1-Methyl-1,2,3,4-tetrahydroisoquinoline

[PinchTheBear]

Great clarification, thanks Pinch

Please let me know if you have anything to add or find any other interesting sources.

[De__eB]

The effects on NE are likely only relevant with *******, but the 5-HT2a effects would be independent.

Inb4 spiked with *******.

[CanadianChemist]

Time to orgo. chem. this thread up

Cheers.

[BigChamp89]

Time to orgo. chem. this thread up

Cheers.

awesome, gonna read this sh!t after finals

[michaelarmenta]

bump

[Unpossible]

bamp

[Unpossible]

how does a DA antagonist create stimulant effects?

does it also inhibit mao-b?

[59045]

how does a DA antagonist create stimulant effects?

good question. Is 1-MeTIQ a dopamine antagonist?

more to the point: is there evidence that this acts as a stimulant?

These effects are tissue specific as shown by its co-administrative synergistic effect with MK-801, a direct central dopamine releasing agent...

MK-801 isn't a dopamine releaser AFAIK. It's the laboratory workhorse for research into NMDA antagonists (and probably a very interesting compound)

[PinchTheBear]

MK-801 isn't a dopamine releaser AFAIK. It's the laboratory workhorse for research into NMDA antagonists (and probably a very interesting compound)

According the research I reviewed when writing this, it is, specifically in the rat pre-frontal cortex. I didn't do any research on it specifically, but it definitely has a tissue specific and dose dependent DA-related synergy going with 1-MeTIQ.

[59045]

I didn't do any research on it specifically, but it definitely has a tissue specific and dose dependent DA-related synergy going with 1-MeTIQ.

specifically: both are NMDA antagonists (though 1-MeTIQ may have a higher affinity):

J Neurochem. 2006 May;97(3):846-56. Epub 2006 Mar 3.

The mechanism of 1,2,3,4-tetrahydroisoquinolines neuroprotection: the importance
of free radicals scavenging properties and inhibition of glutamate-induced
excitotoxicity.

Antkiewicz-Michaluk L, Lazarewicz JW, Patsenka A, Kajta M, Zieminska E, Salinska
E, Wasik A, Golembiowska K, Vetulani J.

Department of Biochemistry, Polish Academy of Sciences, Cracow, Poland.
antkiew@if-pan.krakow.pl

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), unlike several other
tetrahydroisoquinolines, displays neuroprotective properties. To elucidate this
action we compared the effects of 1MeTIQ with 1,2,3,4-tetrahydroisoquinoline
(TIQ), a compound sharing many activities with 1MeTIQ (among them reducing free
radicals formed during dopamine catabolism), but offering no clear
neuroprotection. We found that the compounds similarly inhibit free-radical
generation in an abiotic system, as well as indices of neurotoxicity (caspase-3
activity and lactate dehydrogenase release) induced by glutamate in mouse
embryonic primary cell cultures (a preparation resistant to NMDA toxicity).
However, in granular cell cultures obtained from 7-day-old rats, 1MeTIQ prevented
the glutamate-induced cell death and 45Ca2+ influx, whereas TIQ did not. This
suggested a specific action of 1MeTIQ on NMDA receptors, which was confirmed by
the inhibition of [3H]MK-801 binding by 1MeTIQ. Finally, we demonstrated in an in
vivo microdialysis experiment that 1MeTIQ prevents kainate-induced release of
excitatory amino acids from the rat frontal cortex. Our results indicate that
1MeTIQ, in contrast to TIQ, offers a unique and complex mechanism of
neuroprotection in which antagonism to the glutamatergic system may play a very
important role. The results suggest the potential of 1MeTIQ as a therapeutic
agent in various neurodegenarative illnesses of the central nervous system.


PMID: 16515537 [PubMed - indexed for MEDLINE]

[PinchTheBear]

specifically: both are NMDA antagonists (though 1-MeTIQ may have a higher affinity):

Yeah I figured that's its primary mechanism, which is why it's a neuroprotectant. Thanks.

edit: I'm getting the DA info from this text: http://www.springerlink.com/content/...3/fulltext.pdf

The main finding of this paper is that an endogenous
substance, 1MeTIQ administered to rats reversed the
enhancement of MK-801-induced dopaminergic transmis-
sion in the dorsal and ventral striatum, and glutamate
release in frontal cortex.

You can see the increase yet statistically insignificant change in DA concentration with MK-801 alone:



Interestingly, and as quoted from the discussion above, the combination completely changed the respective effects on glutamate concentration, suggesting that while 1-MeTIQ may have a higher affinity for NMDA receptors, it may not produce the necessary conformational change (or perhaps only at non-physiological doses- there are only so many ways this data can contradict the in vitro study you posted, so I dunno):

[Unpossible]

Sooooooooo what's the verdict? Garbage?

[GBROS]

Its promoted as a 'mood stimulator'. Whats next? Cow dung included and disguised via its chemical structure? AX cant be trusted.

