Psycho-Babble Medication Thread 1109518

Shown: posts 1 to 9 of 9. This is the beginning of the thread.

 

Amitriptyline and percentages of SERT blockade

Posted by Skeletor on April 10, 2020, at 12:12:07

Can you reach clinically significant SERT blockade [~ 80%] with Amitriptyline?

According to P. K. Gillman and others the tricyclic antidepressant Amitriptyline is a weaker SRI than SSRIs / SSNRIs and Clomipramine / Imipramine. It seems that with Amitriptyline it is difficult to reach Serotonin Toxicity; that's why you can safely combine Amitriptyline with MAOIs.

My question: What is the maximal SERT blockade possible with Amitriptyline standalone? Is there a dosage-SERT-occupation-curve? It surely depends on the individual genetic makeup (slow, intermediate, rapid metabolizer) and other genetic factors, but there surely are median values available? I would be interested to learn if one can reach 80% SERT blockade with Amitriptyline alone (at higher dosages).

https://abload.de/img/curve-kopieyukwv.png

 

Re: Amitriptyline and percentages of SERT blockade

Posted by linkadge on April 10, 2020, at 16:41:21

In reply to Amitriptyline and percentages of SERT blockade, posted by Skeletor on April 10, 2020, at 12:12:07

According to Wikipedia, amitriptyline dose have significant affinity for the serotonin transporter (more so than the norepinephrine transporter), but probably 10x weaker than clomipramine.

There are differences in the way that drugs bind to the serotonin transporter, however (different binding sites which may make one drug not directly comparable to another). For example, escitalopram binds to the allosteric site SERT which can enhance the effective inhibition.

As far as why it is less likely to cause serotonin syndrome, who knows. Some of the serotonin antagonism may reduce it.

For amitriptyline the affinity of SERT to 5-ht2a is 6. For clomipramine, it is 150. The relatively higher affinity for 5-ht2a may offset some of the SERT effect (preventing serotonin syndrome).

Linkadge

 

Re: Amitriptyline and percentages of SERT blockade linkadge

Posted by Skeletor on April 10, 2020, at 17:21:58

In reply to Re: Amitriptyline and percentages of SERT blockade, posted by linkadge on April 10, 2020, at 16:41:21

> According to Wikipedia, amitriptyline dose have significant affinity for the serotonin transporter (more so than the norepinephrine transporter), but probably 10x weaker than clomipramine.
>
> There are differences in the way that drugs bind to the serotonin transporter, however (different binding sites which may make one drug not directly comparable to another). For example, escitalopram binds to the allosteric site SERT which can enhance the effective inhibition.
>
> As far as why it is less likely to cause serotonin syndrome, who knows. Some of the serotonin antagonism may reduce it.
>
> For amitriptyline the affinity of SERT to 5-ht2a is 6. For clomipramine, it is 150. The relatively higher affinity for 5-ht2a may offset some of the SERT effect (preventing serotonin syndrome).
>
> Linkadge
>
>
>
>

Thanks for your response. It indeed would make sense. 5HT2 and 5HT3 antagonists seem to attenuate Serotonin toxicity.

Found this, but not sure how legit it is: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409583/

 

Re: Amitriptyline and percentages of SERT blockade

Posted by linkadge on April 11, 2020, at 10:39:45

In reply to Re: Amitriptyline and percentages of SERT blockade linkadge, posted by Skeletor on April 10, 2020, at 17:21:58

Yeah, cyproheptadine is structurally similar to the TCAs. It has similar serotonin, histamine, acetylcholine blocking effects and some (very weak serotonin reuptake inhibition) and is useful for serotonin syndrome.

Most psychiatrists would still likely NOT prescribe amitriptyline with an MAOI, but Gillman is supposedly an expert in this field and his clinical / research experience is important.

I wonder if depression severity correlates with the likelihood of serotonin syndrome. Not that depression is really conclusively linked to low serotonin, but for some (with really low serotonin levels) combining SSRIs and MAOIs may not lead to a problem.

Interestingly, coffee and tobacco can inhibit MAO. Smokers probably have a ~50% reduction in MAO levels yet I've never heard of smoking causing serotonin syndrome with SSRIs.

