Psycho-Babble Medication Thread 1107609

Shown: posts 1 to 13 of 13. This is the beginning of the thread.

 

To SLS - clorgyline and imidazoline

Posted by linkadge on January 2, 2020, at 15:52:40

Hi SLS,

I recall you once saying that you had a good response to the drug clorgyline. I was reading about it on Wikipedia and apparently (in addition to being a potent MAOI) it is an even more potent agonist at the imidazoline receptors (in the PICOMOLAR concentration):

https://en.wikipedia.org/wiki/Clorgiline

Imidazoline receptors have been studied in depression and may have some antidepressant effect. I believe agmatine (a cheap supplement with purported antidepressant effect) is also an imidazoline agonist.

I wondered if you considered adding agmatine to your current regiment? (with or without a MAOI).

Anyhow, just an interesting finding.

Linkadge


 

Re: To SLS - clorgyline and imidazoline linkadge

Posted by SLS on January 2, 2020, at 21:20:54

In reply to To SLS - clorgyline and imidazoline, posted by linkadge on January 2, 2020, at 15:52:40

> Hi SLS,
>
> I recall you once saying that you had a good response to the drug clorgyline. I was reading about it on Wikipedia and apparently (in addition to being a potent MAOI) it is an even more potent agonist at the imidazoline receptors (in the PICOMOLAR concentration):
>
> https://en.wikipedia.org/wiki/Clorgiline
>
> Imidazoline receptors have been studied in depression and may have some antidepressant effect. I believe agmatine (a cheap supplement with purported antidepressant effect) is also an imidazoline agonist.

What do you know about the function of these receptors?

> I wondered if you considered adding agmatine to your current regiment? (with or without a MAOI).

I had never heard of agmatine until you mentioned it here. Thanks for the heads-up. The studies I found regarding agmatine are encouraging.


- Scott

 

Re: To SLS - clorgyline and imidazoline

Posted by sigismund on January 2, 2020, at 21:53:20

In reply to Re: To SLS - clorgyline and imidazoline linkadge, posted by SLS on January 2, 2020, at 21:20:54

I liked agmatine. Made me feel noticeably better.

It quickly gave me cold sores so I had to stop.

 

Re: To SLS - clorgyline and imidazoline

Posted by linkadge on January 3, 2020, at 8:05:11

In reply to Re: To SLS - clorgyline and imidazoline linkadge, posted by SLS on January 2, 2020, at 21:20:54

>What do you know about the function of these >receptors?

It doesn't appear to be a well characterized receptor (at least at the moment). There are two subtypes IM1 & IM2 but not sure of the difference. There is a binding side for imidazoline on MAO enzymes and agonizing the receptors may have some impact on monoamine oxidase levels. It also appears to regulate the alpha-2 receptors (behaving as a functional agonist) as imidazoline agonists can lower blood pressure in a clonidine sensitive manner. Imidazoline agonists may also have anti-addictive / anti-tolerance effects.

Imidazoline agonists may have antidepressant effects, but it's not conclusive as there is a lack of selective agonists for the receptor. The beta carbolines (in coffee) appear to be imidazoline agonists and MAO inhibitors.

Anyhow, not entirely sure, but there is enough evidence that imidazoline regulate certain neurotransmitter systems.

I just thought it was interesting that clorgyline was such a strong agonist at these receptors (which distinguishes it from other MAOIs) and that perhaps this could account for differences in responses to this drug.

Linkadge

 

Re: To SLS - clorgyline and imidazoline

Posted by linkadge on January 3, 2020, at 8:07:39

In reply to Re: To SLS - clorgyline and imidazoline, posted by sigismund on January 2, 2020, at 21:53:20

Yeah, agmatine did appear to help my depression, but it made my thinking a little strange. Agmatine has effects on many other neurotransmitter systems besides imidazoline including NMDA. It appears to be a very strong anti-tolerance agent and can potentiate the analgesic effects of opioids etc.

Linkadge

 

Re: To SLS - clorgyline and imidazoline

Posted by undopaminergic on January 3, 2020, at 10:35:17

In reply to To SLS - clorgyline and imidazoline, posted by linkadge on January 2, 2020, at 15:52:40

> I recall you once saying that you had a good response to the drug clorgyline. I was reading about it on Wikipedia and apparently (in addition to being a potent MAOI)
>

To be precise, it is a selective irreversible inhibitor of MAO-A. You need to follow the MAOI diet with it because the MAO in the gut is of the A isoform.

> it is an even more potent agonist at the imidazoline receptors (in the PICOMOLAR concentration):
>
> https://en.wikipedia.org/wiki/Clorgiline

The article also says it has very high (nanomolar) affinity for the sigma1-receptor, but doesn't specify whether it is an agonist or antagonist. Anyway, this action is probably of significance.

