Psycho-Babble Medication Thread 1106750

Shown: posts 1 to 25 of 37. This is the beginning of the thread.

 

What do TRD patients take without an MAIO

Posted by PCB on November 10, 2019, at 18:06:06

Hey Everyone,

Still plodding my way to find an alternative to nardil. Many psychiatrist do not prescribe MAOIs. Less then 1% of the prescribed antidepressants in the US are MAOIs.

So most likely a majority of treatment resistant patients are never are offered Nardil, Parnate. Do think they end up on ECT, TMS? How can so many of us only respond to MAOIs, yet they are rarely prescribed?

PCB

 

Re: What do TRD patients take without an MAIO

Posted by Christ_empowered on November 10, 2019, at 21:16:41

In reply to What do TRD patients take without an MAIO, posted by PCB on November 10, 2019, at 18:06:06

it depends. 'depression' covers a lot of ground, obviously. also depends on history, the prescriber, insurance coverage issues, etc.

what i've seen....

seroquel+upper (in my acquaintance's case, adderall).

what i'd call a 'modified goof ball' : upper, downer, neuroleptic or antidepressant.

lamictal+antidepressant.

lamictal+upper

tca...sometimes. tca+lithium, tca+benzodiazepine, tca+'atypical,' now and then tca+upper, but that can cause cardio issues.

ssri or ssnri + buspirone...

ssri+wellbutrin...

ssnri+remeron

wellbutrin+remeron

mirapex is apparently an option, sometimes...but it seems not as monotherapy. looks more like...

ssri+mirapex; 'atypical' + mirapex; lamcital+mirapex+antidepressant

provigil or nuvigil in place of amphetamine or ritalin. now and then, wellbutrin+upper or provigil.

gabapentin, sometimes lyrica instead of a benzodiazepine.

 

Re: What do TRD patients take without an MAIO PCB

Posted by beckett2 on November 11, 2019, at 1:43:13

In reply to What do TRD patients take without an MAIO, posted by PCB on November 10, 2019, at 18:06:06

> Hey Everyone,
>
> Still plodding my way to find an alternative to nardil. Many psychiatrist do not prescribe MAOIs. Less then 1% of the prescribed antidepressants in the US are MAOIs.
>
> So most likely a majority of treatment resistant patients are never are offered Nardil, Parnate. Do think they end up on ECT, TMS? How can so many of us only respond to MAOIs, yet they are rarely prescribed?
>
> PCB

Yeah, like C_e said, a cocktail. TCA's maybe. That's what I've done. Have you been taking Nardil?

 

Re: What do TRD patients take without an MAIO PCB

Posted by pedr on November 18, 2019, at 11:07:01

In reply to What do TRD patients take without an MAIO, posted by PCB on November 10, 2019, at 18:06:06

> Hey Everyone,
>
> Still plodding my way to find an alternative to nardil. Many psychiatrist do not prescribe MAOIs. Less then 1% of the prescribed antidepressants in the US are MAOIs.
>
> So most likely a majority of treatment resistant patients are never are offered Nardil, Parnate. Do think they end up on ECT, TMS? How can so many of us only respond to MAOIs, yet they are rarely prescribed?
>
> PCB

Hey PCB,

so I'm 25+ years severe TRD and TR OCD (and other stuff). I've tried north of 80 medications, both alone and mostly in combo. I once felt actually good on Nardil+Ritalin but the PDoc got cold feet and stopped prescribing the Ritalin and back down I went. ECT, dTMS (42 sessions...) had no effect at all.

My current regimen is (in mg) 40 Fetzima, 30 Lexapro, 30 Ritalin, 60 Adderall, 2.5 Abilify, 45 Buspar, 300 Lyrica, 150 Trazodone, 40 Percocet (for Chronic Pain).

The key meds are Ritalin (obtained "illegally"), Adderall and Percocet. When I take a Percocet and an Adderall dose, I feel mostly human, from feeling totally worthless, empty and a "bad person".

I do not know why - and nor does my excellent PDoc - why this is.

The other meds basically act like a "base" to stabilise me, upon which the stims can firmly plant themselves.

