Psycho-Babble Medication Thread 494113

Shown: posts 1 to 17 of 17. This is the beginning of the thread.

 

Reuptake Inhibitors and MAO decrease?

Posted by cache-monkey on May 5, 2005, at 13:33:31

Up the board a ways, Elroy wrote the following about SSRIs: << The problem with this approach is that these drugs DO NOT increase serotonin levels and in fact deplete reserves of the [neurotransmitter]. This occurs because the SSRI class drugs cause an increase in an enzyme called MAO It is common for people to experience only temporary improvement due to this effect. >>

I'm wondering whether there's any truth to this statement. E.g. have there been any studies showing this link?

Maybe I'm just paranoid, but I feel like my one experience with reuptake inhibitors (Wellbutrin + Celexa) left me worse off after withdrawing.

Would the converse of this be that MAOIs increase stores and production of neurotransmitters? Is that maybe why MAOIs work better for refractory and recurrent depression?

Input greatly appreciated,
cache-monkey

 

Re: Reuptake Inhibitors and MAO decrease?

Posted by SLS on May 5, 2005, at 18:33:46

In reply to Reuptake Inhibitors and MAO decrease?, posted by cache-monkey on May 5, 2005, at 13:33:31

> Up the board a ways, Elroy wrote the following about SSRIs: << The problem with this approach is that these drugs DO NOT increase serotonin levels and in fact deplete reserves of the [neurotransmitter]. This occurs because the SSRI class drugs cause an increase in an enzyme called MAO It is common for people to experience only temporary improvement due to this effect. >>

I've never heard of this. That doesn't mean that there doesn't exist written material about it, though. My knee-jerk reaction is to say that the magnitude of reuptake inhibition outweighs any increase in MAO activity that an SSRI might produce.


- Scott

 

Re: Reuptake Inhibitors and MAO decrease? cache-monkey

Posted by Chairman_MAO on May 5, 2005, at 20:16:57

In reply to Reuptake Inhibitors and MAO decrease?, posted by cache-monkey on May 5, 2005, at 13:33:31

My own knee-jerk reaction is that it's B.S. If there really were that much serotonin being released as to outstrip the capacity of MAO to break it down, you'd have people having serotonin syndrome all over the place, interactions with sudafed, etc. I'm not saying that it cannot happen or doesn't happen, but I'd like to see real evidence here.

 

Re: Reuptake Inhibitors and MAO decrease? SLS

Posted by cache-monkey on May 6, 2005, at 1:02:37

In reply to Re: Reuptake Inhibitors and MAO decrease?, posted by SLS on May 5, 2005, at 18:33:46

Hi Scott,

Well, I guess I'm wondering about what happens when discontinuing an SSRI. MAO might have adjusted upward a little bit. Removing the reuptake inhibitor might leave you worse off for a time until MAO adjusts back down. I could imagine a class of people who are slow to adjust and so get rebound depression.

Pure speculation on my part, though. (And a convenient way to explain my mental health progression.)

~cache-monkey

> > Up the board a ways, Elroy wrote the following about SSRIs: << The problem with this approach is that these drugs DO NOT increase serotonin levels and in fact deplete reserves of the [neurotransmitter]. This occurs because the SSRI class drugs cause an increase in an enzyme called MAO It is common for people to experience only temporary improvement due to this effect. >>
>
> I've never heard of this. That doesn't mean that there doesn't exist written material about it, though. My knee-jerk reaction is to say that the magnitude of reuptake inhibition outweighs any increase in MAO activity that an SSRI might produce.
>
>
> - Scott

 

Re: Reuptake Inhibitors and MAO *increase*?

Posted by cache-monkey on May 6, 2005, at 1:04:28

In reply to Reuptake Inhibitors and MAO decrease?, posted by cache-monkey on May 5, 2005, at 13:33:31

Oops, what I meant to say was increase... i.e. MAO goes up in the presence of an uptake inhibitor.

> Up the board a ways, Elroy wrote the following about SSRIs: << The problem with this approach is that these drugs DO NOT increase serotonin levels and in fact deplete reserves of the [neurotransmitter]. This occurs because the SSRI class drugs cause an increase in an enzyme called MAO It is common for people to experience only temporary improvement due to this effect. >>
>
> I'm wondering whether there's any truth to this statement. E.g. have there been any studies showing this link?
>
> Maybe I'm just paranoid, but I feel like my one experience with reuptake inhibitors (Wellbutrin + Celexa) left me worse off after withdrawing.
>
> Would the converse of this be that MAOIs increase stores and production of neurotransmitters? Is that maybe why MAOIs work better for refractory and recurrent depression?
>
> Input greatly appreciated,
> cache-monkey

 

Re: Reuptake Inhibitors and MAO increase? Chairman_MAO

Posted by cache-monkey on May 6, 2005, at 1:09:47

In reply to Re: Reuptake Inhibitors and MAO decrease? cache-monkey, posted by Chairman_MAO on May 5, 2005, at 20:16:57

My subject line was wrong. I meant to say MAO could increase after exposure to an SSRI. It's definitely speculative, but see my response to Scott.