> Imidazoline receptors have been studied in depression and may have some antidepressant effect.
>

There are three known subtypes of the imidazoline receptor. Agonism at the I1-subtype has been associated with hypotensive effects. Clonidine is a mixed I1-receptor and alpha2A-adrenoceptor agonist.

https://en.wikipedia.org/wiki/Imidazoline_receptor
<<Imidazoline receptors are the primary receptors on which clonidine and other imidazolines act. There are three main classes of imidazoline receptor: I1 is involved in inhibition of the sympathetic nervous system to lower blood pressure, I2 has as yet uncertain functions but is implicated in several psychiatric conditions, and I3 regulates insulin secretion.>>

and: <<Nonselective ligands:
Agonists:
* Agmatine (putative endogenous ligand at I1; also interacts with NMDA, nicotinic, and alpha2 adrenoceptors)
* Apraclonidine (alpha2 adrenoceptor agonist)
* Cimetidine (I1 agonist, H2 receptor antagonist)
* Clonidine (I1 agonist, alpha2 adrenoceptor agonist)
* Dimethyltryptamine
* mCPP
* Moxonidine
* Oxymetazoline (I1 agonist, alpha1 adrenoceptor agonist, alpha2 partial agonist)
* Rilmenidine
* Tizanidine
>>

https://en.wikipedia.org/wiki/Idazoxan
<<... It acts as both a selective alpha2 adrenergic receptor antagonist, and an antagonist for the imidazoline receptor. Idazoxan has been under investigation as an antidepressant, ... it is under investigation as an adjunctive treatment in schizophrenia. Due to its alpha-2 receptor antagonism it is capable of enhancing therapeutic effects of antipsychotics, possibly by enhancing dopamine neurotransmission in the prefrontal cortex of the brain, ...>>

> I believe agmatine (a cheap supplement with purported antidepressant effect) is also an imidazoline agonist.
>

It is.

https://en.wikipedia.org/wiki/Agmatine
<<Mechanisms of action: Agmatine was found to exert modulatory actions directly and indirectly at multiple key molecular targets ...:
* Neurotransmitter receptors and receptor ionophores. Nicotinic, imidazoline I1 and I2, alpha2-adrenergic, glutamate NMDAr, and serotonin 5-HT2A and 5HT-3 receptors.
* Ion channels. Including: ATP-sensitive K+ channels, voltage-gated Ca2+ channels, and acid-sensing ion channels (ASICs).
* Nitric oxide (NO) synthesis modulation. Both differential inhibition and activation of NO synthase (NOS) isoforms is reported.
* NADPH oxidase. Activation of the enzyme leading to H2O2 production.
>>

and: <<Research -- Neurotransmission: Agmatine has been discussed as a putative neurotransmitter. It is synthesized in the brain, stored in synaptic vesicles, accumulated by uptake, released by membrane depolarization, and inactivated by agmatinase. Agmatine binds to alpha2-adrenergic receptor and imidazoline receptor binding sites, and blocks NMDA receptors and other cation ligand-gated channels. Short only of identifying specific ("own") post-synaptic receptors, agmatine in fact, fulfills Henry Dale's criteria for a neurotransmitter and is hence, considered a neuromodulator and co-transmitter. ...>>

and: <<Research -- Opioid liability: Systemic agmatine can potentiate opioid analgesia and prevent tolerance to chronic morphine in laboratory rodents. Since then, cumulative evidence amply shows that agmatine inhibits opioid dependence and relapse in several animal species.>>

> I wondered if you considered adding agmatine to your current regiment? (with or without a MAOI).
>

Seems to me that an exciting combination could be morphine (or other opioid) + agmatine.

-undopaminergic

 

Re: To SLS - clorgyline and imidazoline

Posted by undopaminergic on January 3, 2020, at 10:45:26

In reply to Re: To SLS - clorgyline and imidazoline, posted by linkadge on January 3, 2020, at 8:07:39

> Yeah, agmatine did appear to help my depression, but it made my thinking a little strange.
>

This pattern of "helps my depression -- BUT alas X" seems to be a recurrent theme in your experimentation. In contrast to my not unusual pattern of "BUT it stopped working", yours seems to be "BUT had X adverse effect". I don't recall ever having to stop an effective antidepressant treatment for reasons of adverse effects.

> Agmatine has effects on many other neurotransmitter systems besides imidazoline including NMDA. It appears to be a very strong anti-tolerance agent and can potentiate the analgesic effects of opioids etc.
>

Do you think it might affect stimulant (any kind but particularly amphetamine) tolerance?

-undopaminergic

 

Re: To SLS - clorgyline and imidazoline

Posted by undopaminergic on January 3, 2020, at 10:52:44

In reply to To SLS - clorgyline and imidazoline, posted by linkadge on January 2, 2020, at 15:52:40

> Hi SLS,
>
> I recall you once saying that you had a good response to the drug clorgyline.
>

I recall SLS suggested something along the lines of MAO-A inhibition being more relevant than MAO-B inhibiton with regard to *synaptic* dopamine levels.

I think he may be right, because selegiline, beyond its initial amphetaminergic effect or as a potentiator of phenylethylamine (PEA), or rasagiline, did not have any notable antidepressant effects for me.