Anyway, the TRD team at Mount Sinai, NYC want me to do Ketamine therapy. When that fails I can do VNS or DBS, which I'm slightly optimistic about as the stats are quite good for them.

Anyway, I hope this helps in some way.
Pete

 

Re: What do TRD patients take without an MAIO

Posted by linkadge on November 23, 2019, at 7:58:42

In reply to Re: What do TRD patients take without an MAIO PCB, posted by pedr on November 18, 2019, at 11:07:01

Selegiline (more selective for MAOB) can be combined with SSRIs (although some doctors may be reluctant to combine).

A worthy trial might be say selegiline + sertraline.

Linkadge

 

Re: What do TRD patients take without an MAIO

Posted by undopaminergic on November 29, 2019, at 11:31:25

In reply to Re: What do TRD patients take without an MAIO, posted by linkadge on November 23, 2019, at 7:58:42

> Selegiline (more selective for MAOB) can be combined with SSRIs (although some doctors may be reluctant to combine).
>
> A worthy trial might be say selegiline + sertraline.
>
> Linkadge

Caution is advised with that combination. I have tried it myself, so yes, it is possible, but it produces serotonin toxicity in a subset of cases.

I might suggest trying TCAs if you haven't. You may combine with a stimulant such as methylphenidate or modafinil if you need a dopaminergic effect.

Cheers,
undopaminergic

 

Re: What do TRD patients take without an MAIO undopaminergic

Posted by linkadge on November 30, 2019, at 7:29:07

In reply to Re: What do TRD patients take without an MAIO, posted by undopaminergic on November 29, 2019, at 11:31:25

With lower doses, you'd be more selectively inhibiting MAO-B. But yes, in theory it could cause serotonin syndrome.

The effect of monoamine oxidase inhibitors can not easily be replicated by monoamine reuptake inhibitors. MAOIs break down a number of trace amines, which likely contributes to their unique properties.

Linkadge

 

Re: What do TRD patients take without an MAIO linkadge

Posted by undopaminergic on December 2, 2019, at 7:10:08

In reply to Re: What do TRD patients take without an MAIO undopaminergic, posted by linkadge on November 30, 2019, at 7:29:07

> With lower doses, you'd be more selectively inhibiting MAO-B. But yes, in theory it could cause serotonin syndrome.
>

Yes, the selectivity is dose dependent. However, this is complicated by the fact that the same dose can have different effects in different people. It also depends on the dose of the serotonergic agent, and the level of serotonin reuptake inhibiton it produces.

> The effect of monoamine oxidase inhibitors can not easily be replicated by monoamine reuptake inhibitors.
>

Agreed.

> [MAOs] break down a number of trace amines, which likely contributes to their unique properties.
>

Yes, some authors have even suggested that MAO-B may be appropriately called "phenylethylaminase". Even so, it did not seem to work for me, and even augmentation with phenylalanine did not produce any noticeable effects for me. I had to take phenylethylamine itself, and that was a powerful intervention, which should be used with care; it is possible to achieve the same kind of adverse and neurotoxic effects as with amphetamines.

-undopaminergic

 

Re: What do TRD patients take without an MAIO linkadge

Posted by undopaminergic on December 2, 2019, at 7:10:21

In reply to Re: What do TRD patients take without an MAIO undopaminergic, posted by linkadge on November 30, 2019, at 7:29:07

> With lower doses, you'd be more selectively inhibiting MAO-B. But yes, in theory it could cause serotonin syndrome.
>

Yes, the selectivity is dose dependent. However, this is complicated by the fact that the same dose can have different effects in different people. It also depends on the dose of the serotonergic agent, and the level of serotonin reuptake inhibiton it produces.

> The effect of monoamine oxidase inhibitors can not easily be replicated by monoamine reuptake inhibitors.
>

Agreed.

> [MAOs] break down a number of trace amines, which likely contributes to their unique properties.
>

Yes, some authors have even suggested that MAO-B may be appropriately called "phenylethylaminase". Even so, it did not seem to work for me, and even augmentation with phenylalanine did not produce any noticeable effects for me. I had to take phenylethylamine itself, and that was a powerful intervention, which should be used with care; it is possible to achieve the same kind of adverse and neurotoxic effects as with amphetamines.

