How do the 'non-neurotoxic' releasing agents differ?

[Nagelfar]

Are any of the piperazine, aminoindane or oxazoline class of releasing agents abuseable?

Also, could there be a drug that inhibits VMAT2 reuptake without phosphorylation / reversing the action of the plasmalemmal transporters, since that is seemingly a separate mechanism?

 

[Deleted member 170540]

Benzylpiperazine, 2-aminoindane and 4-methylaminorex are all abusabe.

Don't know about VMAT2, maybe I should read more about it...

 

[Nagelfar]

Benzylpiperazine, 2-aminoindane and 4-methylaminorex are all abusabe.

Now what exactly differs in their mechanism to make them non-toxic compared to the amphetamines?

 

[Deleted member 170540]

Now what exactly differs in their mechanism to make them non-toxic compared to the amphetamines?

No idea... I think it's quite possible that no one knows that.

 

[I NUK3D U]

To answer your question specifically, this has to do with Tryptophan hydroxylase activity.

A precise mechanical answer is beyond me (and most others), as it's still only a theorectical area.

 

[rakketakke]

Benzylpiperazine, 2-aminoindane and 4-methylaminorex are all abusabe.

Don't know about VMAT2, maybe I should read more about it...

Yeah sure abuseable but non-neurotoxic 8( ?

Hasn't 4-MAR been linked with pulmonary hypertension? I'd stay clear of the aminorex series mostly...

 

[Nagelfar]

Benzylpiperazine, 2-aminoindane and 4-methylaminorex are all abusabe.

Don't know about VMAT2, maybe I should read more about it...

5,6-Methylenedioxy-N-methyl-2-aminoindane (MDMAI) looks interesting, though I've never been a fan of MDMA.

 

[altarazims]

Now what exactly differs in their mechanism to make them non-toxic compared to the amphetamines?

I thought it was (at least in part) because the wouldn't metabolize to alpha-methyldopamine?

 

[LSDMDMA&AMP]

4MAR is SOMEWHAT toxic i thought.
less so than MDMA or methamphetamine, but moreso than d-amphet/racemic phet i thought?
Wouldn't something have to do with the fact that a lot of the aminoindanes only hit 5-HT and whatnot, so theres less toxicity because theres no dopamine released at the same time?

 

[ebola?]

Hasn't 4-MAR been linked with pulmonary hypertension?

This is not neurotoxicity.

I thought it was (at least in part) because the wouldn't metabolize to alpha-methyldopamine?

1. Is ring-hydroxylation common in amphetamines without ring-substitutions?
2. It is my understanding that this process is primarily hepatic and that AMD does not readily cross the BBB, so this would not provide a strong mechanism for neurotoxicity.

4MAR is SOMEWHAT toxic i thought.

The one study I saw used methamphetamine as the comparison case, setting the bar for neurotoxicity (as indicated by depletion of intercellular DA and 5ht) rather high (as opposed to if vanilla amp were used as the comparison standard). So comparison with mildly neurotoxic compounds is an open question.

ebola

 

[ebola?]

Benzylpiperazine, 2-aminoindane and 4-methylaminorex are all abusabe.

Wait a minute. Is the mechanism of 2-aminoindane even known? Has BZP been confirmed non-neurotoxic?

ebola

 

[Deleted member 170540]

^ I have no idea why Nagelfar thinks those classes of drugs are non-neurotoxic.

 

[altarazims]

^ I have no idea why Nagelfar thinks those classes of drugs are non-neurotoxic.

The wikipedia article for 'Releasing agent' says "In contrast, piperazine, aminoindane, and oxazoline releasing agents, as well as those from various other chemical families, are considered to be either fully nontoxic, or significantly less toxic in comparison." though there is no citation for it. Maybe someone knows a source?

 

[Nagelfar]

Also, could there be a drug that inhibits VMAT2 reuptake without phosphorylation / reversing the action of the plasmalemmal transporters, since that is seemingly a separate mechanism?

Wait, would a long acting DRI with great binding affinity (enough to completely off-set coadministration of a DRA) when co-administered with a DRA have this effect? The DRA on VMAT2 reuptake, but the DRI preventing phosphorylation of plasmalemmal transporters? I'd be interested to know if such effect could be achieved and what it's outcome would be.