Psycho-Babble Medication Thread 1095398

Shown: posts 1 to 20 of 20. This is the beginning of the thread.

 

NE strengths of Reboxetine vs Atomoxetine

Posted by JohnBoy2000 on October 12, 2017, at 4:20:51

The IC 50 values I found for

Atomoxetine = 0.36 nM

Reboxetine = 8.2 nM

Perhaps there are more accurate IC50 values out there though.

Atomoxetine is dosed up to 100 mg
Reboxetine to 10 mg max.

Reboxetine supposedly failed clinical trials as an AD, but was approved anyways.

Atomoxetine supposedly failed clinical trails as an AD, but was approved for ADHD.


For myself - I've only ever responded to NE enhancing drugs so, I'm just looking for the most powerful one in that capacity.

According to them IC50 values - that would be atomoxetine, right?

 

Re: NE strengths of Reboxetine vs Atomoxetine JohnBoy2000

Posted by SLS on October 12, 2017, at 8:30:48

In reply to NE strengths of Reboxetine vs Atomoxetine, posted by JohnBoy2000 on October 12, 2017, at 4:20:51

If you are to remain focused on NE for depression, I recommend desipramine. It has been studied for decades. It also works for ADHD


- Scott


> Atomoxetine = 0.36 nM
>
> Reboxetine = 8.2 nM
>
> Perhaps there are more accurate IC50 values out there though.
>
> Atomoxetine is dosed up to 100 mg
> Reboxetine to 10 mg max.
>
> Reboxetine supposedly failed clinical trials as an AD, but was approved anyways.
>
> Atomoxetine supposedly failed clinical trails as an AD, but was approved for ADHD.
>
>
> For myself - I've only ever responded to NE enhancing drugs so, I'm just looking for the most powerful one in that capacity.
>
> According to them IC50 values - that would be atomoxetine, right?

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by JohnBoy2000 on October 12, 2017, at 8:54:38

In reply to Re: NE strengths of Reboxetine vs Atomoxetine JohnBoy2000, posted by SLS on October 12, 2017, at 8:30:48

> If you are to remain focused on NE for depression, I recommend desipramine. It has been studied for decades. It also works for ADHD
>
>
> - Scott

Tried it already.

Hard drug, cardiac wise, plus, heavy sedation above the minimal dose, paradoxically causing insomnia if taken at night time.

Didn't agree with me.

Appreciate the suggestion but, after that, I try to focus on as selective an agent as possible.

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by linkadge on October 12, 2017, at 15:03:30

In reply to NE strengths of Reboxetine vs Atomoxetine, posted by JohnBoy2000 on October 12, 2017, at 4:20:51

Possibly.

According to Wikipedia,

Atomoxetine NET ki 5
Reboxetine NET ki 13.4

The problem with ki, is it connects the binding of the molecule to the concentration of the drug. The issue with this, is that taking 10mg of either drug, wouldn't necessarily result in the same drug concentration in the brain. The concentration is affected by rate of absorption, elimination half-life, brain penetrability etc.

My guess is that higher doses of atomoxetine are needed because it isn't as well absorbed as reboxetine, but I have no idea.

Linkadge


 

Re: NE strengths of Reboxetine vs Atomoxetine JohnBoy2000

Posted by MightyKondrian on October 14, 2017, at 13:37:40

In reply to Re: NE strengths of Reboxetine vs Atomoxetine, posted by JohnBoy2000 on October 12, 2017, at 8:54:38

> > If you are to remain focused on NE for depression, I recommend desipramine. It has been studied for decades. It also works for ADHD
> >
> >
> > - Scott
>
>
>
> Tried it already.
>
> Hard drug, cardiac wise, plus, heavy sedation above the minimal dose, paradoxically causing insomnia if taken at night time.
>
> Didn't agree with me.
>
> Appreciate the suggestion but, after that, I try to focus on as selective an agent as possible.

Strange answer. Nothing paradoxical about it keeping you awake. Its an NRI. It should promote wakefulness at least. Sedation shouldn't happen either. Its a metabolite of Lofepramine, a drug which helps stamina and focus. NEVER found Lofepramine sedating. Although I dont take it with my MAOI it is my 2nd fave drug (better than clonazepam for me). Really helps my bad procrastination.
I guess we are all (oddly) different.

MightyKondrian.

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by linkadge on October 14, 2017, at 14:59:27

In reply to Re: NE strengths of Reboxetine vs Atomoxetine JohnBoy2000, posted by MightyKondrian on October 14, 2017, at 13:37:40

I find that nortriptyline is more sedating than SSRIs.

