Posted by JohnX on October 24, 2001, at 22:30:01
In reply to Re: Nierenberg - Clonidine for bipolar depression? » JohnX, posted by Mitch on October 23, 2001, at 23:41:11
Mitch,
I read a paper on the proposed mechanism of
Wellbutrin, but I don't remember the details
off the top of my head. I believe the partial jist of
it was that the norepinephrine reuptake inhibition
causes the alpha-2 adrenoreceptors to downregulate
long term. I.e. they become less sensitive to
repeated exposure to norepinephrine in the synapse,
thus boosting norepinephrine levels because of
the reuptake inhibition but curbing
the rate of firing of the neurons themselves due
to the alpha-2 downregulation.Alpha-2 antagonists have often been a test for
panic attacks which would indicate symtoms of
post traumatic stress disorder. Yohimbine is
a very powerful alpha-2 antagonists that will
oftern times induce a panic attack in many people.
For these types of patients alpha-2 agonists are helpfull. This
would include Clonidine (Catapres) and Guanfacine
(Tenex). These meds are generally anxiolytic
, sometimes used to detox from benzodiazepines and
also control hyperactivity disorders (as in ADHD),
and can be taken concurrently with other anti-depressants.If you are curious about any other meds effect in
the brain's locus coerulus (the area I am referring too),
I can probably dig it up.-john
> >
> > Heres what happens with things like Remeron,
> > in case you are interested. The alpha-2 antagonism
> > increases firing in an area of the brain predominately
> > associated with (nor)adrenaline and the flight,or,
> > fight mechanism. These nerve impulses actually
> > propogate to serotonin neurons and increasing
> > the firing rate of some serotonin neurons.
> > The Remeron has a property that blocks a particular
> > type of sertonin receptor (the 5ht-2 series), generally
> > associated with anxiety. The increased serotonin
> > firing hits the other receptors and a balance is
> > supposed to be achieved that reduces anxiety in the
> > net. But the two areas of the brain , the one with
> > the noradrenaline, and the one with serotonin projections
> > can reactly very differently amongst different people.
> > In particular people with stress disorders will probably
> > be hyperactive on the noradrenergic path and may
> > experience anxiety on remeron.
> >
> > Interestingly, Buspar attempts
> > to decrease the firing rate of those serotonin neurons
> > to decrease anxiety, but one of its side metabolites
> > is an alpha-2 antagonist. I think this could kill
> > some of its anti-anxiety potential, but at higher
> > doses for some people the alpha-2 antagonism is
> > actually an anti-depressant (probably for people
> > who aren't generally anxious too).
> >
> > -john
>
>
> Well, it obviously turns on the *fight* response! I really felt concerned about the level of hostility I was experiencing with Remeron (and with Buspar). I was having fantasies about all sorts of violence. It almost became obsessive. I had several heated arguments (over nothing, really) at work that made me worried about getting fired. I really felt I had little control over physically assaulting somebody. The only time that happened (in an impulsive manner) was when I was in my early 20's and my Dad jumped my ass about something relatively piddly and I sucker-punched him. At the time I was being prescribed Valium and it seemed to make me very hostile occasionally. The ADHD I was dx'ed with (a few years ago)seems to fits this paradoxical reaction pattern. The only meds that I have ever found truly dangerous (in grave lack of impulse control) were Remeron, Buspar, Valium.
>
> My question is do you have any more detail about how Wellbutrin *inhibits* NE firing with respect to the area of the brain you talked about earlier?
>
> Mitch
poster:JohnX
thread:81697
URL: http://www.dr-bob.org/babble/20011015/msgs/82235.html