1-methyl-1,2,3,4-tetrahydroisoquinoline

[23536]

this is being sold as a stimulant

pubmed link to 43 studies on same

Looking at the literature, I'm perplexed. Pretty robust as a neuroprotective (NMDA antagonist). Possibly worth looking into.

But what are the subjective effects? Anyone know of experience reports?

and ps: stimulant?

 

[sekio]

From what I'm seeing on PubMed it's antidopaminergic. Combined with NMDA antagonists not really being known to be good stimulants (ketamine, dxm, pcp) and I'd say it's probably non-stimulating.

 

[crOOk]

Interesting, I had never heard of this one.
- It's endogenuous
- It antagonizes some dopamine related drug induced changes
- Some people are getting their hopes up to use it as a) a potential treatment for addiction and b) a potential medication for treatment of positive schizophrenia symptoms

In conclusion, our present results outline a significance of exogenously applied 1MeTIQ in attenuating drug-evoked relapses to cocaine as well as the direct rewarding properties of cocaine (that model the cocaine-induced "high"), but not cocaine subjective effects. Moreover, a dissociation between effects of 1MeTIQ on cocaine vs. food-maintained responding was demonstrated.

J Physiol Pharmacol. 2007 Dec;58(4):625-39.
Effects of 1-methyl-1,2,3,4-tetrahydroisoquinoline on the behavioral effects of cocaine in rats.
Filip M, Antkiewicz-Michaluk L, Zaniewska M, Frankowska M, Gołda A, Vetulani J, Przegaliński E.
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. [email protected]

The main finding of this study was demonstration for the first time of an anti-abuse effect of an endogenous compound, 1MeTIQ, and its efficiency in counteracting morphine-induced addiction in the way useful from clinical point of view. The obtained results suggested a possibility of clinical application of 1MeTIQ in morphine addiction.

J Physiol Pharmacol. 2007 Jun;58(2):235-52.
The effect of an endogenous compound 1-methyl-1,2,3,4,-tetrahydroisoquinoline on morphine-induced analgesia, dependence and neurochemical changes in dopamine metabolism in rat brain structures.
Wasik A, Romańska I, Antkiewicz-Michaluk L.
Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

In conclusions, the present study suggests that 1MeTIQ, an endogenous neuroprotective compound, exhibits also antipsychotic-like efficacy in some animal tests, and may be useful in clinical practice as a psychosis-attenuating drug in schizophrenic patients. However, 1MeTIQ did not attenuate sensorimotor gating deficit or working memory impairment evoked by MK-801 which may be served as a model of negative symptoms of schizophrenia.

Neurotox Res. 2009 Nov;16(4):390-407. Epub 2009 Aug 1.
1-Methyl-1,2,3,4-tetrahydroisoquinoline antagonizes a rise in brain dopamine metabolism, glutamate release in frontal cortex and locomotor hyperactivity produced by MK-801 but not the disruptions of prepulse inhibition, and impairment of working memory in rat.
Pietraszek M, Michaluk J, Romańska I, Wasik A, Gołembiowska K, Antkiewicz-Michaluk L.
Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343, Krakow, Poland.

 

[23536]

Interesting, I had never heard of this one.
- It's endogenuous
- It antagonizes some dopamine related drug induced changes
- Some people are getting their hopes up to use it as a) a potential treatment for addiction and b) a potential medication for treatment of positive schizophrenia symptoms

Yeah I felt the same way when I looked at the research. Apparently it's abundant in some foods, has MAOB-inhibitory qualities, has NMDA affinity comparable to dizocilpine (MK-801), is a free radical scavenger and even protects neurons from MPP+ damage. I'm looking at the possibility of co-administration with amphetamine once I figure out dosage and oral bioavailabilty.

**the fact that it's endogenous allows it to be sold as a dietary supplement in the US

 

[bufoman]

Yeah I felt the same way when I looked at the research. Apparently it's abundant in some foods, has MAOB-inhibitory qualities, has NMDA affinity comparable to dizocilpine (MK-801), is a free radical scavenger and even protects neurons from MPP+ damage. I'm looking at the possibility of co-administration with amphetamine once I figure out dosage and oral bioavailabilty.

**the fact that it's endogenous allows it to be sold as a dietary supplement in the US

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: http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2006.03756.x/abstract (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: http://www.ncbi.nlm.nih.gov/pubmed/11861810 ). 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.

 

[23536]

thanks. extremely informative post. I was looking at the qualitative data in the study you cited and had not gone beyond the abstract.

 

[bufoman]

thanks. extremely informative post. I was looking at the qualitative data in the study you cited and had not gone beyond the abstract.

No problem. It is certainly an interesting compound. I am eager to see some reports of its subjective effects.

 

[(zonk)]

So what effect precisely does this have at dopamine receptors? Is it a releaser, reuptake inhibitor, agonist, antagonist, none of the above???

 

[Pomzazed]

Now it does look like the toxic Salsolinol (Dopamine+Acetaldehyde)....

Please, i don't want methylenedioxy analog of it... looks like it can somewhat broken down to salsolinol