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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by Noa on March 11, 2001, at 15:10:21
Does anyone have information on 5HT4 receptors, and antagonists thereof? Thanks.
Posted by SLS on March 12, 2001, at 8:24:07
In reply to Any info on 5HT4 receptors?, posted by Noa on March 11, 2001, at 15:10:21
> Does anyone have information on 5HT4 receptors, and antagonists thereof? Thanks.
I'm curious, Noa. Why the interest?
- Scott
Posted by Noa on March 13, 2001, at 12:05:46
In reply to Re: Any info on 5HT4 receptors?, posted by SLS on March 12, 2001, at 8:24:07
Well, I am researching what I believe is a dose-related side effect of my serotonergic medication---kind of delicate topic, but here goes---bladder problems.
I found some material and wrote to the authors to get more info. I'll let you know if they respond.
Posted by SLS on March 13, 2001, at 16:53:12
In reply to Re: Any info on 5HT4 receptors?, posted by Noa on March 13, 2001, at 12:05:46
Dear Noa,
I took it upon myself to look into 5-HT4 receptors on the day of your post. I was able to find some information regarding their location and function. They seem to help regulate peripheral smooth muscle contractility, including cardiac and gastrointestinal. These receptors are also present in the human bladder. Stimulation of 5-HT4 receptors will decrease bladder capacity by preventing its relaxation during filling. This seems to be mediated via the ability of 5-HT4 receptors to increase the release of acetylcholine, the neurotransmitter responsible for muscle contraction. I don't know how Serzone, Effexor, or the SSRIs would affect the stimulation of these receptors, but if they do, reduced bladder capacity would be the result.
One of my thoughts is that it might be the Serzone you take that is the culprit. One of its metabolites, mCPP, is a potent 5-HT receptor agonist, precisely the type of agent capable of reducing bladder capacity. Unfortunately, I could not find any investigations studying this issue. It's just a less than educated guess.
I also came upon an abstract that described a role for 5-HT1a receptors on bladder capacity, but I don't remember if they were located within the bladder or in the CNS.
Thanks for teaching me something new! :-)
- Scott
Posted by Noa on March 13, 2001, at 17:09:40
In reply to Re: Any info on 5HT4 receptors?, posted by SLS on March 13, 2001, at 16:53:12
Scott, thank you for looking up the info and explaining it to me.
So you think it is the serzone, while I think it is the venlafaxine, although I am almost afraid to say that here, because it has been getting such a bad rap here these days,and despite the unwanted effects like this one, I think it is a pretty good medication.
Here is a letter I emailed to the author of one of the articles I found on the subject:
Dear Dr. Zorn,
I read with interest your July, 1999, report in Journal of Urology on your findings of a correlation between depression and urge incontinence.
I am treated for depression and hypothyroid with a cocktail of medications that includes the antidepressants venlafaxine (xr) and nefazodone. My experience is that my urge incontinence began *after* initiation of treatment with venlafaxine, particularly after attaining a dose level above 225 mg.
Your article indicates that there was a higher incidence of urge incontinence among patients with a history of treatment for depression, and who scored higher on the Beck, but I did not see any reference to controlling for whether these patients with depression were taking any antidepressants, and wonder if this is something you might have considered, either at the time of your research or since then.
Although there might be a relationship between deficiency in serotonin function and urge incontinence, it has been my "hunch", as a layperson struggling with this problem, that serotonergic antidepressants overstimulate the serotonin receptors in the bladder or ureter (or both). In fact, I have also found support for this idea from the literature.
I recently came across an article by Votolato, et. al. (Serotonergic antidepressants and urinary incontinence.Int Urogynecol J Pelvic Floor Dysfunct 2000 Dec;11(6):386-8), which suggests that activation of the 5HT4 receptors on the bladder might be the mechanism connecting serotonergic antidepressants and urge incontinence.
