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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 4 of 4. This is the beginning of the thread.
Posted by deniseuk190466 on April 23, 2008, at 13:13:21
Hi, Calling Scott/Linkadge/Bleauberry
Is this a safe combination?
Also, can somebody explain the below to me in layman's terms, like pretend I am a 10 year old child? It's mainly the bit about inhibiting the K+ current evoked realease of serotonin....well it's everything really. However, I do understand the bit about the Raphe Nuclei and Serotonin because I read about that yesterday :-)
Mirtazapine antagonizes alpha-2 adrenergic heteroreceptors on serotonergic neurons. This results in an inhibition of the K+ current evoked release of serotonin by neurons in the dorsal raphe nucleus (where the majority of serotonin neurons reside in the brain). An alternate pathway to enhanced serotonergic activity is through the activation of alpha-1 adrenoceptors mediating serotonin cell firing. These receptors will be indirectly activated as a result of the enhanced noradrenaline release caused by mirtazapine's antagonism of alpha-2 autoreceptors.
See De Boer et al. (1994) for verification.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7912194&dopt=AbstractThe combination of tianeptine and mirtazapine could be looked at from a few different directions, the REM augmentation idea is one. On the topic of a shared activity at the molecular level, they could hypothetically interact at the level of K+ current evoked release of serotonin. A similar situation takes place in a drug free individual as serotonin auto and heteroreceptors are affected through various pathways (in addition to positive affectors such as alpha-1 adrenoceptors).
Whitton et al. (1991) have shown that in the hippocampus, tianeptine reduces the K+ evoked rise in extracellular serotonin. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=2046875&dopt=Abstract
Now considering that tianeptine may reduce extracellular serotonin in some brain areas via K+ currents while mirtazapine could increase extracellular serotonin levels, the two drugs would potentially offset each other in a fashion similar to the effect seen when mixing tianeptine and the SSRI citalopram (Celexa). Thus, tianeptine might be seen as a way to "fine-tune" extracellular serotonin levels for a person taking mirtazapine. Ideally, the CNS should maintain a relative balance between low and high serotonin levels while a person is awake (serotonin levels drop during sleep). Low extracellular serotonin levels are generally associated with depression and high levels are generally associated with anxiety, this might be seen as a spectrum from low alertness to a high level of alertness.Thanks.....Denise
Posted by bleauberry on April 26, 2008, at 19:11:23
In reply to Tieneptine combined with Seroxat + chemicquestions, posted by deniseuk190466 on April 23, 2008, at 13:13:21
So sorry, but the K+ evoked release stuff is not something I have a good grasp of.
All I know is that in a reported case study on pubmed someone failed antidepressants and failed tianeptine, but responded with the combination. Unfortunately, no mention of what the antidepressant was that they combined with tianeptine.
Posted by deniseuk190466 on April 28, 2008, at 10:06:23
In reply to Re: Tieneptine combined with Seroxat + chemicquestions, posted by bleauberry on April 26, 2008, at 19:11:23
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Posted by cumulative on April 30, 2008, at 6:38:19
In reply to Tieneptine combined with Seroxat + chemicquestions, posted by deniseuk190466 on April 23, 2008, at 13:13:21
Unfortunately, I have to say that I've seen a study wherein the combination of tianeptine and SSRI abolished all anxiolytic effect from both agents.
I'll try and dig up the abstract for you ...
What sort of effects are you looking for with the combination, btw?
This is the end of the thread.
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