Posted by JohnX2 on November 10, 2001, at 21:11:39
more ramblings from the psychopharmacology nut.I'm looking at interactions in the brain between
the locus coerulus and the raphe serotonergic projections.These interactions are explained in
Steven Stahl's book and info I am
gathering from Medline. They explain how an
atypical med like Remeron may work.There are interactions between these two key pathways.
1) norepinephrine is released from the locus coerulus
(a major norephinephrine projection associated with
stress/fight or flight etc) onto
alpha-1 heteroreceptors located on cell bodies of somotodendric
raphe serotonin cell bodies. An alpha-2 antagonist like Remeron can
antagonize the presynaptic alpha-2 receptor at such a junction
between a synapse of a locus coerulus terminal and
thus release norepinephrine activating the alpha-1
receptors on the raphe somotodendric receptors.
These noradrenaline receptors on the somotodendric
raphe serotonin neurons "accelerate" the firing of
the raphe neurons.2) At the terminals of the raphe serotonergic projections,
one of which is the VTA (ventral tegmental area),
junctions between the terminal locus coerulus
neurons and raphe serotonergic neurons can cause
cut the a "brake cable" of serotonin release. This can occur
if the presynaptic alpha-2 autoreceptor on the
locus coerulus neuron is antagonized, releasing
noradrenaline that hits the post synaptic
alpha-2 hetero-receptors which "cut the brake
cable" to release more serotonin.
Suppose we don't want these actions, and want to
stabilize these interactions. Buspar is supposed
to in some cases reduce the firing of the raphe
serotonergic projections and Klonopin potently does
this. This results in decreased anxiety (and an
alleviation of tension headache for me and development
of tolerance to Adderall). I believe
the net affect on the post-synaptic serotonin neuron
at the VTA junction directly impacts the firing pattern
of the dopamine projections. I believe a downstream
sensitization or tolerance can occur if this interaction
between the locus coerulus and raphe serotonin projections
is not "balanced". This could occur if the locus
coerulus is "beat-up" especially while taking stimulants
or if it got goofed up by chronic stress.So, it is known that clonodine, a partial alpha-2
agonist and postsynpatic alpha-2 antagonist can help
with benzo withdrawl. But I'm proposing a more insane
idea whereby an alpha-1 antagonist like Prazosin is
combined with a alpha-2 agonist like Tenex to help
"tweak" or stabilize if you will these interactions.
Does anyone believe such an approach, if one found
the right dosing could be effective for PTSD,med
poop out, anxiety? Cam,Jgalt,SLS, etc?care to chime in on my hair-brained scheme. I'm
coming up with lots of them lately.-john
poster:JohnX2
thread:83830
URL: http://www.dr-bob.org/babble/20011104/msgs/83830.html