58 replies to this topic

[Mr. Pink]

 

Hits too many receptors and causes too many side effects. With Eplivanserin i get practically no side effects. It's selective to the 5ht2a receptor. Other than that crypto does look like it might help with sleep. . . but at what cost

I don't know, personally nothing makes me as dull and depressed as 5ht2a antagonism.
Have you tried diphenhydramine and high dose magnesium btw?

 

 

can you tell me more about this. i have atypical depression, and melatonin can make me very depressed and I never knew why. What other supplements should I look out for? Also, knowing this, what supplements should I take?

[adamh]

I was really tempted to try to get some but it has not been approved in any country even after all this time. This leads me to believe it must have some serious side effect or they would have tried harder to get it approved. We don't know if diverculitis was the only side effect. That is serious enough, only 1% perhaps but how long was the trial? If this works I would be taking it for a long time and the risk may go up over long use. The developer must have figured there was no way it would be approved. Insomnia is such a common problem they would have made a major killing if it worked right. To me its just an interesting rc at this point. Let others be the guinea pigs.

[gsubmunu]

Hi,

 

What was your source for Eplivanserin? It looks exceptionally promising as a sleep aid / cognitive enhancer. Might even work as the cure for 5-ht2a receptor mutations like

 

http://www.ncbi.nlm....pubmed/15496511

[protoject]

I was really tempted to try to get some but it has not been approved in any country even after all this time. This leads me to believe it must have some serious side effect or they would have tried harder to get it approved. We don't know if diverculitis was the only side effect. That is serious enough, only 1% perhaps but how long was the trial? If this works I would be taking it for a long time and the risk may go up over long use. The developer must have figured there was no way it would be approved. Insomnia is such a common problem they would have made a major killing if it worked right. To me its just an interesting rc at this point. Let others be the guinea pigs.

 

Hey AdamH,

You should take a look at the paper / link I attached, it will give a better idea of the potential side effects. Mostly they are benign at best, except for that diverticulitis risk, which adds to the risk:benefit ratio. Regardless of whether or not this risk is actually important (it might be, but I'm not sure, for reasons I listed earlier), I've not read about the same issue popping up for Nelotanserin, which works similarly and possibly better. I know there are other ones out there too such as volinanserin, pimavanserin, puvanserin etc so it's always good to look into those as well. That all being said, we can't really be sure why the study with eplivanserin was discontinued. For example, they just simply may have not had enough money to continue studying this when there were better compounds already being developed. Or maybe there was a specific aim of the studies and they were not able to accomplish what they wanted to accomplish. Maybe improving SWS wasn't really a selling point for this drug since consumers want something that's more immediately sedating, and they needed to see a market for it. I'm not really sure, I'm just speculating.

Hi,

 

What was your source for Eplivanserin? It looks exceptionally promising as a sleep aid / cognitive enhancer. Might even work as the cure for 5-ht2a receptor mutations like

 

http://www.ncbi.nlm....pubmed/15496511

 

We have a member of this forum who has offered to have my source's eplivanserin and ritanserin tested for impurities. I wouldn't want people buying this and it containing some sort of harmful impurity. My source was very cheap. In the meantime T&W seems reliable in terms of quality and service and they sell it at a very high price.

[adamh]

 

I was really tempted to try to get some but it has not been approved in any country even after all this time. This leads me to believe it must have some serious side effect or they would have tried harder to get it approved. We don't know if diverculitis was the only side effect. That is serious enough, only 1% perhaps but how long was the trial? If this works I would be taking it for a long time and the risk may go up over long use. The developer must have figured there was no way it would be approved. Insomnia is such a common problem they would have made a major killing if it worked right. To me its just an interesting rc at this point. Let others be the guinea pigs.

 

Hey AdamH,

You should take a look at the paper / link I attached, it will give a better idea of the potential side effects. Mostly they are benign at best, except for that diverticulitis risk, which adds to the risk:benefit ratio. Regardless of whether or not this risk is actually important (it might be, but I'm not sure, for reasons I listed earlier), I've not read about the same issue popping up for Nelotanserin, which works similarly and possibly better. I know there are other ones out there too such as volinanserin, pimavanserin, puvanserin etc so it's always good to look into those as well. That all being said, we can't really be sure why the study with eplivanserin was discontinued. For example, they just simply may have not had enough money to continue studying this when there were better compounds already being developed. Or maybe there was a specific aim of the studies and they were not able to accomplish what they wanted to accomplish. Maybe improving SWS wasn't really a selling point for this drug since consumers want something that's more immediately sedating, and they needed to see a market for it. I'm not really sure, I'm just speculating.

