Why is DOB-DragonFLY so toxic?

[Nexus_Tripper]

DOB-DragonFLY is significantly more toxic than its non-furan counterpart, DOB, while 2C-B-FLY isn't known to be more harmful than 2C-B. Why is this? Is it that the furan rings are double-bonded? I suppose that to answer this, more compounds would have to be made and nibbled. If 2C-B-DragonFLY would turn out to be much more dangerous than 2C-B or 2C-B-FLY, then the double bond would seem to be the issue. But if 2C-B-DragonFLY is as safe as 2C-B or 2C-B-FLY, the answer would still be unknown.

 

[endotropic]

I thought that cases of bromo-dragonfly toxicity usually related to mistaking the drug for a much less potent hallucinogen, leading to massive overdoses. It also has a rather excessive duration of action, which can make minor toxicities much more serious as they persist that much longer.

So based on my understanding bromo-dragonfly doesn't have any unusually toxic effects, just an unusually high potency and duration that makes mistakes much more serious.

 

[Nexus_Tripper]

I thought that cases of bromo-dragonfly toxicity usually related to mistaking the drug for a much less potent hallucinogen, leading to massive overdoses.

While it is true that most, if not all, lethal DOB-DragonFLY overdoses were due to a misidentified substance, the doses that killed people weren't all that high, certainly not "massive". 10mg of DOB-DragonFLY has been deadly. Assuming 2x potency for DOB-DragonFLY versus DOB, 10mg of DOB-Dragonfly should have been equal to 20mg of DOB. While 20mg of DOB would likely be extremely unpleasant, it would not be lethal.

 

[nAON]

A lot of psychedelics aren't full-agonists at 5HT receptors, so the side effects don't scale linearly with dose and hit a ceiling at a certain point (eg. how it's almost impossible to OD on acid). Not sure what the deal is with BromoDFLY but may factor in when making comparisons.

 

[Nexus_Tripper]

A lot of psychedelics aren't full-agonists at 5HT receptors, so the side effects don't scale linearly with dose and hit a ceiling at a certain point (eg. how it's almost impossible to OD on acid). Not sure what the deal is with BromoDFLY but may factor in when making comparisons.

LSD is a super agonist at 5HT1A. It's stronger than a full agonist at some 5HT receptors yet it is safe.

 

[adder]

This is only an idea, but I suppose those two additional aromatic rings possibly make it bind strongly to monoamine transporters and potentially fatal side effects may occur much faster than with 2C-B-FLY for instance. Perhaps it's a similar type of relation as seen between MDMA and benzofurans with the latter having a steeper dose-response curve. You can find quite a lot of potent stimulants with an additional aromatic ring (naphthylisopropylamine, naphyrone, methylnaphthidate - all of them generally have a boosted affinity vs. the phenyl analogue for monoamine transporters, especially SERT), so some additional pi stacking interaction probably happens.

 

[nAON]

LSD is a super agonist at 5HT1A. It's stronger than a full agonist at some 5HT receptors yet it is safe.

1A is regulatory though, activation here effectively antagonizes effects at other 5HT receptors. Most of the side effects come from 2B I think. Indeed it may be that ratio of 1A/2 binding may affect side effect profile, ie. a drug that hits 1A as much as 2 would have fewer side effects than one that's selective for 2.

 

[ebola?]

The short answer is that we don't know. A good hypothesis is that there is something about strong, broad-specturm full 5ht2 agonism that leads to cardiotoxicity, in particular dangerous levels of vasoconstriction.

ebola

 

[Solipsis]

No we don't know, but I would suggest that rarely a single feature of a molecule would be the culprit. Rather it is the idiosyncratic properties even if they are composed in some way SARs investigate.

In the case of BDFLY my suspicion would be that it is the combination of high pharmacological efficacy combined with metabolism resistant moiety application like alpha-alkylation and polycyclic constriction; but also especially possible agonism of serotonergic receptors of various subtypes.
The wrong assumption always seems to be that side-effects must come from the receptor types other than the one we hold responsible for the main effect...

It was pointed out to me that DOX stimulation issues are probably not analogous to those with amphetamine stims... Even if DOX technically are ones (amps).

Similarly NBOMe toxicity has been suggested to exist due to reasons even closer to home than expected: namely rather intrinsic to the effects.

If you must know I think high selectivity and efficacy drugs may not necessarily be where it's at.
Most drugs have an effect that gets the mercy of being balanced and attenuated. As with cannabinoids, we can use the cushioning IMO.
It may actually be more conductive to keeping equilibria that are important in our brain function.

 

[blueberries]

I wonder if DOB-FLY would act differently. Maybe 2C-B-DragonFLY holds similar toxicity at parallel doses. This is something I'd quite like to see though; 2C-B-DragonFLY. I'm surprised it hasn't been explored by now.