• N&PD Moderators: Skorpio | someguyontheinternet

Relative Selectivity of A/Ds for Serotonin Over NA and DA Uptake

One more question about Remeron...Can anyone explain, to the best of their knowledge, what Remeron is actually "doing" in the brain? I heard it inhibits serotonin reuptake yet I've heard it's a serotonin antagonist. I've heard it inhibits norepinephrine reuptake. I've also heard it releases serotonin and/or norepinephrine. I've never heard of it having any effect on dopamine.

So what's the deal, especially concerning inhibition of reuptake and secondly, release, of the "big 3" neurotransmitters, serotonin, norepinephrine, and dopamine? Which does it inhibit reutake up, which does it cause release of, and which is it an antagonist of? Any other details about it's "mechanism of action(s)" is also greatly appreciated. Thanks again.
 
b-adrenoreceptor = the Beta-adrenoreceptor or Beta adrenergic receptor.

I've allready said, the reason why TCAs cause sedation is because of their potent antihistamine effects.

You want a sedative/hypnotic, I recomend the new ones (Zolpidem, zopiclone, zaleplon) definatly not a benzo.

Remeron (mirtazapine) doesn't inhibit the uptake of anything, it's an alpha-2 adrenoreceptor antagonist, and a 5-HT2/3 antagonist... It does increase impulse-mediated (i.e. non-amphetamine like) noradrenaline, and probably serotonin release.
 
Remeron (mirtazapine) doesn't inhibit the uptake of anything, it's an alpha-2 adrenoreceptor antagonist

Does it cause anxiety to any degree, as the commonly cited alpha-2 autoreceptor antagonist is yohimbine, and it can bring a whole load of anxiety with its use. Also is mirtazepine one of the ones that has priapism as a side effect (again via the alpha-2 antagonist activity)
 
*shrug* about side effects, I don't even know the order of potency when it comes to its receptor effects.

Sure I recommend zopiclone over a benzo, benzos have worse trouble with rebound anxiety, dependence and amnesia.
 
BilZ0r, benzos are the only class of drugs that have helped at all with my insomnia...and after a couple MONTHS of taking estazolam, I haven't developed a tolerance although I vary my nightly dosage from .5-4 mg/night and take some, 1 or 2 nights a week, nights off.

I've tried Zolpidem (crapped out after about a week, tried again months later and it did nothing), zaleplon never worked, and I'm waiting for the single isomer of zopiclone (Lunesta) to come out before I try that...bizarelly, my VERY knowledgable psychiatrist hadn't heard of IMOVANE. Are IMOVANE/Lunesta in the same or a similar class of drugs as Ambien and Sonata?

Thanks for the clarification on Remeron. I don't think I'll take it for sleep as adding ANOTHER A/D probably isn't a good idea consider I'm Bipolar. In fact, our (my psychiatrist and I) decided to keep me at 300 mg/day Lamictal but reduce the Cymbalta from 60 to 30 mg/day (slowly over the next 2 weeks). SSRIs have almost always caused some degree of insomnia in me - Paxil being the work but most effective, Lexapro having the least effect on sleep but the least, almost no, antidepressant effect at all. So Cymbalta is probably contributing (who knows to what degree? Rhetorical ?) to my insomnia...plus the SNRI effect could make the insomnia even worse (just a possibility). I'll see what halving the dose does, although I won't know for about a month.
 
Well I would geuss then your problem isn't insomnia, it's anxiety. All of the drugs which didn't work for you are very good sedatives, but they are very poor anxiolytics.

Yes, Sonta (zaleplon) Imovan (Zopiclone) and Ambien (Zolpidem) are all in the same class of non-benzodiazepine GABA-A modulators, more importantly, they are all BZ1 receptor selective (BZ1 = GABA-A complex with Alpha(1) and Gamma(x), and BZ2 = Alpha(2,3,5) Gamma(x))..
 