Hi,

 

What was your source for Eplivanserin? It looks exceptionally promising as a sleep aid / cognitive enhancer. Might even work as the cure for 5-ht2a receptor mutations like

 

http://www.ncbi.nlm....pubmed/15496511

 

We have a member of this forum who has offered to have my source's eplivanserin and ritanserin tested for impurities. I wouldn't want people buying this and it containing some sort of harmful impurity. My source was very cheap. In the meantime T&W seems reliable in terms of quality and service and they sell it at a very high price.

 

You mention Nelotanserin but that is an antipsychotic and they say it does not have sedation side effects. I don't see what good it would do for insomnia.

 

"we can't really be sure why the study with eplivanserin was discontinued. For example, they just simply may have not had enough money to continue studying this when there were better compounds already being developed."

 

Drug companies are flush with cash. They could have sold it to another company if it had potential. There are billions to be made with a cure for insomnia, many billions. It doesn't even have to be a cure, just treat the symptoms and be tolerable in the long run. You don't walk away from a jackpot like that without some very very good reasons.

 

"In the meantime T&W seems reliable in terms of quality and service and they sell it at a very high price."

 

Who are t+w, please? I've seen places asking ridiculous prices like hundreds of dollars for a milligram of many that you need many milligrams for. That is not a viable option. I'm beginning to suspect there will never be a cure.

[joenarcoleptic]

I was wondering where you found the Ritanserin.  I have seen it several places, but ultimately comes down to a 'sleep habit' costing somewhere between 10 and 30 dollars a night if it does work.  Was it more affordable than that where you were able to track it down?

[protoject]

 

You mention Nelotanserin but that is an antipsychotic and they say it does not have sedation side effects. I don't see what good it would do for insomnia.

 

"we can't really be sure why the study with eplivanserin was discontinued. For example, they just simply may have not had enough money to continue studying this when there were better compounds already being developed."

 

Drug companies are flush with cash. They could have sold it to another company if it had potential. There are billions to be made with a cure for insomnia, many billions. It doesn't even have to be a cure, just treat the symptoms and be tolerable in the long run. You don't walk away from a jackpot like that without some very very good reasons.

 

"In the meantime T&W seems reliable in terms of quality and service and they sell it at a very high price."

 

Who are t+w, please? I've seen places asking ridiculous prices like hundreds of dollars for a milligram of many that you need many milligrams for. That is not a viable option. I'm beginning to suspect there will never be a cure.

 

Adamh,
It does have effects on sleep. For example:

"In healthy human volunteers, nelotanserin was rapidly absorbed after oral administration and achieved maximum concentrations 1 h later. EEG effects occurred within 2 to 4 h after dosing, and were consistent with vigilance-lowering. A dose response of nelotanserin was assessed in a postnap insomnia model in healthy subjects. All doses (up to 40 mg) of nelotanserin significantly improved measures of sleep consolidation, including decreases in the number of stage shifts, number of awakenings after sleep onset, microarousal index, and number of sleep bouts, concomitant with increases in sleep bout duration. Nelotanserin did not affect total sleep time, or sleep onset latency. Furthermore, subjective pharmacodynamic effects observed the morning after dosing were minimal and had no functional consequences on psychomotor skills or memory. These studies point to an efficacy and safety profile for nelotanserin that might be ideally suited for the treatment of sleep maintenance insomnias."

In terms of why eplivanserin was given up on, I'm not really sure. You'd probably have to talk to the people who were trying to develop it as a medicine. Things aren't always clear cut like that. It doesn't mean you're wrong though, because the robustness of the drug may not have been powerful enough for them to consider it useful. However it did make some significant differences in sleep in the studies, and for me it did as well (using no other meds too). That , to me, hints towards that it does work, because my type of insomnia usually isn't the type to give up.