[59045]

^the substance that's the title of this thread is probably not garbage:

*free radical scavenger = good
*antiparkinson = good
*mild to moderate mao-b inhibitor = good
*neuroprotective = very good

(what did I miss?)

plus it's "natural" (in this case, found in a variety of foods and produced in the brain)

I wouldn't be surprised if it takes the edge off of amphetamine, ephedrine, methamphetamine, phentermine, diphenmetrazine, methylphenidate, DMAA and etc. (somewhat like memantine does)

I'd be curious about activity at nicotinic receptors too (just a hunch)

might 1-MeTIQ be bottled up on its own and sold as a nootropic? How much of it is in Stimulant X? Has oral BA been determined?

[59045]

from another board:

1MeTIQ does NOT have affinity at NMDAR similar to MK-801 (MK-801: Kd =1-3 nM). In fact the only study I could find showed that 1MeTIQ competed for MK-801 binding only with very high concentrations with the IC50 greater than 150 uM. This is VERY LOW. (10 uM is pushing it for significance in most cases).
This weak affinity is suspected to be at the PCP site of NMDAR as its glycine dependent and based on the structure of related compounds.

Low affinity would be expected as unsubstituted THIQ's tend to have low affinity at NMDAR. For this affinity to be significant one would need to ingest several grams and then even still?

As for any role of NMDAR affinity in its effects I have admittedly not looked into its neuroprotective effects enough to comment on this but non-NMDAR sites may be involved or very high concentrations may have been used.

source: I can't post links yet (Note: IC50 or Ki is not given (that I could find anyway) but displacement chart is shown. IC50 appears greater than 150 uM and closer to 200 uM however the format presented is not really suited for accurate determination)

Stimulants may have "affinity" at NMDAR because some authors attribute any level of displacement to affinity. Affinity unfortunately doesn't always mean significant affinity (depends how badly the lab needs grant money!!).

In regrds to stimulants with NMDAR affinity: There are reports of this. For example, Amphetamine has been claimed to bind to NMDA with low affinity. (see: I can't post links yet ). Still the monoamine releaser, uptake inhibitor actions of stimulants could override low NMDAR affinity for example but yes people are generally correct in saying that a "high affinity" antagonist of NMDA would be unlikely to be a good stimulant.

An addition factor is that NMDAR has numerous binding sites, including some that may even remain un-characterized. Antagonist activity at the known sites do typically have similar "pharmacology" but this is not completely true (for example glycine site and polyamine site antagonists). Thus one must ask where on NMDAR the affinity is for before drawing conclusions.

[-=BigSmith=-]

might 1-MeTIQ be bottled up on its own and sold as a nootropic? How much of it is in Stimulant X? Has oral BA been determined?

I know there are three companies that have licensed it for products that will be out soon. One of them will have it standalone and is a smaller company here on the boards and another is including it in their stim/weight loss formula and is a top 15 company. I think the standalone comes out within about a month.

[PinchTheBear]

from another board:

I guess this is what I couldn't put into words in post 41... affinity != agonism>signal transduction != stimulation.

What do you make of the increase (p <0.05) in glutamate concentration in synaptic space at 50mg/kg 1Me-TIQ in rats (8.5mg/kg in humans) against 1Me-TIQ + MK-801? Like, how does this relate to your theories about NMDAR binding?

[DBee]

I'll be reviewing it tomorrow:
http://forum.bodybuilding.com/showth...hp?p=635221513

[Mr_Crusher]

Guys I took 2 bottles of Slim FX and started to have the feeling that i do not belong in my own body, and I must get out... Never EVER before have had mental illness or something i quit useing it and do not have this experience again but i have symptoms of depresonalization and derealization and anxiety... Could this 1 MetiQ make me go through something like a meth withdrawal, I feel taht it has ****ed up my dopamine receptors and stuff ... any thoughts ?

[thefleshlight]

Guys I took 2 bottles of Slim FX and started to have the feeling that i do not belong in my own body, and I must get out... Never EVER before have had mental illness or something i quit useing it and do not have this experience again but i have symptoms of depresonalization and derealization and anxiety... Could this 1 MetiQ make me go through something like a meth withdrawal, I feel taht it has ****ed up my dopamine receptors and stuff ... any thoughts ?

Sounds like you're on one hell of a drug.

[Mr_Crusher]

Sounds like you're on one hell of a drug.

Slim FX - Athletic Xtreme don't take it that 1-MetiQ + slow release caffeine = ****ed up mind, never before had any mental illness. I have stopped caffeine for 6 days now and symptoms are almost completely gone, but still those stimulants are nasty

[thefleshlight]

Slim FX - Athletic Xtreme don't take it that 1-MetiQ + slow release caffeine = ****ed up mind, never before had any mental illness. I have stopped caffeine for 6 days now and symptoms are almost completely gone, but still those stimulants are nasty

Sounds like one hell of a drug.