Linkadge

 

Re: Amitriptyline and percentages of SERT blockade

Posted by undopaminergic on April 11, 2020, at 12:00:50

In reply to Re: Amitriptyline and percentages of SERT blockade, posted by linkadge on April 11, 2020, at 10:39:45

>
> I wonder if depression severity correlates with the likelihood of serotonin syndrome. Not that depression is really conclusively linked to low serotonin, but for some (with really low serotonin levels) combining SSRIs and MAOIs may not lead to a problem.
>

Maybe, yes, but in all cases, it is the dose that makes the poison. Eg. if adding 50 mg of sertraline under MAO-A inhibition would precipitate serotonin syndrome, 5 mg may still be all right.

> Interestingly, coffee and tobacco can inhibit MAO. Smokers probably have a ~50% reduction in MAO levels yet I've never heard of smoking causing serotonin syndrome with SSRIs.
>

What about cocaine? It is a SRI for sure, but I never heard of serotonin syndrome from it. Perhaps it is self-limiting due to coke's short half-life?

-undopaminergic

 

Re: Amitriptyline and percentages of SERT blockade undopaminergic

Posted by linkadge on April 11, 2020, at 12:26:10

In reply to Re: Amitriptyline and percentages of SERT blockade, posted by undopaminergic on April 11, 2020, at 12:00:50

>What about cocaine? It is a SRI for sure, but I >never heard of serotonin syndrome from it. Perhaps >it is self-limiting due to coke's short half-life?

True. And I'm sure there are tons of people that smoke (MAOI) and use cocaine. Although, I have read about case reports where adding methylphenidate to a particular regime has resulted in serotonin syndrome. My theory for this is that, when serotonin reuptake inhibition gets high, there is evidence that the dopamine transporter can begin to take up serotonin and that this might be the causative mechanism.

"They found that higher serotonin concentrations caused by SSRIs can "trick" transporters of another key neurotransmitter, dopamine, into retrieving serotonin into dopamine vesicles. "

https://www.eurekalert.org/pub_releases/2005-04/cp-sai040105.php

So, perhaps adding a dopamine reuptake inhibitor to an SSRI could actually further augment serotonin levels.

Linkadge


 

Re: Amitriptyline and percentages of SERT blockade undopaminergic

Posted by SLS on May 9, 2020, at 11:24:53

In reply to Re: Amitriptyline and percentages of SERT blockade, posted by undopaminergic on April 11, 2020, at 12:00:50

Combining an irreversible MAOI that inhibits MAO-A with a potent serotonin reuptake inhibitor is the most dangerous combination of antidepressants that I can think of. I know this from personal experience (Parnate + single a small dose of Effexor).

Is tobacco a potent inhibitor of MAO-A?


- Scott

 

Re: Amitriptyline and percentages of SERT blockade Skeletor

Posted by SLS on May 9, 2020, at 11:35:50

In reply to Amitriptyline and percentages of SERT blockade, posted by Skeletor on April 10, 2020, at 12:12:07

> Can you reach clinically significant SERT blockade [~ 80%] with Amitriptyline?

I can't answer your question. However, I would mention that Nardil 45mg/day + amitriptyline 150mg/day did not cause serotonin syndrome. Perhaps the dosage of Nardil was too low to produce a reaction. With a higher dosage, I had a reaction when imipramine was chosen to combine with it. Muscle rigidity was the most prominent symptom.


- Scott

 

Re: Amitriptyline and percentages of SERT blockade SLS

Posted by undopaminergic on May 9, 2020, at 12:16:09

In reply to Re: Amitriptyline and percentages of SERT blockade undopaminergic, posted by SLS on May 9, 2020, at 11:24:53

> Combining an irreversible MAOI that inhibits MAO-A with a potent serotonin reuptake inhibitor is the most dangerous combination of antidepressants that I can think of. I know this from personal experience (Parnate + single a small dose of Effexor).
>

I agree. I was just saying the dose makes the poison. How dangerous is 5 mg sertraline when added to a fully MAO-inhibitory regimen?

> Is tobacco a potent inhibitor of MAO-A?

https://www.ncbi.nlm.nih.gov/pubmed/11343627
Cite: "Smokers have 30-40 % lower MAOB and 20-30 % lower MAOA activity than non-smokers."

-undopaminergic


This is the end of the thread.


Show another thread

URL of post in thread:


Psycho-Babble Medication | Extras | FAQ


[dr. bob] Dr. Bob is Robert Hsiung, MD, bob@dr-bob.org

Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.