 

T&W is "Trust and We group" from China, they are a manufacturer /supplier of pharmaceutical goods (nootropics and medications). Their eplivanserin is very expensive, and probably highly pure. I've never purchased it from them. I'm pretty sure the other supplier's eplivanserin is of questionable purity, though much cheaper. As I said before , a member here is having it and ritanserin HPLC tested for impurity and to verify the drug is present. (i subjectively know it's present because it worked in the expected way [and my disorder is highly impenetrable to placebo], but I don't know if an impurity was present. foolish on my part, but desperation).

 

I was wondering where you found the Ritanserin.  I have seen it several places, but ultimately comes down to a 'sleep habit' costing somewhere between 10 and 30 dollars a night if it does work.  Was it more affordable than that where you were able to track it down?

 

You will want to make sure it's a reputable supplier. I got it from China.

[joenarcoleptic]

Can you tell me how much you paid for the Ritanserin, and the name of your unreputable supplier?  I have friends in China that can do a little reasearch for me on whether or not there is a better place to get it over there.

[protoject]

Can you tell me how much you paid for the Ritanserin, and the name of your unreputable supplier?  I have friends in China that can do a little reasearch for me on whether or not there is a better place to get it over there.

 

Hey Joenarcoleptic,

Thanks for the response.

It's great to hear your news.

The NMR results are in from (username hidden until he agrees to me posting his name). it appears that both the ritanserin and eplivanserin i received from the supplier was not legitimate.

(username) told me the results indicated 97% purity but that the product in question was not present. He also indicated that both samples were the same substance, unless there was a human error during testing (i.e. dipping twice into the same bag. they both look the same). He also compared the result to what should show up for other -anserin drugs and found no match.

 

This is disappointing to me because it indicates that my effects were likely placebo.
The strange thing is, that both of the substances produced different effects for me overall, but the same beneficial effect on sleep, which is kind of confusing.

essentially both improved my sleep without being sedating , except the ritanserin lasted all day and amped up my anxiety (felt dopaminergic in a bad way).

So it is indeed very confusing that supposedly they are not even the product in question!!!! ugh. upsetting.

 

Anyway, the supplier was Hangzhou Zenghan Biological Technology Co, Ltd., found on alibaba last year.

They are still there.

 

I was wondering if anyone experienced in chemistry could help analyze the NMR result.

 

I have no idea how NMR actually works and I would like to find out WHAT compound the supplier sent me.

 

 

I've attached the NMR results in PDF form.

 

In the mean time I hope we can find a much better, reputable supplier, who sends us the actual product, and hopefully something that is a viable economically.

 

If not I might take the plunge later on with T&W. but i'd rather not

 

Attached Files

•  NMR_Spectrum_Eplivanserin.pdf   101.16KB   4 downloads
•  NMR_spectrum_Ritanserin.pdf   102.6KB   7 downloads

[protoject]

Id like to apologize for any disappointment I've caused (I'm Canadian, that's what we do, apologize all the time!!!!) but I do hope that this stimulates interest and it ends up benefitting someone in the end.

 

[Flex]

The tricyclic antidepressants have 5ht2a antagonism, some more selective and with high affinity than others.

Doxepin, an old tricyclic antidepressant, has recently been approved in low-dose (3mg and 6mg) form as a sleep aid under the name "Silenor." It's expensive and many people believe the much cheaper, but slightly higher dose generic doxepin is potentially as good. It hits histamine and 5ht2A receptors amongst others. It is indicated for sleep maintenance, rather than sleep initiation and does, I believe, increase slow wave/deep sleep.

Amitryptiline is another tricyclic antidepressant that is used for insomnia and hits ht2A. My concern with this is that a human study has shown the major metabolite, nortriptiline, may be carcinogenic, so I would avoid it.

Mirtazipine has, from memory, high affinity selectivity for mainly just the histamine and 5ht2A receptors, as an antagnoist. However, my understanding is that it has tested positive as a carcinogen in both mice and rats, so my personal opinion is to avoid it.

Cyclobenzaprine, a muscle relaxant / antispasmodic also hits 5HT2A. It is being prepared for "repurposing"(ie seeking regulatory approval for a new indication) as a fibromyalgia treatment (some evidence suggests fibromyalgia may be causatively linked to issue with slow wave sleep, and alpha wave intrusions.)

