5/6-apb aka 5/6-desoxy-mda neurotoxicity discussion?

[cannibalsnail]

Anyone care to speculate over the neurotoxicity of 5/6-APB?

6-APB:

5-APB:

Now in terms of monoamine release values we have the values for 6-apdb (differing by a saturated benzofuran ring) and 5-apdb (also differing in the benzofuran ring):

6-APB: IC50 values of 322 nM [SERT], 1,997 nM [DAT], and 980 nM [NET]
5-APB: IC50 values of 130 nM [SERT], 7,089 nM [DAT], and 3,238 nM [NET]

I'm unable to find the IC50 values for MDA/MDMA, if anyone has these then could they please post them?

In terms of metabolites this is pure speculation but neither of them should metabolize into α-Methyldopamine as readily but there are differing opinions on whether α-Methyldopamine is even responsible for toxicity. Anyone with a better understanding of amphetamine metabolites care to suggest what the metabolites might be and their related toxicity?

 

[Gaius]

My rat brain chart says:

MDMA IC50s: 720nM (5-HT) 1400nM (Dopamine) 660nM (Norepinephrine)

 

[ebola?]

Roughly, potential for neurotoxicity for entactogens can be thought to stem primarily from ratio of DA to 5ht release. With MDMA, the ratio is ~2:1 selectivity for 5ht, with 6apdb, ~3.2:1, with 5apdb, ~60:1 (guesstimates done in my head ). So 5apb should be negligibly neurotoxic, 6apb in league with mdma.

From here, we should try to speculate about toxic metabolites: should 6apb and 5apb catabolize to the corresponding 3,4-dihydroxy amphetamines?

ebola

 

[atara]

5-desoxy-MDA is not the same thing as 5-APB: the former is actually 5-APDB. Same for 6-desoxy-MDA.

I don't see any chance of the APBs metabolizing to catechols.

http://dmd.aspetjournals.org/content/30/12/1357.short

Benzofurans are metabolized to the homosalicylic acid, i.e. the 2-hydroxyphenylacetic acid, or to the sulfate adduct of the homosalicylol.

 

[ebola?]

5-desoxy-MDA is not the same thing as 5-APB: the former is actually 5-APDB. Same for 6-desoxy-MDA.

I know. Due to a lack of experimental data, this is what we have to generalize from.

I don't see any chance of the APBs metabolizing to catechols.

http://dmd.aspetjournals.org/content/30/12/1357.short

Benzofurans are metabolized to the homosalicylic acid, i.e. the 2-hydroxyphenylacetic acid, or to the sulfate adduct of the homosalicylol.

Thanks. Very useful. However, here, my knowledge falters: what are the chances of the formation of oxidative species, either hydroxyphenylacetic acids themselves, or products thereof via catabolism via MAO?

ebola

 

[cannibalsnail]

Would anyone happen to have a table with just RELEASE values for MDMA/MDA/MDAI/6-APB/5-APB for comparison?

 

[ebola?]

No, no one does, as the ic50 values for 5 and 6 apb at monoamine transporters are as of yet unknown.

ebola

 

[till101]

so 5-apb is (supposed to be) not neurotoxic ?

 

[sekio]

So 5apb should be negligibly neurotoxic,

Of course nobody has actually reported whether this is true, I imagine if you took a massive overdose you'd be pretty wacked out for a while.