Last edited:
It's funny that you say my problem is anxiety. About 2 years ago, I started off having panic attacks which I believe pot was a MAJOR contributing factor in. Rx'd Ativan as needed, but as needed quickly went from every 2-3 days to every day, to every few hours and if I wasn't having panic attacks, I was just anxious all the time. I was rediagnosed as having Panic Disorder as well as Generalized Anxiety Disorder. Soon after that, I went on A/Ds and have been on them (many different ones or combination of psychiatric drugs) ever since. Within a month of getting on an A/D, I almost never felt anxious and had no more than 1 panic attack a week. After 2-3 A/Ds and a couple more months, anxiety and panic attacks had disappeared completely...out of fear of them returning, I stayed on whatever A/D I was on at the time, ah it was Celexa. Then I started becoming depressed, increased dose from 40 to 60 mg/day, getting more depressed, 60 to 80 mg/day, more depressed, and eventually so bad I withdrew from school a week before finals and came home to live with my parents till I "got better." Since the depression started (and even in the few months before), I haven't had anxiety or panic attacks AT ALL...when I came home I was rediagnosed as Bipolar and since then I started new treatment and finally feel the best I have in over 2 years (taking 300 mg/day Lamictal, 60 mg/day Cymbalta.).

Basically, I have to disagree with your guess (although logical) that my problem is anxiety. I may not have been extremely accurate in describing the effects of all the various meds I tried for sleep. Some simply didn't work at all, some worked perfectly for awhile then crapped out, some didn't work quite well enough (even at higher doses), and some worked "too well" and I'd sleep for way too long and feel "hungover" when I got up (even at lower doses). So I've had varying degress of "success" with non-bnezo sleep meds, just not great.

I say a benzo would be great b/c of my past experience with them. ProSom just lasts too long really...the fact that it takes awhile to kick in, well, I just offset that by taking it early (between 7-9 PM depending on when I want to fall asleep). I REALLY think the Cymbalta is contributing to the insomnia, as does my doctor, and that's why we halved it to 30 mg/day (slow reduction). Maybe I'll be able to take a lower dose of ProSom then and won't sleep so long then. He rejected my request for temazepam, but he only like to make one change at a time...which can be frustrating, but his reasoning is very sound - if we changed more than one thing and had any effects, good or bad, we wouldn't really know which drug (or dose) change had caused the effect.

I'm thinking next time (appointment, approx. 1 month), I'll either be sleeping better with a lower dose (highly unlikely, but maybe even none) of estazolam and therefore not sleeping too long OR my insomnia won't be as bad, but regardless of dosage, the estazolam will still last too long. I think the latter is more likely. At that point, he'll want to Rx Lunesta...but I'll want to try temazepam. So maybe we'll cut a deal and I can ask for both and just say that I'll play around with his recommended doses of each and see what (if anything) works best. He has let me do similar things in the past so I don't see he wouldn't this time. I may also just ask about taking a high dose of lorazepam for sleep as I've taken it before and it was sedating and didn't least excessively long. I think once I get to 300 and 30 mg/day of Lamictal and Cymbalta respectively, one of the following will "cure" my insomnia: lower dose of estazolam, some dose of temazepam, some dose of Lunesta, or a higher dose than I took in the past of lorazepam (when I took it for panic attacks). After about 2+ years of panic disorder, GAD, depression, insomnia, and Bipolar episodes, I just feel like I'm so damn close to being back to where I was before all this started (I never use the word "normal"). The sleep is the last and final hurdle...almost there.
 
Cymbalta (duloxetine) has very similar affinity for SERT and NET (Ki = 1.3 and 3 nM respectivly). Although I've never seen its DAT affinity reported, we can assume it is negligable as it doesn't cause an increase in extracellular dopamine.
 
In that pamphlet that comes with Cymbalta (and every Rx) that has all the information on the drug (including pictures of the molecule, etc.), it says something like 'It has a potent and similar effect in terms of inhibiting reuptake of both serotonin and norepinephrine. It causes minimal reuptake inhibition of dopamine.' Now that's not the exact quote, just the jist of it (from what I can remember)...I can find the exact quote if anyone wants it, just let me know, although it won't be much different (in terms of meaning anyway) than my fake quote.
 
Top