Posted by Brainbeard on May 29, 2010, at 7:37:55
In reply to Re: 5HT2A-antagonism + 5HT2C-agonism Would Be Ideal, posted by CrAzYmEd on May 28, 2010, at 15:57:35
> "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."
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> But whats the end result? I dont say there arent any anti dopaminergic propertie's, but its 5HT2C antagonism may counteract any anti dopaminergic activity, so in the end its not anti dopaminergic anymore.
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> Like the study i posted points toward INCREASED dopamine and not reduced.Those studies only show short-term effects. Increase in certain area's of the brain doesn't mean overall increase either.
In fact, 5HT2C-antagonism and SRI are opposing mechanisms. Only in lower doses Prozac's 5HT2C-antagonism may dominate, because of the non-linear dose/response relationship for 5HT2C-antagonism, i.e. only a little is enough for significant effects. On higher (therapeutical) doses however, the benefits of 5HT2C-antagonism will be mostly blown away by indirect 5HT2C-agonism. In accordance with this prediction is the fact that high doses of Prozac are used as an anti-bulimia agent, i.e. to suppress appetite. 5HT2C-antagonism INCREASES appetite, while 5HT2C-agonism suppresses it.
There is a very informative study on the web about Prozac's 5HT2C-antagonism in relation to its SRI here: http://www.pnas.org/content/94/5/2036.full.pdf. Please read the part between starts (***).
A quote: 'So far, the therapeutic effects of fluoxetine have been attributed primarily to its inhibition of 5HT transporters. Interestingly, it has been shown that the therapeutic plasma concentration of fluoxetine is in the micromolar range, and our studies show that, at this concentration range, fluoxetine can potently inhibit the membrane current responses mediated by 5HT2C receptors. Moreover, the affinity of fluoxetine for 5HT2C receptors (Ki 5 65 nM) is close to its affinity for 5HT transporters (Ki 5 33 nM) (29), which is also well below the therapeutic plasma concentration of fluoxetine. Thus, some therapeutic effects of fluoxetine may be a consequence of blocking both 5HT transporters and 5HT2C receptors. ***It should be noted that the blockage of 5HT transporters and that of 5HT2C receptors would have opposing actions on serotonergic synaptic transmission.*** (.....) Because of the highly nonlinear dose/response relationship of 5HT2C receptors the blockage of even a small number of receptors in a cell would lead to very profound changes (.....)'.
You seem to jump to overstatements like 'its 5HT2C antagonism may counteract any anti dopaminergic activity, so in the end its not anti dopaminergic anymore.' That's about as unfounded a prediction as saying that lisuride's 5HT1A-agonism will completely counter its anxiogenic properties. Lisuride probably fosters OCD.
If you look at this interesting study on lisuride that I found on Erowid: http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=3705; you see that lisuride induced stereotypical behaviour in rats as well as intensive mounting, i.e. male sexual behaviour. Stereotypical behaviour indicates the potential to exacerbate or induce obsessive compulsive behaviour. And increased libido is not always fun, althoug the accompanying photo of one female rat mounting the other is rather funny.
Anyhow, 5HT2A-agonism inhibits the benefits of both 5HT1A- and 5HT2C-agonism. That's a clinical finding. So if you want to simplify it into good guy vs. bad guy terminology, lisuride does have a bad guy on board, and it's called 5HT2A-agonism. No matter what good things 5HT2A-agonism may do on its own, it's bad news for 5HT1A- and 5HT2C-agonism.
Current meds: 10mg melitracene + 0.5mg flupentixol; sertraline 100mg; amitriptyline 25mg; gabapentin (Neurontin) 300mg; melatonin 0.3mg. PRN: diazepam (Valium) 2.5-5mg.
poster:Brainbeard
thread:948688
URL: http://www.dr-bob.org/babble/neuro/20100223/msgs/949369.html