-undopaminergic

 

Re: What do TRD patients take without an MAIO undopaminergic

Posted by linkadge on December 2, 2019, at 9:11:20

In reply to Re: What do TRD patients take without an MAIO linkadge, posted by undopaminergic on December 2, 2019, at 7:10:08

Nice chat,

Amphetamines are not always neurotoxic. In lower dose paradigms (i.e. stroke rehabilitation) they can actually be neurotrophic. I remember reading a study that low dose meth actually enhanced synaptic plasticity and recovery after TBI.

I've never taken selegiline but I often do well by adding the herb FO-TI (purportedly fairly selective towards MAO-B) and it helps quite a bit with energy and focus.

Selegiline can have differential effects on MAOA vs. MAOB in different species (i.e. mice vs. primates). I haven't seen any studies of such variation in humans, but purportedly it can lose it's selectivity towards MAO-B over time, which could lead to interactions.

In my own experience with monoamine reuptake inhibitors and MAOIs, MAOIs produce a much different feel to them. For MAO-A, there are other trace amines (such as tryptamine) whose elevation may enhance the clinical effect as dose psychedelics may have antidepressant effects for some individuals.

Linkadge

 

Re: What do TRD patients take without an MAIO

Posted by linkadge on December 2, 2019, at 9:15:25

In reply to Re: What do TRD patients take without an MAIO linkadge, posted by undopaminergic on December 2, 2019, at 7:10:21

I have a bottle of PEA which I use periodically when nothing else works. I prefer it to an MAO-B inhibitor because of half life (much shorter and hence interferes less with sleep).

The problem is that most doctors just throw SSRIs at you and don't really listen to insights gathered through 'experimentation'.

I have issues with attention (either bipolar or ADHD). Interestingly PEA calms me down rather than revs me up. It also clears my head and allows me to concentrate (i.e. read for more than 5-10 min at a time).

Linkadge

 

Re: What do TRD patients take without an MAIO linkadge

Posted by pedr on December 2, 2019, at 10:07:39

In reply to Re: What do TRD patients take without an MAIO, posted by linkadge on December 2, 2019, at 9:15:25

Hi Linkadge,

I suffer from inattentive ADD - I can't read more than a sentence, I get disinterested very quickly and so on. I also have severe TRD (I just failed Ketamine therapy).

Anyway, can you post a link where I can buy PEA e.g. amazon?

I tried Nardil 3 times and Parnate once. I responded to Nardil only when a stimulant was added. That was wonderful whilst it lasted but then the PDoc got cold feet :( The other times on Nardil and the Parnate were horrific. I was incredibly depressed, even at very high doses.

Cheers, Pedr

> I have a bottle of PEA which I use periodically when nothing else works. I prefer it to an MAO-B inhibitor because of half life (much shorter and hence interferes less with sleep).
>
> The problem is that most doctors just throw SSRIs at you and don't really listen to insights gathered through 'experimentation'.
>
> I have issues with attention (either bipolar or ADHD). Interestingly PEA calms me down rather than revs me up. It also clears my head and allows me to concentrate (i.e. read for more than 5-10 min at a time).
>
> Linkadge

 

Re: What do TRD patients take without an MAIO linkadge

Posted by undopaminergic on December 4, 2019, at 9:07:46

In reply to Re: What do TRD patients take without an MAIO undopaminergic, posted by linkadge on December 2, 2019, at 9:11:20

> Nice chat,
>

Glad you like it, even though I'm not at my best.

> Amphetamines are not always neurotoxic.
>

No, it's dose related. There is a point at which elevated extracellular dopamine begins to produce oxidative stress. Eg. cocaine and even more potent dopamine reuptake inhibitors do not achieve toxic DA elevations. Amphetamines do have that power (again, provided the dose is high enough).

Many people with ADD/ADHD who take it as prescribed continue to enjoy therapeutic benefits in the long term.

