Psycho-Babble Medication Thread 1117157

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Ritalin + an MAOi = Greater baseline D/NE?

Posted by PeterMartin on October 5, 2021, at 0:35:16

I take Marplan (MAOi) and have recently added Ritalin again. I don't have any interactions between the 2, so I take a relatively "normal" dose of Ritalin IR at 40mg per day.

I know Ritalin (methylphenidate) works by increasing Norepinephrine and Dopamine in the brain, but it also has a short half-life of ~3hrs. Most people take it a few times a day, or an extended release variety to keep the effects.

My question is, being on an MAOi will taking Ritalin raise my baseline levels of Norepinephrine & dopamine over time, where it wouldn't in people who don't have their MAO inhibited?

I guess I'm wondering if it'd have more of an effect on me over time compared to other people.

I did take it along w/ Nardil & Marplan a while back for a couple of years, but I never really knew if it helped my mood aside from the immediate effects.

Thanks for any insight/discussion.

 

Re: Ritalin + an MAOi = Greater baseline D/NE?

Posted by undopaminergic on October 5, 2021, at 7:28:07

In reply to Ritalin + an MAOi = Greater baseline D/NE?, posted by PeterMartin on October 5, 2021, at 0:35:16

>
> My question is, being on an MAOi will taking Ritalin raise my baseline levels of Norepinephrine & dopamine over time, where it wouldn't in people who don't have their MAO inhibited?
>
> I guess I'm wondering if it'd have more of an effect on me over time compared to other people.
>
> I did take it along w/ Nardil & Marplan a while back for a couple of years, but I never really knew if it helped my mood aside from the immediate effects.
>

I've found that sometimes, I get withdrawal symptoms when I quit a stimulant I've been taking chronically. Mostly it is tiredness (I sleep more). On the other hand, however, sometimes chronic stimulant treatment gets me "in tune", so to speak, and I stay "in tune" for some time after quitting the stimulant.

-undopaminergic

 

Re: Ritalin + an MAOi = Greater baseline D/NE?

Posted by PeterMartin on October 5, 2021, at 11:31:19

In reply to Re: Ritalin + an MAOi = Greater baseline D/NE?, posted by undopaminergic on October 5, 2021, at 7:28:07


> I've found that sometimes, I get withdrawal symptoms when I quit a stimulant I've been taking chronically. Mostly it is tiredness (I sleep more). On the other hand, however, sometimes chronic stimulant treatment gets me "in tune", so to speak, and I stay "in tune" for some time after quitting the stimulant.
>
> -undopaminergic
>

Oh, I definitely get withdrawl....even if I try to skip a day. I'm kinda just curious if while I'm taking it there'll be an incremental effect along w/ the immediate acute burst of NE/DA.

 

Re: Ritalin + an MAOi = Greater baseline D/NE?

Posted by linkadge on October 5, 2021, at 19:34:28

In reply to Re: Ritalin + an MAOi = Greater baseline D/NE?, posted by undopaminergic on October 5, 2021, at 7:28:07

Taking a MAOI with ritalin will likely increase NE/DA signalling (beyond that of an MAOI alone), but I don't know if it will result in chronically elevated NE/DA (i.e. beyond the effect of the drug itself).

Studies in rats suggest that the 'stereotypy' induced by higher dose ritalin is increased by MAOIs (suggesting additive increased DA signalling). The irreversible MAOIs will result in longer term elevations in NE / DA, but I don't know if ritalin will result in persistent elevations in DA beyond the effect of the drug itself. My guess is no. Ritalin can upregulate the DA transporters over time, and so when the drug wears off, dopamine levels probably drop beyond baseline (i.e. the crash) for a period of time. That being said I have heard positive reviews from the combination.

Linkadge

 

Re: Ritalin + an MAOi = Greater baseline D/NE?

