Geoffrey,

The following words from this abstract hold the most promise of
anything I have read relative to understanding intense daily
flushing:

"Together with unselective agonists,
these new tools have helped to reveal the 5-HT7 receptor
distribution in more detail. Important functional roles for the 5-
HT7 receptor in thermoregulation, circadian rhythm ..."

Hopefully, in a few years, people will look back and realize that
using SSRIs and SNRIs to go after 5-HT2A (not 5HT7)receptors in
hopes of stablizing hypothamalic thermoregulation was only touching
the surface of the real problem. My experience with Effexor in this
regard is that it is a mis-directed sledge hammer. Given all the
advances alluded to in this abstract, one can hope that these
new 'tools' can probe (and impact) much more selectively that the
rather crude approaches at our disposal today.

IMHO, the first grant proposal funded by RRF should pursue precisely
the line of thinking advanced in the abstract below. I have always
believed that control of hypothalamic setpoints (and the width of
the regulatory zone) is where the real insight will be found.

Thanks.

Rick


--- In rosacea-support@yahoogroups.com, "Dr. Geoffrey Nase, PhD"
<drnase1000@h...> wrote:
>
>
> Selectively controlling the hypothalamus – Decreasing
hypothalamus-
> mediated Flushing
>
> Scientists have identified a key receptor in the hypothalamus that
> helps regulate skin flushing to heat and developed a selective
> blocker for this receptor. It also aids in treating depression.
> This is the single most important finding to date regarding
possible
> treatment of thermoregulatory disturbances in rosacea – e.g.
> flushing to internal heat, flushing to changes in basal metabolic
> rate, flushing when the hypothalamus setpoint is wrong or altered,
> flushing to external heat, exercise, intimate relations, etc. One
> to follow closely.
>
> Regards,
>
> Geoffrey
> ______________________________
>
> Dr. Geoffrey Nase
> Ph.D. Neurovascular Physiologist
> http://www.drnase.com
> ______________________________
>
>
>
> Trends Pharmacol Sci. 2004 Sep;25(9):481-6. Related Articles,
> Links
>
>
> Functional, molecular and pharmacological advances in 5-HT7
receptor
> research.
>
> Hedlund PB, Sutcliffe JG.
>
> Department of Molecular Biology, The Scripps Research Institute,
La
> Jolla, CA 92037, USA.
>
> The 5-HT7 receptor was among a group of 5-HT receptors that were
> discovered using targeted cloning strategies 12 years ago. This
> receptor is a seven-transmembrane-domain G-protein-coupled
receptor
> that is positively linked to adenylyl cyclase. The distributions
of
> 5-HT7 receptor mRNA, immunolabeling and radioligand binding
exhibit
> strong similarities, with the highest receptor densities present
in
> the thalamus and hypothalamus and significant densities present in
> the hippocampus and cortex. The recent availability of selective
> antagonists and knockout mice strains has dramatically increased
our
> knowledge about this receptor. Together with unselective agonists,
> these new tools have helped to reveal the 5-HT7 receptor
> distribution in more detail. Important functional roles for the 5-
> HT7 receptor in thermoregulation, circadian rhythm, learning and
> memory, hippocampal signaling and sleep have also been
established.
> Hypotheses driving current research indicate that this receptor
> might be involved in mood regulation, suggesting that the 5-HT7
> receptor is a putative target in the treatment of depression.