The role of 5HT receptors in ureter contractions is also discussed by Gidener, et.al. in Urol Int (1995;55(4):202-4), "Influence of serotonin on the human ureter: an in vitro pharmacological study."
Another study suggesting that serotonin could activate the urinary tract is "Effects of drugs on the upper urinary tract of the human" (Urologe A 1986 Sep;25(5):252-8, Hertle and Nawrath). They found that both norepinephrine and serotonin had excitatory effects on the muscle tissue of the ureter.
Similarly, Long and Nergardh, in their study, "Autonomic receptor functions of the human ureter: an in vitro study"(AScand J Urol Nephrol 1978;12(1):23-6), found that "a dose-dependent, reproducible, contraction response to 5-hydroxytryptamine (Serotonin, 5-HT) was demonstrated....This suggests that contraction of ureteral smooth muscle is mediated through receptors which are sensitive to 5-hydroxytryptamine."
My experience has been that the problems I have had with urge incontinence during my waking hours are not present at night. Although I might wake up once during the night to void, it is very rare that the urge feels so compelling that I feel at risk of losing control before reaching the bathroom, whereas this is a common occurrence for me during the daytime. My suspicion is that this is because of the 5HT antagonist effects of the nefazodone, which I take in one dose (350 mg) about 1-3 hours before bedtime. Nefazodone was added to my medication cocktail because of the 5HT2 antagonist effects, to counter the overactivation I have experienced from the venlafaxine (insomnia, restlessness, fidgitiness, restless legs, myoclonus, etc.). I suspect that nefazodone also has some role in reducing my urge incontinence at night, perhaps by inhibiting the excitatory effects of the venlafaxine on the ureter and/or bladder.
I am most interested to hear your response to my comments and to find out if you have considered the issue of serotonergic medications in your finding of a higher incidence of urge incontinence in people with depression, and whether you are undertaking any further research on this topic.
Thank you.
Scott--I actually found Dr. Zorn's whole article at the public library health section, but the citations of the other research are based on reading abstracts. I wish I had access to more journals, and can't afford to order them through the internet. I guess if I really wanted to I would go to a medical library, but just haven't had the time.
I have been sending my pdoc the references and copies of any emails I send to article authors. I will let you know if any of the researchers respond. What do you the the odds are?
Posted by Noa on March 13, 2001, at 17:13:07
In reply to Re: Any info on 5HT4 receptors?, posted by SLS on March 13, 2001, at 16:53:12
> Scott, thanks for teaching me something new!!!
So it is the acetylcholine that is responsible for the myoclonus, too?
The reason I think the serzone isn't the culprit is that serzone stops muscle contractions like myoclonus, for me anyway.
What do you think?
Posted by Noa on March 13, 2001, at 17:20:23
In reply to Re: Any info on 5HT4 receptors?, posted by SLS on March 13, 2001, at 16:53:12
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2604003&dopt=Abstract
Would you mind reading this one and help me understand it? Thanks.
Posted by Noa on March 13, 2001, at 17:35:09
In reply to Re: Any info on 5HT4 receptors?, posted by SLS on March 13, 2001, at 16:53:12
I found this, too.
http://www.tocris.com/serotonin.htm
I guess my next step is to better understand the timing of how nefazodone produces mcPP. Acc. to this articleon 5HT receptors, mcPP disrupts sleep, for example, but 5HT2 antagonists (nefazodone is one) enhance sleep (my experience with it), but I wonder if timing is a factor, if the mcPP is a metabolite of the nefazodone--does this mean it is essentially a breakdown product?
WOuld timing of dosing have an effect on the ratio of nefazodone:mcPP in my system at any one time and could changing the dosing time so that there isn't as much of a fluctuation in this ratio help to reduce the (suspected) effects of the mcPP on the bladder?
Posted by Noa on March 15, 2001, at 16:35:24
In reply to Re: Any info on 5HT4 receptors? » SLS, posted by Noa on March 13, 2001, at 17:35:09
Any input on this?
This is the end of the thread.
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