> In lower dose paradigms (i.e. stroke rehabilitation) they can actually be neurotrophic. I remember reading a study that low dose meth actually enhanced synaptic plasticity and recovery after TBI.
>

Interesting. I didn't know.

> I've never taken selegiline but I often do well by adding the herb FO-TI (purportedly fairly selective towards MAO-B) and it helps quite a bit with energy and focus.
>

That's great that you have found something that helps.

> In my own experience with monoamine reuptake inhibitors and MAOIs, MAOIs produce a much different feel to them. For MAO-A, there are other trace amines (such as tryptamine) whose elevation may enhance the clinical effect as dose psychedelics may have antidepressant effects for some individuals.
>

I'd really like to try tranylcypromine, or failing that, isocarboxazide or EMSAM, but they aren't available where I live (Nordic countries).

You can safely add NRIs and DRIs to a MAOI. NRIs even counteract tyramine, because they reduce the uptake of tyramine (via the reuptake transporter) into sympathetic nerve terminals.

-undopaminergic

 

Re: What do TRD patients take without an MAIO linkadge

Posted by undopaminergic on December 4, 2019, at 9:19:32

In reply to Re: What do TRD patients take without an MAIO, posted by linkadge on December 2, 2019, at 9:15:25

> I have a bottle of PEA which I use periodically when nothing else works. I prefer it to an MAO-B inhibitor because of half life (much shorter and hence interferes less with sleep).
>

It's my understanding that PEA without MAO-B inhibition produces no effects, at a dose up to at least 1 gram. At least that's what Shulgin reports. I haven't tried PEA without selegiline, except via phenylalanine (which gets decarboxylated to PEA).

> The problem is that most doctors just throw SSRIs at you and don't really listen to insights gathered through 'experimentation'.
>

Sadly, that is very true.

> I have issues with attention (either bipolar or ADHD). Interestingly PEA calms me down rather than revs me up. It also clears my head and allows me to concentrate (i.e. read for more than 5-10 min at a time).
>

That is what amphetamines do in ADHD, often referred to as a "paradoxical calming effect".

I experienced it myself, with the first few doses of PEA.

-undopaminergic

 

Re: What do TRD patients take without an MAIO pedr

Posted by linkadge on December 6, 2019, at 18:07:55

In reply to Re: What do TRD patients take without an MAIO linkadge, posted by pedr on December 2, 2019, at 10:07:39

Hey,

Here is a link for PEA supplement on Amazon.com

https://www.amazon.com/Bulksupplements-Phenylethylamine-HCL-Powder-grams/dp/B00ENRRBYO/ref=redir_mobile_desktop?_encoding=UTF8&aaxitk=W6pvZ3CDljGiw9n3YJ7Z4w&hsa_cr_id=8644961440201

I live in Canada and they don't have it on Amazon.ca (not sure why). Anyhow, if you're in the US you shouldn't have a problem. If you're in Canada, you may need to search different Amazon vendors to find one that ships to Canada.

Linkadge

 

Re: What do TRD patients take without an MAIO undopaminergic

Posted by linkadge on December 6, 2019, at 18:15:25

In reply to Re: What do TRD patients take without an MAIO linkadge, posted by undopaminergic on December 4, 2019, at 9:07:46

Cocaine and amphetamine work in different ways to elevate dopamine levels. It may not be the elevation in dopamine levels (per se) that leads to neurotoxicity. Cocaine works as more of a monoamine reuptake inhibitor whereas amphetamine causes the transport to work in reverse (forcing more dopamine out of the presynaptic neuron).

Interestingly, cocaine (or Ritalin) can actually block the neurotoxic effects of amphetamines!. But, combining the two (can) produce a synergistic elevation in dopamine.

Also, dopamine agonists (like Mirapex) can be neuroprotective.

There may be something else going on with amphetamine because it has other targets (i.e. sigma receptors, and TAAR1 receptors). Sigma agonism (in a certain dose range) can be neurotrophic but at higher doses can be neurotoxic. The sigma actions of amphetamine may be more involved in the neurotoxicity than dopamine elevations.

Another interesting tidbit is that caffeine raises dopamine but is neuroprotective (and can prevent Parkinson like dopamine receptor decline).

