Posted by cybercafe on July 11, 2002, at 1:49:39
In reply to Some antidepressant theory, posted by Shawn. T. on July 10, 2002, at 17:16:30
>life experiences. Recent advances in neuroscience have lead me to believe that a more ideal antidepressant may have the following properties: serotonin reuptake inhibition, 5HT-2 antagonism, and 5HT-3 antagonism. Or possibly a
okay 5HT2 antagonism i think is a really good idea... not just because of
a. 5HT2 is responsible for anxiety, agitation, sexual side effets, weight gain
but also because
b. by antagonizing "bad" receptors, were there not be more available for "good" receptors?
and even more importantly
c. it may be that the nucleus accumbens, possibly globus pallidus, are responsible for feelings of joy, happiness, pleasure, everything good (except sexual pleasure which i believe occurs in the septal nuclei) ... i believe that firing of 5HT 2B and 2C reduce firing of dopamine neurons in the VTA (which leads to the nucleus accumbens)... also 5HT 2A inhibits striatal firing ...
now as for 5HT3... yes i hate constipation... but i believe 5HT3 actually increases dopamine function in the nucleus accumbens (a good thing)... so i'll keep that :) ...
>would guess that SSRI monotherapy may reduce norepenephrine levels, which may explain why the stronger SSRI's like Paxil are much more sedating than the weaker, especially Prozac which is activating."hmm... maybe... since there are feedback inhibitory pathways from the raphe nucleus (serotonin) to the locus ceruleus (norepenephrine)....
> 5-HT1a activation is one possible action in the brain thought to contribute to cortisol release.
yes... and cortisol is related to steroid diabetes and accelerated aging... these are bad things :)
>a quick rundown. I have found that 5-HT1a activation is an important antidepressant
are there 5ht1a postsynaptic receptors, or are they all autoreceptors?
> I would argue that tonic 5-HT1a receptor activation to reduce sensitivity helps to increase 5-HT release from neurons, which... well i don't think it necessarily increases release from neurons... but i think that there is greater release than when there is more sensitivity...
... i would imagine that reuptake inhibitors don't necessarily allow more neurotransmitter to be in the synaptic gap, .. but simply that they allow it to be there for longer...
>HT2 antagonist is the best explanation for most SSRI side effects. 5-HT3 antagonism is said to reduce nausea.
... yeah the 5ht2 family certaihly doesn't seem very nice...
5ht3 is responsible for nausea, emesis, and possibly IBS but i don't remember exactly
>Another possible explanation is its actions on noradrenergic function simply allow for greater 5-HT release.
i believe reading somewhere that it is because of ations on certain NE receptors... see above
> Remeron is particularly effective for depression based on its effects as a 5-HT2 antagonist and indirect 5-HT1 agonist. I believe its ability to fight depressive symptoms is partly because of effects on cortisol. Based on this, I hypothosized that a test for abnormally low cholesterol may be an indicator of depression, based on the fact that cholesterol is a precursor to the precursors of cortisol... i'm not sure remeron is one of the more powerful antidepressants...
... although i suspect it is quite useful in augmentation therapy...
poster:cybercafe
thread:111957
URL: http://www.dr-bob.org/babble/20020709/msgs/112012.html