Cyproheptadine has high affinity for histamine and 5ht2A, is extremely cheap and available over the counter in many countries. It is classed as an antihistamine that it shares a lot of similarity with the tricyclic antidepressants. Its so old that it was not subject to rodent carcinogenisis bioassays, as is the norm since the 70's, so its rodent carcinogenic potential is unknown(in so far as I know, though I think it is not genotoxic at least.)

 

Thanks for the Informations. I´m using Mitrazepine since 2 Years and didnt know that it was Carciogenic.

Btw: most Tricyclic have the Issue to affect the Mitorchondria negatively

 

Effect of tricyclic drugs on mitochondrial membrane.

http://www.ncbi.nlm..../pubmed/2931948
 

[joenarcoleptic]

Based on the structure of Ritanserin, the NMR spectrum should be like the attached image, generated from here:

http://www.nmrdb.org...cc1)c1ccc(F)cc1

(Turns out you can't actually attach an image that is 19200x14400 pixels as a png, and it's too big as any other format)

 

Is there any way to get a higher resolution version of the report you posted in PDF form?

Edited by joenarcoleptic, 24 July 2014 - 11:33 PM.

[joenarcoleptic]

protoject:

 

Did you consider sending your china source a copy of the report and asking them what the deal is?

[Shamanist]

There is also the problem of getting inaccurate NMR results. A quick search of "lab fraud" will show the scope of the problem. It would be great if members posted labs that were bad/good. Thanks Protoject for the feedback on Hangzhou Zenghan Biological Technology Co, Ltd.

 

More on topic is that I find an improvement in sleep quality taking B Complex. If I need to get by with less sleep, then L Tyrosine at bed time has been good. However, some people feel more energetic from B Complex and L Tyrosine, and it makes their insomnia worse.

 

Melatonin helps me get to sleep, but then it causes me to sleep too much. Also, I don't feel refreshed from Melatonin induced sleep. However, it's useful to resetting circadian rhythms.

 

I'd love to hear if anyone has found something as effective as Melatonin. For some, L Tryptophan is a good substitute for Melatonin. Unfortunately, it hasn't helped my sleep, although it does seem to improve my mood if I take it during the day.

 

 

 

 

 

[AustinNotBoston]

i am very interested in 5ht2-a inverse agonists after reading about pimavanserin. I am wondering where you found a supply of eplivanserin. The places I have seen it-and pimavanserin also-charge incredibly high prices. A month's worth would be thousands of dollars.

[protoject]

T&W offered to get me 1 gram for $2500 . . .

I'm working again so i see this as a possibility in the future. However, it is pricy, I'm wondering if I can get a smaller quantity, and, I'm also hesitant to order because the CBSA (canadian border services agency) routinely stops my package, cuts them open, sometimes detains them or sends them back to the supplier.. that's not a $2500 I can waste.

If a few people pitched in though, there could be a good 100 doses in there, even 1000, depending on how much is needed to get the effect.

I was wondering if anyone would bother reading the report i posted earlier so that we could get a better idea of the risks. I've stated what I believe to be the risks based on what I read, but I'm sure there must be someone here smarter than I am who would be able to concur with what I said, or disagree..

[Mind_Paralysis]

I'm going through the BEAST that is unrestive sleep right now, and jesus... I could really use something like this.

 

As of right now, the only alternatives are friggin' Gabapentin and Pregabalin - all other compounds showing vast affinity for a mass of receptors - everything else is really dirty.

 

Alas, both of the two gabapentinoids above are not exactly side-effects free either... I can't take much more of this sleep-deprivation though.

 

 

Sleep-deprivation is holding back my healing of burnout-syndrome, and if I can't fix this, I will never achieve remission... sonuvabitch! *head-bash*

[ISayLonger]

Was any progress on sourcing any of the -anserin's made?

[ISayLonger]

For those still interested, your best alternative to Ritanserin/Ketanserin are non-selective 5-HT2a antagonists, but with very high preference for 5-HT2a.

