9 replies to this topic

[jaiho]

Agmatine produces antidepressant-like effects by activating AMPA receptors and mTOR signaling.

 

 

The activation of AMPA receptors and mTOR signaling has been reported as mechanisms underlying the antidepressant effects of fast-acting agents, specially the NMDA receptor antagonist ketamine. In the present study, oral administration of agmatine (0.1mg/kg), a neuromodulator that has been reported to modulate NMDA receptors, caused a significant reduction in the immobility time of mice submitted to the tail suspension test (TST), an effect prevented by the administration of DNQX (AMPA receptor antagonist, 2.5μg/site, i.c.v.), BDNF antibody (1μg/site, i.c.v.), K-252a (TrkB receptor antagonist, 1μg/site, i.c.v.), LY294002 (PI3K inhibitor, 10nmol/site, i.c.v.) or rapamycin (selective mTOR inhibitor, 0.2nmol/site, i.c.v.). Moreover, the administration of lithium chloride (non-selective GSK-3β inhibitor, 10mg/kg, p.o.) or AR-A014418 (selective GSK-3β inhibitor, 0.01μg/site, i.c.v.) in combination with a sub-effective dose of agmatine (0.0001mg/kg, p.o.) reduced the immobility time in the TST when compared with either drug alone. Furthermore, increased immunocontents of BDNF, PSD-95 and GluA1 were found in the prefrontal cortex of mice just 1h after agmatine administration. These results indicate that the antidepressant-like effect of agmatine in the TST may be dependent on the activation of AMPA and TrkB receptors, PI3K and mTOR signaling as well as inhibition of GSK-3β, and increase in synaptic proteins. The results contribute to elucidate the complex signaling pathways involved in the antidepressant effect of agmatine and reinforce the pivotal role of these molecular targets for antidepressant responses.

 

 

This is very interesting as Ketamine's anti depressant action was isolated to the mTOR & AMPA pathway, as well as involving GSK-3 inhibition. 

 

https://examine.com/...ments/agmatine/

 

It also has plenty of reports of it giving remission to people on Reddit, and in a small study of 2-3Grams of Agmatine a day, all patients achieved remission also. Looks very promising indeed.

 

 

Edited by jaiho, 08 November 2016 - 10:29 PM.

[Mind_Paralysis]

I will admit that it does look promising...

 

...I am a little bit skeptical about potency though - Ketamine has a really good, solid track-record, with people coming into remission - we have known about Agmatine for ages and ages... (more than a hundred years) yet in all that time, it's never been used for treating depression?

 

There's also the question of dosing - 2-3 GRAMS per day? Sounds like a lot - this implies to me that Hydroxynorketamine is far, far more potent, as Ketamine is effective in much smaller doses, and HNK is looking to be many, MANY times more potent than regular K.

 

On the other hand, Agmatine is actually available and I'm guessing the prices aren't too bad? HNK will be far away for most people for some time - Agmatine is widely available, isn't it?

[PeaceAndProsperity]

I have been taking agmatine for some time. Besides the fact that it causes terrible dizziness and physical weakness as well as other signs of poor circulation, it also seems to be able to induce depressive thinking. Agmatine "feels" like it might be able to cause some sort of schizophrenic symptoms as it's been said to possibly be relevant to (NO system in schizo).

[normalizing]

been megadosing that crap in the past. no real noticiable effect either positive or negative really. highly overrated! if that crap worked, it would be in the hands of big pharma costing you hundreds per mg. dont be fooled!

[jaiho]

been megadosing that crap in the past. no real noticiable effect either positive or negative really. highly overrated! if that crap worked, it would be in the hands of big pharma costing you hundreds per mg. dont be fooled!

 

Not really. It can't be patented.

[Ames]

With agmatine, you'll find that you'll miss your startle response (it disappears immediately) and that you'll have less of an emotional filter. For those reasons, I found it impractical to keep taking.

[fntms]

what do you mean by 'emotional filter'?

[Ames]

what do you mean by 'emotional filter'?

 

Yeah, sorry, that was vague.

 

What I mean is this: a subtle but actual side-effect seems to be that on agmatine you might have less of an ability to hold back what you might otherwise keep yourself from expressing in certain interpersonal situations.

 

ie: if you might have chosen to avoid expressing anger in a situation without agmatine, on agmatine you might instead choose to express it.

 

I read about this side-effect somewhere before I started taking it, and then found it to be a subtle but indeed present effect in my experience. Could reading about he side-effect have worked as a suggestion that manifested it? Sure. All that I can state is that, in my experience, it was present. Also, in my experience, being aware of it and telling yourself that this awareness is enough to prevent the results of the side effect is not necessarily a viable strategy.

Edited by golgi1, 13 November 2016 - 12:18 PM.

[fntms]

Thanks for the clarification, I take a small dose of agmatine daily and also notice some psychological effects which are hard to define precisely : some anxiety reduction, less inhibition, I wouldn't say more aggression (it's potentially there but stays well under control). I also notice the 'no startle' effect and perhaps less rumination.

[hnk6]

BTW: You can still join our buy-group for Hydroxynorketamine (it's a thread in the mental health forum). Just send me an e-mail: hnk6 (at) tutanota.com