> My own knee-jerk reaction is that it's B.S. If there really were that much serotonin being released as to outstrip the capacity of MAO to break it down, you'd have people having serotonin syndrome all over the place, interactions with sudafed, etc. I'm not saying that it cannot happen or doesn't happen, but I'd like to see real evidence here.

 

Mode of action unknown

Posted by Wee Willy on May 6, 2005, at 1:49:58

In reply to Re: Reuptake Inhibitors and MAO increase? Chairman_MAO, posted by cache-monkey on May 6, 2005, at 1:09:47

I know everyone has heard this and I guess it goes in one ear and out the other. Absolutely possitively it is not understood how these chemicals do what they do. We seem to have a irressitable need to know what is the process that is occuring within us. That answer is not here yet. Monominergic theories have lost ground from their hayday, why beat a dead horse?

 

Re: Mode of action unknown Wee Willy

Posted by Chairman_MAO on May 6, 2005, at 8:37:54

In reply to Mode of action unknown, posted by Wee Willy on May 6, 2005, at 1:49:58

They've more than lost ground, they're effectively dead in the incarnation that people generally refer to when they refer to "chemical imbalance", etc. A "low serotonin level" is simply not what is going on; moreover, the entire concept is incoherent. I am skeptical of any explanation that people have re: psychoactive drug action insofar as it relates to behavior or thought because our neuroscience--and, if I may say so, our physics--would need to be radically revised in order to develop any account of the mind-brain link that passes any philosophical muster.

However, even if we're talking strictly about the objective here, the classical monoaminergic theories are bunk according to today's neuroscience.

 

Re: Mode of action unknown Chairman_MAO

Posted by Bob on May 7, 2005, at 13:48:24

In reply to Re: Mode of action unknown Wee Willy, posted by Chairman_MAO on May 6, 2005, at 8:37:54


> However, even if we're talking strictly about the objective here, the classical monoaminergic theories are bunk according to today's neuroscience.

If all the monoaminergic theories are bunk, then is there any sort of guesses out there, or what?

Are MAOI's considered any better, in general, then other classes of drugs?

My psychiatrist told me a couple weeks ago that there is a new theory floating around about how antidepressants only help for a little while in many people, and then peter out. The new theory is that possibly it is better to treat with a mild amount of mood stabilizer, and let the brain try to balance it's chemistry on its own. Of course, this begs all kinds of questions, like what happens when people are in a serious crisis, or have intractable anxiety, or whatever.

 

Re: Mode of action unknown Bob

Posted by Chairman_MAO on May 8, 2005, at 12:28:18

In reply to Re: Mode of action unknown Chairman_MAO, posted by Bob on May 7, 2005, at 13:48:24

The new theories concerning many types of DEPRESSION involve neurosteroids, second messenger systems/G-protein coupled receptors, etc. Of course fiddling with the monoamines can produce many effects, and of course they're intimately involved in mood, cognition, etc, but the theories that appeal to simple "chemical imbalances" and "neurotransmitter deficiencies" are utterly out of date.

Anxiety is a different story, although that also is mediated not just monoaminergically, but GABAnergically, by CCK, neurosteroids (allopregnanolone), etc. What I believe is that consciousness is the sum total of all neural activity (a la Daniel Dennett's "multiple drafts model"), and so to isolate any one neurotransmitter system/subsystem and say that it is responsible for something as complex as depression is absurd.

I believe MAOIs work better for many people because they act in a fundamentally different way than reuptake inhibitors, etc. That is, they alter the catabolism of neurotransmitters, and it is that simple alteration that produces a cascade of events while the brain attempts to restore homeostasis. It is the newfound homeostasis built around the elevated levels of monoamines (and GABA, with phenelzine) that produces the antidepressant/anxiolytic effect. You may say, "Hey, but reuptake inhibitors are doing the same thing, just by a different mechanism" Well, that is partially correct, however MAO is present INSIDE neurons themselves, and so--if I am correct here--taking an MAOI can actually alter the amount of neurotransmitter stored INSIDE a given neuron. Anyone that's taken a drug (such as cocaine) or a combination of drugs that blocks the reuptake of all three monoamines and also has taken an MAOI knows that the qualitative effect of the drugs are vastly different. There are many reasons for this, most, I believe, we are not capable of elucidating given the current state of the science. I know when I took Effexor + amphetamine and Effexor + Ritalin, or lexapro + selegiline, the effects were absolutely nothing like Nardil or Parnate in any way.

