Posted by PeterJ on April 25, 2000, at 3:44:51
In reply to Re: Amineptine: what does this mean: Scott, CamW, posted by Scott L. Schofield on April 21, 2000, at 17:23:39
May I add a few comments to Scott's excellent response.
(I am sure Scott knows all this, but it's an interesting topic.)Many antidepressants down-regulate beta-adrenergic receptors
by inhibiting NE uptake and thus increasing NE levels at the synapse.
However, other antidepressants may down-regulate beta receptors by
more indirect means. For exampe sulpiride down regulates beta
receptors. This is believed to occur because it blocks pre-synaptic
dopamine heteroreceptors on NE neurons. The DA receptors inhibit
NE release so blocking them may increase NE release.
The most important indirect effect on NE receptors occurs via
the serotonin system. Most, if not all, SSRIs (there is some variation
among studies) down-regulate beta adrenergic receptors after chronic
administration in animals. If you lesion the serotonergic system, this
down-regulation does not occur. What is even more interesting is that
serotonergic lesions also prevent the down-regulation produced by
noradrenergic antidepressants such as desipmramine and other TCAs.
It appears that 5-HT2 receptors have a necessary role in the
regulation of beta adrenergic receptors.
One antidpressant which still produces beta receptor down-
regulation in serotonin lesioned animals is clorgyline. It is
hypothesized that clorgyline has such a powerful effect on serotonin
levels that it overcomes the effect of the lesions of the sertonin
system (Aulakh et al. Role of serotonergic input in the down-regulation
of beta-adrenoceptors following long term clorgyline treatment.
Eur J Pharmacol 1988 Oct 26;156(1):63-70)
ECT and Transcranial Magnetic Stimulation also down-regulate
these receptors.
Early on (1975) it was proposed that beta adrenergic down-regulation
was a common factor in all effective antidepressant treaments. This may
not be the case as at least one antidepressant does not seem to down-
regulate beta receptors--bupropion. It is still true, however that almost
all effective antidepressants down-regulate beta adrenergic receptors in
rats. It's assumed this happens in humans as well, but we really don't know.Peter
poster:PeterJ
thread:30864
URL: http://www.dr-bob.org/babble/20000420/msgs/31212.html