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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by Sarah T. on March 2, 2005, at 2:37:29
I posted this above but that thread seems to have been swallowed by archiving, so here it is again: Is Prozac the only ssri that antagonizes 5HT2C receptors? I think it was Linkage who said that Prozac is both an agonist and antagonist at the 5HT2C receptor. So, other than Remeron, Trazodone, Prozac (sort of), and some of the atypical AP's, what other meds do this? Oh, I think Serzone might have been mentioned, but isn't that one of the ones that's half and half, like Prozac?
Posted by cache-monkey on March 4, 2005, at 12:43:39
In reply to SSRI's that are also 5HT2C-receptor antagonists?, posted by Sarah T. on March 2, 2005, at 2:37:29
How come the curiousity with the 5-HT2c, in particular?
My experience with the 2c is that antagonists => reduced anxiety, weight increase, decreased sexual function (particularly in males). [I have references to back all of these effects up, if you're interested.]
So, while you might get better anxiolysis with a 2C blocker, I think that's where (for me, at least) the most troublesome side effects come from.
I'm not sure about Serzone's direct effect on the 5-HT2c receptor (I didn't think it had one), but it's metabolite (mCPP) is a strong _agonist_ of that receptor.
In terms of SSRIs, both Celexa and Prozac show strong binding affinities for the 2c receptor. Zoloft seems to be neutral. (http://www.ocfoundation.org/ocf_0030.htm) I don't know anything about the others.
Hope this helps,
cache-monkey> I posted this above but that thread seems to have been swallowed by archiving, so here it is again: Is Prozac the only ssri that antagonizes 5HT2C receptors? I think it was Linkage who said that Prozac is both an agonist and antagonist at the 5HT2C receptor. So, other than Remeron, Trazodone, Prozac (sort of), and some of the atypical AP's, what other meds do this? Oh, I think Serzone might have been mentioned, but isn't that one of the ones that's half and half, like Prozac?
Posted by mbluett on March 5, 2005, at 9:50:29
In reply to SSRI's that are also 5HT2C-receptor antagonists?, posted by Sarah T. on March 2, 2005, at 2:37:29
Prozac is a 5HT2 agonist and causes all the ill effects related to stimulation of this receptor. Those being anxiety, insomnia, anorexia....
Posted by Maxime on March 5, 2005, at 12:42:29
In reply to SSRI's that are also 5HT2C-receptor antagonists?, posted by Sarah T. on March 2, 2005, at 2:37:29
Serzone was taken off the market in Canada and in Australis ( other countries as well????) because it can cause liver damage. If you plan to take make sure you have your liver enzymes tested.
Cheers,
Maxime
Posted by Maxime on March 5, 2005, at 12:43:50
In reply to Re: SSRI's that are also 5HT2C-receptor antagonists?, posted by mbluett on March 5, 2005, at 9:50:29
Ooops, sorry about that typo. AUSTRALIA
Posted by Sarah T. on March 5, 2005, at 20:21:48
In reply to Re: SSRI's that are also 5HT2C-receptor antagonists?, posted by cache-monkey on March 4, 2005, at 12:43:39
Hi Cache-Monkey. I really appreciate your reply. The reason I've been interested in drugs that antagonize this receptor is that I thought I might be able to get some of the benefits of serotonin WITHOUT the apathy and amotivational syndromes that are so common with many ssri's. Celexa was the worst in that respect. A few others were similar in effect but not as deadening as Celexa. Yes, I've read about that m-CPP metabolite of Serzone and Trazodone. If only they'd make Trazadone without that metabolite! Apparently m-CPP also causes INCREASED cortisol levels, which is the last thing I need right now.
Posted by Sarah T. on March 5, 2005, at 20:23:06
In reply to Re: SSRI's that are also 5HT2C-receptor antagonists?, posted by mbluett on March 5, 2005, at 9:50:29
Thanks mbluett. I don't think I'll take Prozac now.
Posted by Sarah T. on March 5, 2005, at 20:25:12
In reply to Re: SSRI's that are also 5HT2C-receptor antagonist, posted by Maxime on March 5, 2005, at 12:43:50
Thanks, Maxime. I'm pretty sure I won't be taking Serzone or Trazodone. Even if Serzone didn't cause those liver problems, both Serzone and Trazodone have a metabolite that causes increased cortisol, which I already have, as well as anxiety in susceptible individuals.