 

Re: Mode of action unknown Chairman_MAO

Posted by Larry Hoover on May 8, 2005, at 12:57:24

In reply to Re: Mode of action unknown Bob, posted by Chairman_MAO on May 8, 2005, at 12:28:18

> Well, that is partially correct, however MAO is present INSIDE neurons themselves, and so--if I am correct here--taking an MAOI can actually alter the amount of neurotransmitter stored INSIDE a given neuron.

I'm just skimming this thread, and this jumped out.....

I believe MAO is a synaptic cleft enzyme, designed to "corral" any stray neurotransmitter that didn't: a) hit its designated receptor (post-synaptic); b) hit its designated auto-receptor (pre-synaptic); c) get vacuumed up by the reuptake pump (pre-synaptic). Inhibiting MAO would, presumably, slightly enhance all of the above. However, it shunts "escaped" neurotransmitters to other scavenger enzymes, e.g. COMT. Thus, the metabolites of the catecholamines must change proportion and concentration. Perhaps that is the mode of action, metabolite-mediated response elements.

Lar

 

Re: Mode of action unknown Chairman_MAO

Posted by Bob on May 8, 2005, at 13:13:45

In reply to Re: Mode of action unknown Bob, posted by Chairman_MAO on May 8, 2005, at 12:28:18

> The new theories concerning many types of DEPRESSION involve neurosteroids, second messenger systems/G-protein coupled receptors, etc. Of course fiddling with the monoamines can produce many effects, and of course they're intimately involved in mood, cognition, etc, but the theories that appeal to simple "chemical imbalances" and "neurotransmitter deficiencies" are utterly out of date.
>
> Anxiety is a different story, although that also is mediated not just monoaminergically, but GABAnergically, by CCK, neurosteroids (allopregnanolone), etc. What I believe is that consciousness is the sum total of all neural activity (a la Daniel Dennett's "multiple drafts model"), and so to isolate any one neurotransmitter system/subsystem and say that it is responsible for something as complex as depression is absurd.
>
> I believe MAOIs work better for many people because they act in a fundamentally different way than reuptake inhibitors, etc. That is, they alter the catabolism of neurotransmitters, and it is that simple alteration that produces a cascade of events while the brain attempts to restore homeostasis. It is the newfound homeostasis built around the elevated levels of monoamines (and GABA, with phenelzine) that produces the antidepressant/anxiolytic effect. You may say, "Hey, but reuptake inhibitors are doing the same thing, just by a different mechanism" Well, that is partially correct, however MAO is present INSIDE neurons themselves, and so--if I am correct here--taking an MAOI can actually alter the amount of neurotransmitter stored INSIDE a given neuron. Anyone that's taken a drug (such as cocaine) or a combination of drugs that blocks the reuptake of all three monoamines and also has taken an MAOI knows that the qualitative effect of the drugs are vastly different. There are many reasons for this, most, I believe, we are not capable of elucidating given the current state of the science. I know when I took Effexor + amphetamine and Effexor + Ritalin, or lexapro + selegiline, the effects were absolutely nothing like Nardil or Parnate in any way.

So, Larry, am I to gather that you are taking an MAOI, and that it is helping you? If you have taken one in the past and have now discontinued it, I'd like to ask why.

BTW, your theory explanation is a little bit of a downer to me, as what I get from it is we are decades, and possibly centuries away from being able to reliably help people.

 

Re: Mode of action unknown Chairman_MAO

Posted by Bob on May 8, 2005, at 13:25:16

In reply to Re: Mode of action unknown Bob, posted by Chairman_MAO on May 8, 2005, at 12:28:18

Aren't tricyclics uniquely different in their method of action as well? Why would MAOI's be so much better than tricyclics?

 

Re: Mode of action unknown Chairman_MAO

Posted by ed_uk on May 8, 2005, at 15:10:39

In reply to Re: Mode of action unknown Bob, posted by Chairman_MAO on May 8, 2005, at 12:28:18

Hi,

I think you said you were at University. Are you doing a degree in pharmacology?

Ed.