But, I really don't know as I am not an expert.

Linkadge

 

Re: What do TRD patients take without an MAIO pedr

Posted by linkadge on December 6, 2019, at 18:17:06

In reply to Re: What do TRD patients take without an MAIO linkadge, posted by pedr on December 2, 2019, at 10:07:39

Hey PEDR,

If you do take PEA be VERY careful. It's effects can be highly variable and can (in combination with a MAOI) behave like higher dose amphetamine.

I recommend stating with a tiny measured amount mixed in water. Drink SMALL amounts and see what the effect is.

Linkadge

 

Re: What do TRD patients take without an MAIO undopaminergic

Posted by linkadge on December 6, 2019, at 18:21:59

In reply to Re: What do TRD patients take without an MAIO linkadge, posted by undopaminergic on December 4, 2019, at 9:19:32

From my standpoint it is not really accurate to say that PEA is inactive without an MAOI.

There are likely sizable variations in individual (functional) MAOB activity that can influence individual reactions to PEA.

I have a huge reaction to PEA (to the point that I need to dissolve a 90mg cap and take tiny sips).

Mind you, I do consume quite a bit of dark chocolate, coffee and green tea daily (both of which have some documented MAOI properties (stronger towards MAO-B in the case of chocolate and green tea).

Linkadge

 

Re: What do TRD patients take without an MAIO linkadge

Posted by pedr on December 6, 2019, at 18:25:06

In reply to Re: What do TRD patients take without an MAIO pedr, posted by linkadge on December 6, 2019, at 18:17:06

> Hey PEDR,
>
> If you do take PEA be VERY careful. It's effects can be highly variable and can (in combination with a MAOI) behave like higher dose amphetamine.
>
> I recommend stating with a tiny measured amount mixed in water. Drink SMALL amounts and see what the effect is.
>
> Linkadge
Dosing was actually going to be my next question - thank you. Pete

 

Re: What do TRD patients take without an MAIO linkadge

Posted by pedr on December 6, 2019, at 18:27:27

In reply to Re: What do TRD patients take without an MAIO undopaminergic, posted by linkadge on December 6, 2019, at 18:21:59

> From my standpoint it is not really accurate to say that PEA is inactive without an MAOI.
>
> There are likely sizable variations in individual (functional) MAOB activity that can influence individual reactions to PEA.
>
> I have a huge reaction to PEA (to the point that I need to dissolve a 90mg cap and take tiny sips).
>
> Mind you, I do consume quite a bit of dark chocolate, coffee and green tea daily (both of which have some documented MAOI properties (stronger towards MAO-B in the case of chocolate and green tea).
>
> Linkadge
>

I tried eating lots of dark chocolate and didn't respond.

W.r.t. Dosing, I've ended up in the ER (with my young kids...) because of misjudging a Vyvanse dose whilst on Nardil so I'll tread carefully. Cheers.

 

Re: What do TRD patients take without an MAIO pedr

Posted by linkadge on December 7, 2019, at 8:03:41

In reply to Re: What do TRD patients take without an MAIO linkadge, posted by pedr on December 6, 2019, at 18:27:27

Yeah, if you're taking Nardil, then PEA dosing would definitely need to be adjusted downwards. If you purchase in capsules, DO NOT take an entire capsule to start.

You can easily adjust upwards, but not so well downwards.

Linkadge


 

Re: What do TRD patients take without an MAIO linkadge

Posted by undopaminergic on December 9, 2019, at 9:14:33

In reply to Re: What do TRD patients take without an MAIO undopaminergic, posted by linkadge on December 6, 2019, at 18:15:25

> Cocaine and amphetamine work in different ways to elevate dopamine levels.
>

Of course. I hesitate to call myself an expert, because the more I learn, the more I realise there is so much more to learn, but at least relatively speaking, stimulants are one of my areas of expertise.

> It may not be the elevation in dopamine levels (per se) that leads to neurotoxicity.
>

No, it is not the elevated dopamine *itself* that is neurotoxic. Rather, it is the metabolism thereof, which leads to oxidative stress. But now, stumbling across this article:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870191/
I realise it is more complex than I had thought. See, that's what I meant when I said the more I learn, the more I realise how much more there is to learn.

