Posted by johnX2 on March 13, 2002, at 7:23:48
In reply to Re: High Dose Prozac » Psydoc, posted by SLS on March 12, 2002, at 6:07:14
Hi Scott,Tecnically....
If I'm reading this correctly the high dose Parnate does not "antagonize" so to speak the 5-ht2 receptors.
It was my thought that an antagonist such as Serzone or Remeron is a chemical that would bind to the receptor but not activate the receptor and "block-out" serotonin.
(Note: it does however downregulate the receptor, i.e desensitize it over time..just to confuse you).However for regular SSRIS, MAOIS, over time, it was my understanding that larger pools of the serotonin monoamine in the synaptic cleft may desensitize (or decrease the number of receptors) for a particular subclass such as the 5-ht2 through a genomic mechanism.
This would leave a fewer number of receptors
for available serotonin to bind too. This delay
may account for the time for an anti-depressant
response.If I'm interpreting this abstract correctly, the
Parnate is NOT an antagonist, but merely desensitizes the 5ht-2 site.Sorry if I type to much, I know it makes you
more depressed. Me too at times.Hang in there buddy!
Best wishes
John
> Hi.
>
> I suffer from a severe bipolar depression that has been unremitting for over ten years. I have experienced dramatic responses to a few classic antidepressant medications, but they last for only hours or days. Still, these brief "awakenings" occur only after having taken these drugs for two weeks, as one would expect. It is an uncommon presentation for which severe mania occurs only in conjunction with antidepressant use. I have tried high- dosage Parnate several times, but thus far it has represented a dead-end, even when combined with tricyclics and stimulants. I must say, though, that I receive some benefit at 120mg that I do not at lower dosages (80mg or 100mg).
>
> I came across an abstract on Medline years ago that tried to investigate what actions Parnate produces at higher dosages that do not occur at lower dosages. They found that it acted to antagonize 5-HT2 receptors, a property shared by antidepressant drugs like Remeron and Serzone, and the atypical neuroleptics for which antidepressant properties have been demonstrated. Their results might have been errant, of course, and I don't know that any other experiments have performed to repeat them.
>
>
> - Scott
>
>
> ---------------------------------------------
>
> 168: J Neural Transm Suppl 1994;41:127-34
>
> Comparisons of the actions of high and low doses of the MAO
> inhibitor tranylcypromine on 5-HT2 binding sites in rat cortex.
>
> Goodnough DB, Baker GB
>
> Department of Psychiatry, University of Alberta, Edmonton, Canada.
>
> Tranylcypromine (TCP) is a commercially available antidepressant
> drug, and recent literature reports suggest that high doses of this
> drug may be particularly effective in treating refractory
> depression. Down-regulation of 5-HT2 receptors in rat cortex is an
> effect produced after chronic administration of several
> antidepressants, and we have conducted a chronic study comparing
> low- and high-dose TCP in this regard. Male Sprague-Dawley rats
> were administered TCP (0.5 or 2.5 mg/kg/day) or vehicle (distilled
> water) via Alzet minipumps implanted subcutaneously in the dorsal
> thoracic area. Groups of rats were killed 4, 10 or 28 days after
> pump implantation and whole cortex was dissected out and utilized
> for preparation of a membrane fraction. Binding studies were
> performed with this fraction using 3H- ketanserin as the
> radioligand. Down-regulation (decrease in Bmax) of the 5-HT2
> binding site was observed in high-dose animals after 10 and 28 days
> but not after 4 days. Low-dose TCP had no effect on 5-HT2 densities
> at any time interval. The affinity of 3H-ketanserin for the 5-HT2
> site was not affected by either dose at any time interval. These
> results suggest that down-regulation of the 5-HT2 site may
> contribute to the efficacy of high-dose TCP in the treatment of
> refractory depression.
>
> PMID: 7931218, UI: 95016589
poster:johnX2
thread:27771
URL: http://www.dr-bob.org/babble/20020313/msgs/97764.html