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5HT2A-antagonism + 5HT2C-agonism Would Be Ideal

Posted by Brainbeard on May 28, 2010, at 15:17:55

In reply to Lisuride, incredible potential, posted by CrAzYmEd on May 24, 2010, at 22:41:53

I found a very interesting article on the interplay between unspecific 5HT activation and 5HT2A-activation or blocking as well as 5HT2C-agonism or antagonism:

http://www.nature.com/npp/journal/v28/n2/full/1300057a.html

There is a consesnus based on clinical evidence that 5HT2A-agonism opposes the beneficial effects of unspecific 5HT-activation through serotonin reuptake inhibition (SRI). Thus, 5HT2A-antagonists have been shown to fasten and boost the efficacy of SSRI's. The indirect agonism of 5HT2A receptors by SSRI's is a mechanism that inhibits c.q. defeats the benefits of agonism of other 5HT receptors, probably most notably 5HT1A-receptors.

5HT2A-agonism leads to sexual dysfunction and anxious moods.
In the article mentioned above it's also stated that 5HT2A-agonism promotes glutamate release.

5HT2A and 5HT2C receptors have opposing functions in several ways. 5HT2C-agonism has shown to have antidepressant potential. It increases exuality. 5HT2C-antagonism may inhibit the benefits of 5HT2A-antagonism! This is an interesting find since most 5HT2A-antagonists are also 5HT2C-antagonists at least to some degree.

I have become convinced that several of the start-up effects that I typically experience when starting escitalopram are due to 5HT2C-agonism. The first days on escitalopram, and after raising the dose, I have a feeling that resembles my experiences on magic mushrooms. Time is being stretched out immensely: hours last extremely long and I can't believe what the clock is telling me. My appetite is suppressed - a known effect of 5HT2C-agonism. I feel euphoric and hyperseuxal.This must be 5HT2C-agonism!

If lisuride would be an ideal drug, it would at least have to be a 5HT2A-ANTAGONIST and a 5HT2C-agonist. Since it appears to be a stronger 5HT2A-agonist than a 5HT2C-agonist, these two mechanisms will downplay each other's benefits.

Fluoxetine/Prozac, by the way, of course has antidopaminergic properties, like any SSRI. Serotonin puts a brake on dopamine, to put it simply. Prozac causes sexual dysfunction like any other SSRI. It elevates prolactin levels like any other SSRI, which is also an antidopaminergic feature.


Current meds: 10mg melitracene + 0.5mg flupentixol; sertraline 100mg; amitriptyline 25mg; gabapentin (Neurontin) 300mg; melatonin 0.3mg. PRN: diazepam (Valium) 2.5-5mg.


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poster:Brainbeard thread:948688
URL: http://www.dr-bob.org/babble/neuro/20100223/msgs/949279.html