> Cocaine works as more of a monoamine reuptake inhibitor ...
>

Of course. There may be less important actions as well, including modestly increased dopamine release. As a matter of fact, you called my attention to this in a debate many years ago!

> whereas amphetamine causes the transport to work in reverse (forcing more dopamine out of the presynaptic neuron).
>

Of course.

> Interestingly, cocaine (or Ritalin) can actually block the neurotoxic effects of amphetamines!.
>

Yes, it is interesting, but it follows from the fact that amphetamines need the DAT (dopamine transporter) in order to produce their effects, and cocaine inhibits that transporter.

> But, combining the two (can) produce a synergistic elevation in dopamine.
>

"can" is the keyword. This is complex, and I don't have a good understanding of it.

> Also, dopamine agonists (like Mirapex) can be neuroprotective.
>

Yes, but these agonists are not identical to dopamine; their metabolism does not produce oxidative stress. Indeed pramipexole (Sifrol; Mirapex?) has been show to have antioxidant properties.

> There may be something else going on with amphetamine because ...
>

Many things, it seems, including increased release of glutamate; see the article I referenced above.

> it has other targets (i.e. sigma receptors, and TAAR1 receptors). Sigma agonism (in a certain dose range) can be neurotrophic but at higher doses can be neurotoxic. The sigma actions of amphetamine may be more involved in the neurotoxicity than dopamine elevations.
>

I did not know amphetamines modulate sigma. Cocaine definitely does, and it is apparently associated with the seizures sometimes resulting from cocaine overdose. Although cocaine seems to be a more potent sigma-agonist (amph. do not produce seizures), it does not produce the same neurotoxicity as the amphetamines.

> Another interesting tidbit is that caffeine raises dopamine but is neuroprotective (and can prevent Parkinson like dopamine receptor decline).
>

Yes (I knew about the DA elevation but not the neuroprotection), and caffeine-like stimulants (primarily adenosine-receptor antagonists) have been researched as a treatment for Parkinson's.

I have personal (first-hand) experience with this. At some point, cocaine-like stimulants (in my case, ethylphenidate and desoxypipradrol) alone seemed to lose most of their effects, but when combined with ~ 500-1000 mg of caffeine, I get excellent effects. Severely nootropic!

> But, I really don't know as I am not an expert.
>

You are certainly one of the more well-informed people I've met regarding these issues.

-undopaminergic

 

Re: What do TRD patients take without an MAIO linkadge

Posted by undopaminergic on December 9, 2019, at 9:36:36

In reply to Re: What do TRD patients take without an MAIO undopaminergic, posted by linkadge on December 6, 2019, at 18:21:59

> From my standpoint it is not really accurate to say that PEA is inactive without an MAOI.
>

Apparently, you are right. However, given Shulgin's report, it seems typical that it is inactive.

> There are likely sizable variations in individual (functional) MAOB activity that can influence individual reactions to PEA.
>

Apparently. It would be interesting to study this further. People like you, who are highly sensitive to PEA, must have differing neurology than those who experience no effect.

> I have a huge reaction to PEA (to the point that I need to dissolve a 90mg cap and take tiny sips).
>

It's nice to hear you've found a (legal) stimulant that works for you.

> Mind you, I do consume quite a bit of dark chocolate, coffee and green tea daily (both of which have some documented MAOI properties (stronger towards MAO-B in the case of chocolate and green tea).
>

I didn't know these substances had MAOI properties. I did know, however, that cocoa is particularly high in PEA content. It is sometimes called the "chocolate amphetamine".

-undopaminergic

 

Re: What do TRD patients take without an MAIO

Posted by linkadge on December 9, 2019, at 17:15:19

In reply to Re: What do TRD patients take without an MAIO linkadge, posted by undopaminergic on December 9, 2019, at 9:14:33

>No, it is not the elevated dopamine *itself* that >is neurotoxic. Rather, it is the metabolism >thereof, which leads to oxidative stress. But now, >stumbling across this article:

Right. There is the possibility of amphetamine (and related substances) as being directly neurotoxic (in a manner that substances like MTPP are). Anything that leads to excessive glutamate function, in theory can be neurotoxic.