Mind you, it has some anti-histamine, anti-serotonin effects.

The thing with NRIs is that, norepinephrine reuptake inhibition doesn't necessarily promote norepinephrine release. In fact, in the short term at least, it might decrease norepinephrine release via inhibitory feedback receptors.

I find that nortriptyline helps me sleep. Although, I may have some ADHD, in which case the drug is 'calming' me by addressing ADHD symtpoms.

Linkadge

 

Re: NE strengths of Reboxetine vs Atomoxetine linkadge

Posted by MightyKondrian on October 14, 2017, at 15:16:06

In reply to Re: NE strengths of Reboxetine vs Atomoxetine, posted by linkadge on October 14, 2017, at 14:59:27

> I find that nortriptyline is more sedating than SSRIs.
>
> Mind you, it has some anti-histamine, anti-serotonin effects.
>
> The thing with NRIs is that, norepinephrine reuptake inhibition doesn't necessarily promote norepinephrine release. In fact, in the short term at least, it might decrease norepinephrine release via inhibitory feedback receptors.
>
> I find that nortriptyline helps me sleep. Although, I may have some ADHD, in which case the drug is 'calming' me by addressing ADHD symtpoms.
>
> Linkadge

Nortriptyline is anti-histaminic, you just said it. Thats not its main therapeutic effect. Its a side effect. Also its effect on your possible ADHD symptoms would fit right, being an NRI. It all adds up.
Just my calculated view ;)

Mighty Warrior

 

Re: NE strengths of Reboxetine vs Atomoxetine linkadge

Posted by MightyKondrian on October 14, 2017, at 15:26:45

In reply to Re: NE strengths of Reboxetine vs Atomoxetine, posted by linkadge on October 14, 2017, at 14:59:27

> The thing with NRIs is that, norepinephrine reuptake inhibition doesn't necessarily promote norepinephrine release. In fact, in the short term at least, it might decrease norepinephrine release via inhibitory feedback receptors.

This is kinda tricky for me. Are you saying that the receptor tells itself that it has enough noradrenalin (I'm British) in the synapse and tells itself to stop producing more, in the short term?
Explain a little more please. I know so much but never claim myself to know everything lol

MightyKondrian

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by phidippus on October 15, 2017, at 8:58:48

In reply to NE strengths of Reboxetine vs Atomoxetine, posted by JohnBoy2000 on October 12, 2017, at 4:20:51

So let me get this right. You're trying to treat depression with an NET inhibitor alone? How is that working out for you?

Eric

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by JohnBoy2000 on October 16, 2017, at 14:08:18

In reply to Re: NE strengths of Reboxetine vs Atomoxetine, posted by phidippus on October 15, 2017, at 8:58:48

> So let me get this right. You're trying to treat depression with an NET inhibitor alone? How is that working out for you?
>
> Eric


Why - are you referring to the lack of autoreceptor blockade via NRI alone.

Or noradrenaline in stand alone not being effective?

Chronic lethargy is my primary symptom - NA is the only thing that works for me.

However - 90% receptor occupancy for efficacy is extremely difficult to achieve, without going too far - thus, exacerbating the lethargy.

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by phidippus on October 16, 2017, at 14:32:07

In reply to Re: NE strengths of Reboxetine vs Atomoxetine, posted by JohnBoy2000 on October 16, 2017, at 14:08:18

AH, considering your primary symptom, I can see why the focus on noradrenaline. But there has to be something else you respond to. How about GHB? Stimulants?

Eric

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by linkadge on October 16, 2017, at 15:50:10

In reply to Re: NE strengths of Reboxetine vs Atomoxetine linkadge, posted by MightyKondrian on October 14, 2017, at 15:16:06

Yeah, sometimes when I couldn't sleep, Ritalin helped.

Linkadge

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by linkadge on October 16, 2017, at 16:00:40

In reply to Re: NE strengths of Reboxetine vs Atomoxetine linkadge, posted by MightyKondrian on October 14, 2017, at 15:26:45

I am not an expert either, but there are post-synaptic receptors (the ones that exert the main effect of the neurotransmitter) and there are pre-synaptic autoreceptors and heteroreceptors which affect the release of the neurotransmitter.

So, for example, if you take a reuptake inhibitor, you immediately increase the amount of neurotransmitter in the synapse. However, this activates the post-synaptic receptors and the autoreceptors. When the autoreceptors are activated, this slows the firing / release of the neurotransmitter from the presynaptic neuron.