 

Re: Mode of action unknown / MAO Larry Hoover

Posted by Chairman_MAO on May 8, 2005, at 18:56:54

In reply to Re: Mode of action unknown Chairman_MAO, posted by Larry Hoover on May 8, 2005, at 12:57:24


> I believe MAO is a synaptic cleft enzyme, designed to "corral" any stray neurotransmitter that didn't: a) hit its designated receptor (post-synaptic); b) hit its designated auto-receptor (pre-synaptic); c) get vacuumed up by the reuptake pump (pre-synaptic). Inhibiting MAO would, presumably, slightly enhance all of the above. However, it shunts "escaped" neurotransmitters to other scavenger enzymes, e.g. COMT. Thus, the metabolites of the catecholamines must change proportion and concentration. Perhaps that is the mode of action, metabolite-mediated response elements.
>
> Lar


http://www.cnsforum.com/imagebank/item/Drug_MOAI_2/index.html

Note how MAO-A is found intraneuronally as well. Thus MAOIs alter the amount of neurotransmitter available for release. One possible therapeutic mechanism I can postulate a priori is that certain people have disorders that perturb the storage of neurotransmitters inside neurons. MAOIs could allow proper amounts of the transmitter to accumulate. I don't know if this has ever been discussed in the literature or not--or if it even makes total sense, heh--just came to mind.

Contrarily, while MAO-A is found in synapses as well as intraneuronally in catacholaminergic neurons, MAO-B is primarily a glial enzyme and is also found in serotonergic neurons.

 

Re: Mode of action unknown / MAO Chairman_MAO

Posted by Larry Hoover on May 9, 2005, at 9:59:45

In reply to Re: Mode of action unknown / MAO Larry Hoover, posted by Chairman_MAO on May 8, 2005, at 18:56:54

>
> > I believe MAO is a synaptic cleft enzyme, designed to "corral" any stray neurotransmitter that didn't: a) hit its designated receptor (post-synaptic); b) hit its designated auto-receptor (pre-synaptic); c) get vacuumed up by the reuptake pump (pre-synaptic). Inhibiting MAO would, presumably, slightly enhance all of the above. However, it shunts "escaped" neurotransmitters to other scavenger enzymes, e.g. COMT. Thus, the metabolites of the catecholamines must change proportion and concentration. Perhaps that is the mode of action, metabolite-mediated response elements.
> >
> > Lar
>
>
> http://www.cnsforum.com/imagebank/item/Drug_MOAI_2/index.html
>
> Note how MAO-A is found intraneuronally as well. Thus MAOIs alter the amount of neurotransmitter available for release. One possible therapeutic mechanism I can postulate a priori is that certain people have disorders that perturb the storage of neurotransmitters inside neurons. MAOIs could allow proper amounts of the transmitter to accumulate. I don't know if this has ever been discussed in the literature or not--or if it even makes total sense, heh--just came to mind.

Thanks for expanding my knowledge. I just checked my mid-90's textbooks, and there is no mention of intraneuronal MAO.....only iterneuronal.

Note, in the diagram, though.....COMT is also intraneuronal. When you have two concurrent but divergent paths, and you inhibit one, you shunt to the other. I still think the COMT metabolites go on to trigger response elements, which lead to transduction via DNA/RNA/protein synthesis....i.e. gene regulation.

> Contrarily, while MAO-A is found in synapses as well as intraneuronally in catacholaminergic neurons, MAO-B is primarily a glial enzyme and is also found in serotonergic neurons.

Yes, that is now considered to be the primary active site of e.g. selegiline....the glia. We still don't know much about what the glia do. A decade ago, they were thought of as support cells, ones without regulatory activity. We now know that they are primary regulatory sites, initiating cascades of modulatory action.

Although fascinating to ponder, I must return to my critical thinking perspective......in the end, this is all what my favourite professor used to call hand-waving. "I know! I know!" <hands waving in the air>

We don't know, unfortunately.

Lar

 

Re: Mode of action unknown / MAO Larry Hoover

Posted by Chairman_MAO on May 11, 2005, at 20:30:21

In reply to Re: Mode of action unknown / MAO Chairman_MAO, posted by Larry Hoover on May 9, 2005, at 9:59:45

Yeah, I dig it. I think you're referring to what philosophers also like to call a "virtus dormitiva" explanation. That term originates supposedly from a professor hundreds of years ago who, when asked by a student why morphine induces sleep, explains that it is due to morphine's "virtus dormitiva" that it is sedating.

Virtus dormitiva, of course, means "sleep-inducing property". The best neuroscience currently can do--and it never does this one hundred percent--is tell us whether a given neuron or neurons will or will not fire. This has nothing to do with consciousness whatsoever, and so in a sense, the closer we get to a neurological explanation, the farther away we get from what we are trying to treat, which is in consciousness.

Aah, philosophy of mind, my sweet, sweet paramour! ;)


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