Posted by PeterMartin on October 6, 2021, at 14:10:53

In reply to Re: Ritalin + an MAOi = Greater baseline D/NE?, posted by linkadge on October 5, 2021, at 19:34:28

> Taking a MAOI with ritalin will likely increase NE/DA signalling (beyond that of an MAOI alone), but I don't know if it will result in chronically elevated NE/DA (i.e. beyond the effect of the drug itself).
>
> Studies in rats suggest that the 'stereotypy' induced by higher dose ritalin is increased by MAOIs (suggesting additive increased DA signalling). The irreversible MAOIs will result in longer term elevations in NE / DA, but I don't know if ritalin will result in persistent elevations in DA beyond the effect of the drug itself. My guess is no. Ritalin can upregulate the DA transporters over time, and so when the drug wears off, dopamine levels probably drop beyond baseline (i.e. the crash) for a period of time. That being said I have heard positive reviews from the combination.
>
> Linkadge

Always appreciate your insight Linkadge! Thanks!!

 

Re: Ritalin + an MAOi = Greater baseline D/NE? » PeterMartin

Posted by linkadge on October 8, 2021, at 15:49:26

In reply to Re: Ritalin + an MAOi = Greater baseline D/NE?, posted by PeterMartin on October 6, 2021, at 14:10:53

Of course, I don't know for sure. Sometimes strange things happen when multiple pathways of neurotransmitter are inhibited. For example, in some animal models of DAT + COMT + MAO inhibition, dopamine levels are significantly reduced vs. normal animals. Some of this is likely the result of early life modifications in neurotransmission. Also, there are the autoreceptors which slow monoamine firing when synaptic levels become too elevated.

Linkadge

 

Re: Ritalin + an MAOi = Greater baseline D/NE?

Posted by undopaminergic on October 11, 2021, at 9:45:01

In reply to Re: Ritalin + an MAOi = Greater baseline D/NE? » PeterMartin, posted by linkadge on October 8, 2021, at 15:49:26

> Of course, I don't know for sure. Sometimes strange things happen when multiple pathways of neurotransmitter are inhibited. For example, in some animal models of DAT + COMT + MAO inhibition, dopamine levels are significantly reduced vs. normal animals.
>

Are these gene knockouts or are the inhibitions produced in normal animals through drugs?

> Some of this is likely the result of early life modifications in neurotransmission. Also, there are the autoreceptors which slow monoamine firing when synaptic levels become too elevated.
>

This can be counteracted with sulpiride or its workalikes.

-undopaminergic

 

Re: Ritalin + an MAOi = Greater baseline D/NE? » undopaminergic

Posted by linkadge on October 15, 2021, at 21:07:00

In reply to Re: Ritalin + an MAOi = Greater baseline D/NE?, posted by undopaminergic on October 11, 2021, at 9:45:01

These are mice with double or triple gene knockouts.

The problem is that the reuptake process is also needed for the recycling of the neurotransmitter. So blocking reuptake does cause activation of the inhibitory autoreceptors slowing firing, but also blocking the resorption of the neurotransmitter for subsequent re-release.

Many reuptake inhibitors do more to 'stabilize' monoamine activity than really enhance it. The exception is the stimulants with a more complex mode of action.

Linkadge

 

Re: Ritalin + an MAOi = Greater baseline D/NE? » linkadge

Posted by undopaminergic on October 17, 2021, at 8:21:02

In reply to Re: Ritalin + an MAOi = Greater baseline D/NE? » undopaminergic, posted by linkadge on October 15, 2021, at 21:07:00

> These are mice with double or triple gene knockouts.

OK, the problem with that approach is that these mice grow up to have a different neurobiology. The differences develop to compensate for the missing genes. Compensatory changes can be very far-reaching. I read about animals (rats or mice) that lacked a central (CNS) serotonergic system, and they survived!

> The problem is that the reuptake process is also needed for the recycling of the neurotransmitter.
>

Yes, but this does not appear to seriously deplete the stores of the neurotransmitter, at least not the way reserpine or amphetamine can do.

> So blocking reuptake does cause activation of the inhibitory autoreceptors slowing firing, but also blocking the resorption of the neurotransmitter for subsequent re-release.
>
> Many reuptake inhibitors do more to 'stabilize' monoamine activity than really enhance it. The exception is the stimulants with a more complex mode of action.
>

Well, the reuptake inhibitors can increase synaptic monoamine content with over 100%. That would surely boost the neurotransmission. Perhaps you mean that reuptake inhibitors only enhance existing, endogenous signals, and does not itself induce the neurons to fire, although they can boost weak signals that would not otherwise go through.

-undopaminergic


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