Posted by JohnX2 on November 17, 2001, at 9:36:17
This is quite technical, but for those who are
interested:There was a new article in psychopharmocology
on Wellbutrin's mode of action.Basically came to some of the same conclusions as
another article I read, but also came up with 1 more
piece of data which I always thought would be true:
Bupropion increases serotonin conductance!I thought this may be true and I don't have the
whole article, but the abstract points out that
bupropion increases NA levels in the locus coerulus
and inhibits firing. This was antagonized by
idazoxan (alpha-2 antagonist).
At the higher doses the mean firing rate of serotonin
neurons (I'm assuming in the dorsal raphe) was
increased by 100%. The dopamine firing pattern in the
VTA was not affected. In the other articles I read
on bupropion and zoloft, the vta firing pattern was
very moderately dampened. I have a theory that in
some of us (i.e. me), the vta firing pattern
is severely dampened. Leading to bruxism or tension headaches and emotional
numbing. I also theorize that an nmda antagonist
i.e. memantine may stabilize the vta firing and
provide a sustained anti-depressant effect.Also, this would indicate the an 5ht-2a antagonist and/or
an alpha-1 antagonist would antagonize the bupropion
induced increased in serotonin conductance, which
I believe Zyprexa is doing for me since I can tolerate
a low dose of buprion while on zyprexa.The increased serotonin firing in the dorsal raphe
likely comes from alpha-1 adrenoreceptors located
on the raphe somotodendric cell bodies. At these sights
noradrenaline (diffused from the locus coerulus) increases
the firing of serotonin. This is explained in Stephen
Stah'l Essential Psychopharmacology book when he
looks at Remeron. I would also suspect therfore that
there could be interactions at the serotonin nerve
endings that have alpha-2 heteroreceptors that brake
5ht release. Here any extra noradrenaline would brake
the release of serotonin. Hmm, more conductance but
less serotonin released. Interesting battle.Anyways, confirms my feeling regarding interactions
between the locus coerulus and the raphe projections.Most other NE reuptake blockers leave unaltered the
serotonin conductance. The abstract theorizes that
Wellbutrin therefore is more of a NE release inhancer
than a reuptake inhibitor (why?). My one failed trial
on WB I was also taking buspar, I think the buspar
action would work the opposite of what WB wanted to
do since buspar is an alpha-2 antagonist, etc. Hmmm.original investigation: Modification of norepinephrine and serotonin, but not
dopamine, neuron firing by sustained bupropion treatmentJianming Dong, Pierre Blier
Department of Psychiatry and Neuroscience, McKnight Brain Institute, University of Florida, P.O. Box 100256, Gainesville, FL 32610, USA
Phone: +1-352-392-3681 Fax: +1-352-392-2579Received: 12 June 2000 / Accepted: 20 November 2000 / Published online: 14 March 2001
Abstract. Rationale: Bupropion is widely used in the treatment of depression and as an anti-craving medication for the cessation of tobacco
smoking. Because it is a very weak inhibitor of norepinephrine (NE) and dopamine (DA) reuptake, its mechanisms of action remain to be
elucidated. Methods: Bupropion was administered subcutaneously via osmotic minipumps over 2 days to determine its effects on the
spontaneous firing activity of NE, serotonin (5-HT), and DA neurons in the brain of anaesthetised male Sprague-Dawley rats. This treatment
was used in order to obtain levels of the parent compound and its putatively active metabolites that would more adequately reflect the clinical
condition than utilizing acute injections. Results: When given by minipump for 2 days, bupropion produced a dose-dependent attenuation of
the mean spontaneous firing NE neurons (7.5 mg/kg per day: 15%; 15 mg/kg per day: 61%; 30 mg/kg per day: 80%) which was reversed by
the < alpha >2-adrenoceptor antagonist idazoxan. At the highest regimen, the mean firing rate of 5-HT neurons was 100% higher than in control
rats, but unaffected in NE-lesioned rats. In contrast, DA neurons in the ventral tegmental area displayed a normal firing rate during the latter
bupropion treatment. Conclusions: Sustained bupropion administration decreased the firing rate of NE neurons due to an increased
activation of their inhibitory somatodendritic < alpha >2-adrenoceptors. This effect of the bupropion treatment would be attributable mainly to
an enhancement of NE release and not to reuptake inhibition. This contention is based essentially on the observation that NE reuptake
blockers leave unaltered the firing rate of 5-HT neurons, whereas bupropion enhanced it via a NE-dependent mechanism. The present study
did not put into evidence any DA activity of bupropion at the level of the cell body of mesolimbic/cortical DA neurons at a regimen exerting
profound alterations of the firing activity of NE and 5-HT neurons.Keywords. Antidepressant · Locus coeruleus · Dorsal raphe · Ventral tegmental area · < alpha >2-Adrenoceptors and autoreceptors
poster:JohnX2
thread:84499
URL: http://www.dr-bob.org/babble/20011113/msgs/84499.html