5,6 or 6,7-methylenedioxy-alpha-methyltryptamine

[pharmakos]

any thoughts on the possible activity of this compound? i can't find anything remotely like it through google, but then again maybe i just suck at googling.

and i know this sort of thread is usually frowned upon, but i was hoping maybe someone could shed some light on why apparently no one has seriously thought about this incredibly promising looking compound? its like a combination of MDA and AMT! how can you go wrong? haha. maybe there should be an n-methyl too?

 

[MeDieViL]

AMT allready is a powerfull serotonin releaser it wont have the same effect as adding a methylenedioxy group to (meth)amphetamine.

Apart from that my knowledge about this is too limited to get an idea about this compound.

 

[dread]

apparently no one has seriously thought about this incredibly promising looking compound?

Because it's not promising looking at all. Mainly because tryptamines do not work the same as phenethylamines.

Check out tihkal for several 5,6-MDO-tryptamines. They are mostly void of activity or otherwise disappointing.

6,7-MDO-AMT would be likely to metabolize into 6,7-dihydroxy-AMT, which is uncomfortably close to 5,7-dihydroxy-tryptamine which is a strong serotonergic neurotoxin. With an alphamethyl there it would probably be even worse.

 

[pharmakos]

Check out tihkal for several 5,6-MDO-tryptamines. They are mostly void of activity or otherwise disappointing.

the 5,6-mdo compounds in tihkal were never tested up to active levels. they were all abandoned at <25mg. i'm fairly sure that they will show activity at higher dosages. the one that interests me most from tihkal is 5,6-MDO-MIPT. still, i think MDO analogues of AMT would hopefully be promising. =/

 

[ebola?]

How can you be sure without tasting or theorized SAR beyond analogy with substituted amphetamines?

ebola

 

[Rectify]

According to wikipedia, a closely related drug, 5,6-MDO-DMT, is in TiHKAL and was only tested up to 5 mg, where it was not active.

That's not to say 5,6-MDO-AMT is inactive but at what dose, if any, its effects might be or might not be felt is anyone's guess, unless they have in the past or do (in the future) synthesize it and test it out.

5-MeO-AMT has been found to be highly potent, highly toxic, and generally, according to most but not all reports, unpleasant.

 

[NeuroPsyence]

...

 

[Indole]

^ I would assume that because 4,5-dihydroxy-AMT is metabolized into a neurotoxin, 5,6-dihydroxy-AMT or 6,7-dihydroxy-AMT would follow a similar metabolic pathway and become a reactive diol species.

There are several studies outlining the neurotoxic effects of 5,7-dihydroxy-tryptamine in rats:

Monoaminergic denervation of the rat hippocampus: microiontophoretic studies on pre- and postsynaptic supersensitivity to norepinephrine and serotonin.
De Montigny C, Wang RY, Reader TA, Aghajanian GK.
Abstract

The responsiveness of hippocampal CA3 pyramidal neurons to microiontophoretic applications of serotonin (5-HT), norepinephrine (NE), gamma-aminobutyric acid (GABA) and isoproterenol (ISO) was assessed in rats following 5,7-dihydroxy-tryptamine (5,7-DHT) and 6-hydroxydopamine (6-OHDA) pretreatments and bilateral locus coeruleus lesions. The intraventricular administration of 200 micrograms (free base) of 5,7-DHT and of 6-OHDA produced 89% and 93% decreases of 5-HT and NE respectively. None of these pretreatments modified the inital responsiveness to, or recovery from iontophoretic application of 5-HT. In 6-OHDA pretreated and locus-lesioned rats, the initial effectiveness of NE was not altered but its effect was markedly prolonged. However, there was no such prolongation of the effect of ISO which is not a substrate for the high affinity NE reuptake. The effect of GABA was not affected by these pretreatments. Acute pharmacological blockade of the NE reuptake with desipramine (5 mg/kg, i.p.) similarly induced a prolongation of the effect of iontophoretically applied NE, while fluoxetine (10 mg/kg, i.p.) a 5-HT reuptake blocker, failed to alter the recovery of pyramidal cells from iontophoretic application of 5-HT. It is concluded that 5-HT denervation induces neither pre- nor postsynaptic types of supersensitivity in hippocampal pyramidal cells, contrasting with the previously shown supersensitivity of ventral lateral geniculate and amygdaloid neurons following 5-HT denervation. NE denervation fails to induce a postsynaptic type of supersensitivity but leads to a marked prolongation of the response to NE indicative of a presynaptic mechanism. These results underscore the necessity for regional studies of neurotransmitters and drug action.

The effect of unilateral neurotoxic lesions to serotonin fibres in the medial forebrain bundle on the metabolism of [3H]DOPA in the telencephalon of the living rat.
Cumming P, Ljubic-Thibal V, Laliberté C, Diksic M.
Source

Montreal Neurological Institute, McGill University, Canada.
Abstract

We used quantitative autoradiography to measure the contribution of the 5-hydroxytryptamine (5-HT, serotonin) innervation of rat telencephalon to the synthesis of dopamine (DA) from exogenous L-DOPA. One week after stereotaxic infusions of 5,7-dihydroxy-tryptamine (5,7-DHT, 1.6 micrograms) into the right medial forebrain bundle (MFB), rats received [3H]DOPA (200 microCi,i.v.), which circulated for 90 min. The specific bindings in vitro of the 5-HT uptake site ligand [3H]citalopram and the DA uptake site ligand [125I]RTI-55 were measured in cryostat sections from the prosencephalon. In most structures ipsilateral to the lesion, [3H]citalopram specific binding was substantially reduced (50-90%). In the lateral habenula specific binding declined by only 30-40%, reflecting the presence of a 5-HT pathway deviating from the MFB at the mesencephalic flexure. [125I]RTI-55 binding in the basal ganglia was reduced by 50% on the side of the 5,7-DHT lesion, but was unperturbed in rats pretreated with desmethylimipramine (DMI). 5,7-DHT infusions decreased the synthesis of [3H]DA from [3H]DOPA in vivo in the basal ganglia by (40-90%). Pretreatment with DMI protected [3H]DA synthesis in the basal ganglia, but not in the olfactory tubercle and amygdala ipsilateral to the lesion. Whereas the 5-HT innervation does not contribute greatly to [3H]DA synthesis in the basal ganglia, a substantial proportion of [3H]DA synthesis in olfactory tubercle and amygdala requires an intact 5-HT innervation.

Phenethylamine SAR rarely correlates with tryptamine SAR, so I would be surprised if this compound would be especially active, if active at all. There line between psychoactive drug and neurotoxin is blurred, and in my opinion this compound is straddling that line too much for comfort.