However, I've never heard of cocaine blocking the high associated with amphetamine (although I only know a few people personally that would have mixed the two), even though, it appears it can block the neurotoxicity. I would imagine, however, that cocaine would lead to increased glutamate levels (at least in some brain regions).

>Yes, it is interesting, but it follows from the >fact that amphetamines need the DAT (dopamine >transporter) in order to produce their effects, >and cocaine inhibits that transporter.

I don't know if cocaine only blocks the transporter within the synaptic junction, or whether it also enters the presynaptic neuron and prevents the dopamine transporter function there. Complicating the picture is the action of the presynaptic dopamine autoreceptor system. Cocaine can actually calm hyperactive mice in a similar fashion to Ritalin. This may be via stimulation of dopamine autoreceptors. Amphetamine too may lower dopamine release (in ADHD) via TAAR1's interaction with presynaptic dopamine autoreceptors. TAAR1 agonsits actually reduce dopamine release. Hence the anti-hyperkinetic effects of amphetamines may have nothing to do with their direct actions on the dopamine transporter.

>Yes, but these agonists are not identical to >dopamine; their metabolism does not produce >oxidative stress. Indeed pramipexole (Sifrol; >Mirapex?) has been show to have antioxidant >properties.

True, and it may depend on the degree (and location) of dopaminergic stimulation. Caffiene, adenosine antagonists, and MAO-B inhibitors are typically neuroprotective but they increase dopamine to a lesser degree than amphetamine.

I don't know the relative potency of amphetamines vs. cocaine for sigma receptors, and there are two subtypes of sigma receptors that have different effects. Some sigma agonsits are neuroprotective (sigma-1?) and others have more neurotoxic effects. The neurotrophic effects (and cognitive enhancing effects of amphetamines) may be via sigma-1 receptors. There is an increased propensity for schizohprenics to use amphetamines. I have wondered if the TAAR1 agonism and sigma-1 agonism (which have antipsychotic qualities in some paradigms) may control certain psychotic symptoms (in a certain dose range). Wikipedia lists meth as a sigma agonist, but I believe I have seen this property for amphetamines as well.

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

Amphetamines have other targets (like inhibition of MAO-A) which may exert some anticonvulsant effect. Fenfluramine (amphetamine derivative) has anticonvulsant effects (which may be related to 5-ht2c agonism). It has been used with some success for Dravet syndrome. I believe amphetamines can interact with 5-ht2c as well, which might mediate with anorexigenic and anticonvulsant properties. Or, as you mention, sigma receptors could be involved.

What were we originally talking about :)

Linkadge


 

Re: What do TRD patients take without an MAIO

Posted by linkadge on December 9, 2019, at 17:26:32

In reply to Re: What do TRD patients take without an MAIO linkadge, posted by undopaminergic on December 9, 2019, at 9:36:36

The catechins in cocoa are MAO inhibitors (more selective to MAO-B). They also have some monoamine reuptake effects (more selective for norepinephrine). I've felt that the combination of a MAO-B inhibitor and a NET inhibitor would be particularly good for cognitive problems.

I'm not sure what degree of MAO-B inhibition one would get through regular chocolate consumption, but polyphenols like catechin can build up in the system over time.

Cocoa (and coffee) also contain beta carbolines which are MAOIs (more selective towards MAO-A). The beta carbolines are also benzodiazepine antagonists (can increase anxiety). I believe the beta carbolines were originally identified as the first endogenous benzodiazepine antagonists. There is another endogenous compound called isatin which is both a MAOI and a benzodiazepine receptor antagonist. It is released during stress (I presume to give a quick fight / flight response).

If you gave me 10-20 mg of PEA in a capsule and an identical placebo, I could identify the PEA 100% of the time. The problem is that the effects are fairly short lasting. However, if I use the energy boost to get exercising, it can help improve mood for a longer duration.

Linkadge


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