Over time, the autoreceptors can desensitize which can result in increased firing.

Take, for example clonidine. It is a blood pressure medication which slows the release of norepinephrine. It does this by activating a specific norepinephrine autoreceptor (alpha-2). This receptor can also be activated by norepinephrine itself to slow the release of more neurotransmitter.

Mirtazapine and yohimbine block this same adrenaline receptor, which increases the firing of norepinephrine.

Basically, the autoreceptors work to control the amount of neurotransmitter in the synapse. They respond when the amount of neurotransmitter becomes elevated to slow the amount released.

Serotonin and dopamine also have autoreceptors which respond to serotonin and dopamine by releasing less neurotransmitter.

Linkadge


 

Re: NE strengths of Reboxetine vs Atomoxetine linkadge

Posted by MightyKondrian on October 16, 2017, at 16:15:45

In reply to Re: NE strengths of Reboxetine vs Atomoxetine, posted by linkadge on October 16, 2017, at 16:00:40

Thanks linkadge. I kinda got it lol. Will give it a few more reads when I'm not so tired ;)

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by SLS on October 16, 2017, at 18:56:39

In reply to Re: NE strengths of Reboxetine vs Atomoxetine linkadge, posted by MightyKondrian on October 16, 2017, at 16:15:45

Hi.

Heteroreceptors for a given neurotransmitter are located on the membranes of neurons that use another neurotransmitter for synaptic messaging. For instance, a dopaminergic neuron may have serotonin receptors (heteroreceptors) along its axon that serve to inhibit its firing (action potential propogation). In this way, serotonin can serve to inhibit or "calm" excessive dopamine or norepinephrine activity that may be occurring in fear or anxiety centers in the brain, including the amygdala. Serotonin 5-HT1a receptors often perform this function. Similarly, serotonin 5-HT1a heteroreceptors modulate activity in the prefrontal cortex (PFC) and hippocampus. More recently, it has been observed that 5-HT7 heteroreceptors exist that could be implicated in mood, anxiety, and OCD disorders. This elegant network of stimulatory and inhibitory interactions creates a dynamic that makes it impossible to understand the brain by thinking in terms of chemistry without considering its circuitry.


- Scott

 

WOW thanks! (nm) SLS

Posted by MightyKondrian on October 16, 2017, at 20:43:31

In reply to Re: NE strengths of Reboxetine vs Atomoxetine, posted by SLS on October 16, 2017, at 18:56:39

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by linkadge on October 17, 2017, at 17:24:08

In reply to Re: NE strengths of Reboxetine vs Atomoxetine, posted by SLS on October 16, 2017, at 18:56:39

Ah. There you go. Thanks for the clarification.

Now that you mention it, I recall this (that heteroreceptors respond to a different neurotransmitter than they control).

I suppose the 'presynaptic autoreceptors' are the ones that I am referring to.

If I recall, buspirone has some antagonist activity at dopamine presynaptic autoreceptors.

Linkadge

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by linkadge on October 17, 2017, at 17:25:22

In reply to Re: NE strengths of Reboxetine vs Atomoxetine, posted by SLS on October 16, 2017, at 18:56:39

The 5-ht2c receptors do this too (i.e. reduce dopamine release), but I don't think they are considered heteroreceptors. Although, I have no idea really!

I have only a cursory knowledge.

Linkadge

 

Re: NE strengths of Reboxetine vs Atomoxetine linkadge

Posted by MightyKondrian on October 18, 2017, at 6:26:36

In reply to Re: NE strengths of Reboxetine vs Atomoxetine, posted by linkadge on October 17, 2017, at 17:24:08

Ah yes, buspirone. I've taken this before when switching MAOIs. Was very sad while taking it but would have probably been with anything if switching.
out of interest, can it be taken safely with irreversible MAOIs? Would be nice in my armory. Along with lithium.
Sorry to sidetrack

MightyKondrian

 

Re: NE strengths of Reboxetine vs Atomoxetine

Posted by linkadge on October 20, 2017, at 18:17:55

In reply to Re: NE strengths of Reboxetine vs Atomoxetine linkadge, posted by MightyKondrian on October 18, 2017, at 6:26:36

I have tried buspirone about 3 times with limited success. It's weird because it works very well for me (soon after dosing), but I get nasty rebound about hours later (with worse anxiety).

It has some metabolites which can produce weird reactions. I don't think there are any interactions with MAOIS.

On paper, there might be a contraindication, but I've never heard of an actual reaction in practice. It doesn't affect serotonin metabolism, it just interacts with one receptor.

Linkadge



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