria (the immune system takes care of them if they're just present as a small percentage of the overall population)

But if you're only killing .001% you're not exactly accelerating evolution are you? I mean, sure, it's accelerating it to a tiny degree, and now we're talking about millenniums, not decades.

Bacteria can reproduce every 20 minutes and if you consider their exponential growth, we're not even talking decades, but possibly months (after say 5 hours, which is 15 x 20 minutes, there could potentially be 2^15 bacteria which are resistant - that's over 32 thousand bacteria in 5 hours and in another 5 hoours you'll have 32 768 x 32 768, which is over a million inless than half a day...

 

[Hammilton]

and in a month bacteria we won't be able to move around through all of the bacteria!

There's a maximum amount of bacteria that's going to be present in a non-sick person, but even in a sick person, people using pennicillin take doses that kill virtually the whole population off. Those that don't finish it off end up allowing the resistant bacteria to come back and fill in the gap.

We're talking about doses that'll be lucky to put a dent in the population, leaving a tiny gap to be filled.

Using that logic pennicillin would be useless, triclosan would be useless, etc, but they're not even close yet.

 

[fastandbulbous]

If you use sub clinical doses of penicillin for a fair while it does become useless. Large doses kill off so many bacteria that the immune system can take care of the rest.

We're talking about doses that'll be lucky to put a dent in the population, leaving a tiny gap to be filled.

If it has the fiending effect of cocaine, amphetamine etc it'll mean that some people have constant low plasma levels of the drug - a constant push in the direction of drug resistant bacteria


Anyway, my thoughts are thast long term use of amfonellic acid will end in tears (and not just due to the psychological consequences of long term use of stimulants) and probably the odd case of hard to treat infections

 

[ebola?]

off-topic:

Welcome back FandB! So glad...

ebola

 

[Limpet_Chicken]

Yes, welcome back

I wouldn't be so worried about bioassay type use of this substance, taking it once or twice, just for the experience, but regular use, as F&B says, is a recipe for something really nasty.

Good to see you haven't fucked off entirely F&B, although I certainly see why you don't want to be the bugger that has to deal with all the brain-donors who want to know how to get high snorting co-codamol or sticking tricyclics up their arse.

 

[fencamfamine]

If you use sub clinical doses of penicillin for a fair while it does become useless. Large doses kill off so many bacteria that the immune system can take care of the rest.



If it has the fiending effect of cocaine, amphetamine etc it'll mean that some people have constant low plasma levels of the drug - a constant push in the direction of drug resistant bacteria


Anyway, my thoughts are thast long term use of amfonellic acid will end in tears (and not just due to the psychological consequences of long term use of stimulants) and probably the odd case of hard to treat infections[/QUOTE?


It is a very good reason not to use this compound. Has anyone isolated the pharmocore of this class of DRI.

 

[fastandbulbous]

It's a real shame that this drug is so worrying to me as I have tried it and it is bloody lovely (very similar to fencamfamine in effects), but there are some drugs where the risk/benefit assessment means try them once just so you can speak from experience, but after that leave well alone; mephedrone & fenfluramine are two thers I put in this category