Posted by Maxime on March 6, 2005, at 9:55:59
In reply to Re: SSRI's that are also 5HT2C-receptor antagonists? » cache-monkey, posted by Sarah T. on March 5, 2005, at 20:21:48
>Yes, I've read about that m-CPP metabolite of Serzone and Trazodone. If only they'd make Trazadone without that metabolite! Apparently m-CPP also causes INCREASED cortisol levels, which is the last thing I need right now.
What do increased cortisol levels do? I'm sorry, my brain is not functioning and I can't remember anything right now ....
Maxime
Posted by cache-monkey on March 6, 2005, at 14:33:10
In reply to Re: SSRI's that are also 5HT2C-receptor antagonists? » cache-monkey, posted by Sarah T. on March 5, 2005, at 20:21:48
Hey there,
So, I'm not sure how 5-HT2C relates to apathay/motivation. And Celexa should have been a relatively good 2C antagonist, too... I'm wondering if maybe what you're looking for is a 5-HT2A antagonist. (2A blockade => increased dopamine: see http://www.preskorn.com/columns/9803.html).
Which would make Serzone ideal, except for that pesky mCPP. I was on serzone for about 8 months and it made me really freaked out and anxious (and hypersexual and almost anorexic) the whole time. Based on what I read about mCPP, I think that was the root cause.
My stressed out response was probably a function of my liver chemistry. mCPP is cleared by the liver enzyme CYP-2D6. Based on my response to Serzone, I actually got a genetic test done on my (likely) liver enzyme capacity, and it turns out I'm (probably) pretty deficient in CYP-2D6. As a result I got mCPP overload. (All the parenths to say that these genetic tests only give likelihoods, not necessarily your actual capacity.)
Have you tried Serzone? For most people, I think the mCPP isn't much of an issue, just the poor/intermediate CYP-2D6 metabolizers. You might want to get tested for your 2D6 function, since lots of other antidepressants/psychotropics are metabolized by that enzyme. (A simpler test might be to consider whether a standard dose of nyquil really seems to knock you out for 12+ hours...)
Anyway, good luck with your AD quest.
Peace,
cache-monkey
> Hi Cache-Monkey. I really appreciate your reply. The reason I've been interested in drugs that antagonize this receptor is that I thought I might be able to get some of the benefits of serotonin WITHOUT the apathy and amotivational syndromes that are so common with many ssri's. Celexa was the worst in that respect. A few others were similar in effect but not as deadening as Celexa. Yes, I've read about that m-CPP metabolite of Serzone and Trazodone. If only they'd make Trazadone without that metabolite! Apparently m-CPP also causes INCREASED cortisol levels, which is the last thing I need right now.
Posted by Sarah T. on March 7, 2005, at 21:53:19
In reply to Re: SSRI's that are also 5HT2C-receptor antagonists? » Sarah T., posted by cache-monkey on March 6, 2005, at 14:33:10
Hi. Thanks for the link to Sheldon Preskorn's site. I logged onto that site a few years ago and thought it was so good, and I've been meaning to go back to it ever since.
I might very well be mistaken about the 5HT2C receptor. I thought that those receptors were dense in the frontal or prefrontal lobes, and that when they are antagonised, there wouldn't be such a huge increase in serotonin there, which would mean that there wouldn't be such a large corresponding decrease in dopamine in the same location. I thought that the frontal lobes were very important in motivation, so I don't want to lower dopamine in that part of the brain. I am like a limp rag on Celexa, mentally as well as physically, so I assumed that Celexa must be agonising that receptor.
I also didn't realize that antagonism of that receptor caused increased appetite. I always thought it was one of the histamine receptors that was responsible for that. Perhaps it's both?
I had a paradoxical reaction to Trazodone. It made me anxious and sleepless. That was a huge disappointment for me. I really wanted to take a non-benzodiazapine sleep aid that would have some mild antidepressant efficacy as well. I haven't had those genetic tests yet. I probably will, but I think they will just confirm what has been observed clinically over numerous failed medication trials, especially those involving drug combinations. Wouldn't it be great if we could have custom-made medicines, tailored to suit our individual genes and biochemisty?
Thanks again for your help. By the way, that's a cool screen name, Cache-Monkey!
This is the end of the thread.
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