SERT affinity MXE

[no_id]

Hey all,
I've read from various source that MXE have an affinity for SERT, ie it have serotonergic activity. I dunno at all what it mean : serotonin releaser ? SRI ?
And do this "SERT affinity" mean that taking MXE lead to perturbation of activity of a wide range of serotonin receptor or only one ? (I ask especially about 5HT2A)

I ask that mainly because I felt a distinct tripping sensation during some of my last MXE trip... (Actually it even appear that I notice it much and much, like kinda reverse tolerance, this make me fear for my sanity and toxicity of MXE - but perhaps it's only because of dose wich are higher than when I beginned with the substance).

Ive never taken 5HT2A modulator like LSD/mush or stuff, but reading some report about these substance, there is kinda similarities with some part of my experience with MXE (dissociation stay a pure MXE characteristic compared to LSD, though).

 

[sekio]

SERT is the serotonin transporter. MXE works as a SRI.

I think the NMDAr blockade is reponsible for the psychedelia though. People still trip out on ketamine, which is not a SRI.

 

[Transform]

What do you make of this:

Anesthetic (120 and 160 mg/kg. i.p.) and subanesthetic (80 mg/kg) doses of ketamine HCl were found to prevent completely the depletion of whole brain serotonin (5-HT) by p-chloramphetamine (PCA). Furthermore, ketamine HCl (160 mg/kg) completely blocked the depletion of 5-HT by PCA in every individual brain region studied (Midbrain-thalamus, hypothalamus, striatum, hippocampus and cortex). Administration of ketamine alone had no effect on brain 5-HT levels. Nialamide (a monoamine oxidase (MAO) inhibitor) and fluoxetine (a selective 5-HT uptake inhibitor) also prevented the depletion of 5-HT by PCA. However, of these three agents, only nialamide prevented the depletion of 5-HT by reserpine. These results suggest that ketamine blocks PCA-induced 5-HT depletion by inhibiting 5-HT uptake and not by inhibiting MAO. Ketamine only weakly affected either [3H]5-HT or [3H]spiroperidol binding to 5-HT1 and 5-HT2 receptors respectively even at concentrations as high as 1 mM. These data support the contention that the primary direct effect of ketamine on serotonergic systems is the blockade of 5-HT uptake and that blockade of 5-HT uptake may mediate some of the behavioral effects of ketamine, such as analgesia.

The age makes me suspicious but they do assert quite confidently.

Also Subanesthetic Doses of Ketamine Transiently Decrease Serotonin Transporter Activity: A PET Study in Conscious Monkeys.

Subanesthetic doses of ketamine, an N-methyl-D-aspartic acid (NMDA) antagonist, have a rapid antidepressant effect which lasts for up to 2 weeks. However, the neurobiological mechanism regarding this effect remains unclear. In the present study, the effects of subanesthetic doses of ketamine on serotonergic systems in conscious monkey brain were investigated. Five young monkeys underwent four positron emission tomography measurements with [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)benzonitrile ([11C]DASB) for the serotonin transporter (SERT), during and after intravenous infusion of vehicle or ketamine hydrochloride in a dose of 0.5 or 1.5 mg/kg for 40 min, and 24 h post infusion. Global reduction of [11C]DASB binding to SERT was observed during ketamine infusion in a dose-dependent manner, but not 24 h later. The effect of ketamine on the serotonin 1A receptor (5-HT1A-R) and dopamine transporter (DAT) was also investigated in the same subjects studied with [11C]DASB. No significant changes were observed in either 5-HT1A-R or DAT binding after ketamine infusion. Microdialysis analysis indicated that ketamine infusion transiently increased serotonin levels in the extracellular fluid of the prefrontal cortex. The present study demonstrates that subanesthetic ketamine selectively enhanced serotonergic transmission by inhibition of SERT activity. This action coexists with the rapid antidepressant effect of subanesthetic doses of ketamine. Further studies are needed to investigate whether the transient combination of SERT and NMDA reception inhibition enhances each other's antidepressant actions.

That was published this year and also suggests ketamine binds SERT.

Antidepressants modulate the in vitro inhibitory effects of propofol and ketamine on norepinephrine and serotonin transporter function.

Ketamine inhibits monoamine transporters expressed in human embryonic kidney 293 cells.

RESULTS: Inhibition analysis showed that ketamine significantly inhibited the uptake of all three monoamine transporters in a dose-dependent manner. The Ki (inhibition constant) values of ketamine on the norepinephrine, dopamine, and serotonin transporters were 66.8 microM, 62.9 microM, and 162 microM, respectively. Pentobarbital, a typical general anesthetic agent with no psychotic symptoms, did not affect the uptake of monoamines, however. Further, neither the glycine transporter 1 nor the glutamate/aspartate transporter was affected by ketamine, indicating that ketamine preferentially inhibits monoamine transporters.
CONCLUSIONS:
Ketamine inhibited monoamine transporters expressed in human embryonic kidney cells in a dose-dependent manner. This result suggests that the ketamine-induced inhibition of monoamine transporters might contribute to its psychotomimetic and sympathomimetic effects through potentiating monoaminergic neurotransmission.

 

[Poodles!]

You might find the ACMD's report on MXE a good read. It suggests MXE has quite a high affinity for the serotonin transporter. I wouldn't be surprised if it had a high affinity for the D2 receptor too.

https://www.gov.uk/government/uploa...chment_data/file/119087/methoxetamine2012.pdf

 

[specialspack]

SERT is the serotonin transporter. MXE works as a SRI.

I think the NMDAr blockade is reponsible for the psychedelia though. People still trip out on ketamine, which is not a SRI.

IIRC only binding and not functional studies were done, so we don't know for sure MXE is an SRI.

 

[ebola?]

wouldn't it be pretty surprising if it were a releaser though?

ebola

 

[specialspack]

wouldn't it be pretty surprising if it were a releaser though?

ebola

Could it be a substrate but a poor RI?