Posted by SLS on March 12, 2002, at 6:07:14
In reply to Re: High Dose Prozac, posted by Psydoc on March 7, 2002, at 4:46:24
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:SLS
thread:27771
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