Posted by Stan on August 7, 2002, at 7:44:30
In reply to Re: Tremendous strides with ondansetron , posted by Shawn. T. on August 7, 2002, at 1:53:40
<<<<<Shawn T. wrote the stuff in brackets>>>>>
<<<<<<Other selective 5-HT3 antagonists are granisetron, tropisetron, and hydrodolasetron. I find tropisetron to be the most interesting one of the bunch (2 to 5mg hint hint). You would probably be able to give the people curious about substance p antagonists a bit of knowledge (5-HT3 antagonists may be better in my opinion, but I can't say for sure). I'd like to hear from someone that has combined one of these drugs with Wellbutrin; I am wondering about how that might work out. Note that I'm primarily interested in these drugs for their pain relieving effects (some people say antidepressants are actually analgesics; I would agree).>>>>>
hi shawn - i haven't tried any of the 5-HT3 antagonists alone or in combination but i'm certainly going to research those links you posted to see if one might be appropriate for experimentaion without costing a fortune like ondanestron. i recall you mentioned that blocking this receptor may inhibit the release of substance P which in turn may result in a reduction in psychic pain as well as physical pain. for some reason i seem to remember hearing some second-hand reports that merck's "substance P" drug trials weren't going very well and perhaps their investigational drug wasn't proving very effective at alleviating depression & anxiety.....but that info could be flawed.
<<<<I disagree with the kitchen sink statement about Remeron; I find that it is a well thought out drug.>>>>>
i was the one that made that statement, but i didn't mean it in a derogatory sense -- in fact it may be the next antidepressant that i try. i think antagonism of 5-HT2A, 5-HT2B, 5-HT2C, and 5HT3 (all of which remeron accomplishes) is capable of producing positive improvements in depressives whose symptoms include anxiety, insomnia, agitation, restlessness, etc. i'm taking serzone, which only antagonizes 5-HT2A, and i'm still highly anxious and wondering if blocking those additional sub-receptor groups with remeron would be more beneficial for me.
however, as far as remeron's effects at adregenic and histamine sites go, i'm not so sure that that the drug scores high marks for minimizing side effects with its various manipulations in those places. it is an alpha-2 antagonist, which is good in the sense that this allows more serotonin to be released (and "directed" towards the 5HT1A receptor) but perhaps not so good from the standpoint of releasing too much NE and perhaps being over-stimulative and actually having an anxiogenic effect for some sensitive patients who are bothered by over-activation. it seems that a VERY potent antihistamine effect (blocking H-1) was thrown in to counterbalance this excess NE release.....and there's the rub. no drug is perfect, of course, but it seems to me that this is where this drug falls down.....it's common for antihistamines to produce sedation and weight gain, and many people become more depressed when they are tired much of the time and if they're already above their ideal weight (very common for americans), additional gains can be equally depressing. histamine blockers can be somewhat anxiolytic and promote sleep, but it appears that remeron's antihistamine effects are just too potent for the average individual. higher doses (45-60 mg) are supposed to activate the NE-releasing effect to such a degree that the antihistamine consequences become less noticable and sedation less pronounced.....but i wonder why the alpha-2 and H-1 antagonism wasn't left out altogether (hence my "kitchen-sink" comment about affecting multiple receptors). but since i've never taken it and because i assume that it's very difficult to "design" these newer drugs to an optimal degree, then i guess we just have to give remeron the benefit of the doubt. i look forward to trying it this fall sometime.
<<<<< What's not well thought out is the dosage recommendations. 7.5mg/day works well for me, and I was even considering lowering the dosage just to see what happens. I burned one of my fingers on a hot oven coil and felt a glimpse of slight pain for about a second. I can bite hard into my arm (for science, not mutilation), leaving a mark, and feel no pain at all. Stubbing my toe isn't nearly as bad as it used to be, etc etc. I'll go deeply into detail on why 5-HT2 and 5-HT3 antagonists relieve pain if anyone wants me to...
Shawn>>>>>i'd be very interested in reading your comments pursuant to that topic, shawn, if you get a chance to post them. also, here's a link to an article that covers certain aspects of remeron which may be of interest to you -- if you scroll down aways you'll see that the author suggests that at low doses, remeron's potent antihistamine properties essentially override its other effects, which he claims kick-in only after doses considered therapeutic for depression are administered (15 mg and higher). by the way, what do you think of serzone? if you haven't tried it, perhaps you'll have comments on a purely theoretical basis. here's that link:
Column - Imipramine, Mirtazapine, and Nefazodone: Multiple Targets:
http://www.preskorn.com/columns/0003.htmlStan
poster:Stan
thread:115356
URL: http://www.dr-bob.org/babble/20020807/msgs/115522.html