-undopaminergic

 

Re: To SLS - clorgyline and imidazoline

Posted by PeterMartin on January 3, 2020, at 11:39:29

In reply to To SLS - clorgyline and imidazoline, posted by linkadge on January 2, 2020, at 15:52:40

I had never heard of Agmatine either. Did a quick search of Longevity and found a thread where one guy ("Jack Black") posted updates of his trial w it over a number of months (Nov '18->April '19)

https://www.longecity.org/forum/topic/103094-agmatine-miracle-supplement-or-bust/

 

Re: To SLS - clorgyline and imidazoline

Posted by linkadge on January 3, 2020, at 17:21:26

In reply to Re: To SLS - clorgyline and imidazoline, posted by undopaminergic on January 3, 2020, at 10:35:17

>To be precise, it is a selective irreversible >inhibitor of MAO-A. You need to follow the MAOI >diet with it because the MAO in the gut is of the A >isoform.

Yes. I'm aware. You don't need to rephrase / clarify everything I say.

Linkadge

 

Re: To SLS - clorgyline and imidazoline undopaminergic

Posted by linkadge on January 3, 2020, at 17:29:02

In reply to Re: To SLS - clorgyline and imidazoline, posted by undopaminergic on January 3, 2020, at 10:45:26

>This pattern of "helps my depression -- BUT alas X" >seems to be a recurrent theme in your >experimentation. In contrast to my not unusual >pattern of "BUT it stopped working", yours seems to >be "BUT had X adverse effect". I don't recall ever >having to stop an effective antidepressant >treatment for reasons of adverse effects.

Look, I save the gory details for my own personal business. I don't need to overwhelm people here with all the technical details. Also, FYI, I don't want to negatively impact other people's impressions of a medication before they take it.

So, for example...

Trimipramine. Yes it worked. However, it is also one of the genotoxic TCAs. I'm sorry, but I need a medication that I can take long term! I don't want to just get settled on a medication that I just get to respond to and then find out that it could give me cancer 20 years down the road. Sorry - deal breaker!

However, again, I don't want to give all the gory details because I don't want to negatively influence other people's response to a medication. But if you demand the details then the example I have of trimipramine is one.

So as for why I chose to stop taking agmatine - short answer - none of your business!

Linkadge

 

Re: To SLS - clorgyline and imidazoline linkadge

Posted by undopaminergic on January 4, 2020, at 8:08:41

In reply to Re: To SLS - clorgyline and imidazoline undopaminergic, posted by linkadge on January 3, 2020, at 17:29:02

> >This pattern of "helps my depression -- BUT alas X" >seems to be a recurrent theme in your >experimentation. In contrast to my not unusual >pattern of "BUT it stopped working", yours seems to >be "BUT had X adverse effect". I don't recall ever >having to stop an effective antidepressant >treatment for reasons of adverse effects.
>
> Look, ...

Hey, no need to get defensive, I'm not criticising you. In the part you cited, I was just sharing some observations. I thought I was making an interesting comparison. I concede that it may seem I was implying that you were stopping effective treatments too readily, but that was not the intention. If it was a Freudian slip, it was probably due to envy of your response rate to different agents that have failed to help me.

> So, for example...
>
> Trimipramine. Yes it worked. However, it is also one of the genotoxic TCAs. I'm sorry, but I need a medication that I can take long term! I don't want to just get settled on a medication that I just get to respond to and then find out that it could give me cancer 20 years down the road. Sorry - deal breaker!
>

No need to apologise. Thank you for explaining -- I can understand it technically, but I cannot really relate, although I *am* somewhat concerned about the implications of the fact that lamotrigine (another drug I'm taking) accumulates in the iris. Meanwhile, I'm not the least bit worried about getting cancer from trimipramine, even if I were to use it in the long term. I quit smoking, not to avoid lung cancer but to save money. I'm not afraid of death, and moreover, I do not *want* to live a long time, if life isn't better than this. Note that I'm describing my perspective, and not implying that you are more interested in quantity than quality of life. However, I wonder if you have weighed the cancer risk from trimipramine against the risk associated with untreated (or poorly treated) depression. You have said you have suicidal episodes. One of my suicidal acts would have been lethal if I hadn't received treatment as soon as I did, and I was even closer to permanent kidney failure.

> However, again, I don't want to give all the gory details because I don't want to negatively influence other people's response to a medication.
>

This cuts both ways. I am more prone to nocebo than placebo. If I think something will work great, then it almost certainly won't work at all.

However, I *am* more likely to *try* treatments that people say encouraging things about.

> But if you demand the details then the example I have of trimipramine is one.
>

Right. It was useful. In any case, your reasons are yours, and as with the example above, I probably would not share your perspective in any case. On the other hand it is interesting to see how others think different.

-undopaminergic

 

Re: To SLS - clorgyline and imidazoline

Posted by undopaminergic on January 4, 2020, at 8:13:33

In reply to Re: To SLS - clorgyline and imidazoline, posted by linkadge on January 3, 2020, at 17:21:26

> >To be precise, it is a selective irreversible >inhibitor of MAO-A. You need to follow the MAOI >diet with it because the MAO in the gut is of the A >isoform.
>
> Yes. I'm aware.

I knew you were, because you linked to the Wikipedia article. However, a lot of the rest of the readership might not be.

> You don't need to rephrase / clarify everything I say.

Of course I don't "need" to, but sometimes I'm inclined to.

-undopaminergic


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