 

Ziprasidone binds to 5-HT2a ~40x times more than D2, but also antagonises 5-HT2c strongly (which I've found too stimulating). 10mg is too stimulating, 20mg+ the D2 antagonism overrides that, but the D2 antagonism has problems.

 

Risperidone binds to 5-HT2a ~30x times more than D2, but mainly metabolises to Paliperidone which gives it a high half-life at a less optimal binding profile (if you potently inhibit CYP3A4, you could keep mainly Risperidone in your system for sleep duration). 0.25mg works, but it's not very potent. Higher works better but then D2 becomes a problem.

 

Pipamperone is what you really want. A hidden gem, the original Ritanserin derivative, never marketed in the US/written out of history, but is the second most prescribed anti-psychotic in Germany. It's 78x more potent for 5-HT2a than D2, and only other significant activity is D4 antagonism, which isn't as problematic (doesn't cause high prolactin or motor side effects). It's prescribed most often for anxiety/sleep and autism disturbances. 5->15mg.

Be well.

Edited by ISayLonger, 26 March 2018 - 01:46 PM.

[Mind_Paralysis]

In case anyone's wondering, Gabapentin did indeed help with recuperation, and has shown effects on my unrestful sleep - it's helped me a lot, but the issue of tolerance and side-effects such as cognitive dulling, and depression, are very real.

 

 

For those still interested, your best alternative to Ritanserin/Ketanserin are non-selective 5-HT2a antagonists, but with very high preference for 5-HT2a.

 

Ziprasidone binds to 5-HT2a ~40x times more than D2, but also antagonises 5-HT2c strongly (which I've found too stimulating). 10mg is too stimulating, 20mg+ the D2 antagonism overrides that, but the D2 antagonism has problems.

 

Risperidone binds to 5-HT2a ~30x times more than D2, but mainly metabolises to Paliperidone which gives it a high half-life at a less optimal binding profile (if you potently inhibit CYP3A4, you could keep mainly Risperidone in your system for sleep duration). 0.25mg works, but it's not very potent. Higher works better but then D2 becomes a problem.

 

Pipamperone is what you really want. A hidden gem, the original Ritanserin derivative, never marketed in the US/written out of history, but is the second most prescribed anti-psychotic in Germany. It's 78x more potent for 5-HT2a than D2, and only other significant activity is D4 antagonism, which isn't as problematic (doesn't cause high prolactin or motor side effects). It's prescribed most often for anxiety/sleep and autism disturbances. 5->15mg.

Be well.

 

If you're an ADHD-er, or an SCT-er, it's going to be a problem... the evidence is conflicting, but there is some evidence that malfunctioning D4-receptors are the cause of inattention in some such disorders. There's even theories and animal testing going on for creating D4-agonists precisely to treat ADHD, without any of the side-effects of other D-agonists.

 

What's the half-life of Pipamperone? If it's only 8 or so hours, it might not be a problem. (D4 is notoriously curious in that it's the D-receptor least susceptible to up or down-regulation - hence why the focus-enhancing effects of drugs like Amphetamine is the last one to gain tolerance.)

 

Of course, since the majority of peeps DON'T have this issue, then I would agree that Pipamperone looks quite good.

Edited by Stinkorninjor, 26 March 2018 - 02:05 PM.

[ISayLonger]

D4 antagonism, if anything, would up-regulate D4 potentially improving ADHD symptoms (in the day, when taken at night).
Half-life is 26+ in slow metabolisers, 10 in normal. Could be adjusted with enzyme inducers if ADHD is present/timing is key.

[Mind_Paralysis]

D4 antagonism, if anything, would up-regulate D4 potentially improving ADHD symptoms (in the day, when taken at night).
Half-life is 26+ in slow metabolisers, 10 in normal. Could be adjusted with enzyme inducers if ADHD is present/timing is key.

 

Seeing as I myself am a slow metaboliser of CYP2D6 and CYP3A4, then yeah, it might be an issue.

 

The D4-receptor does not upregulate - it does not downregulate much either - it has unique properties differing it from other D-receptors. (this is one of the reasons why D4-agonists have been researched as treatment of negative symptoms in Schizophrenia as well)
 

Of course, it all depends on the dosing... if a very low dose of Pipamperone is all that is needed, then there won't be any D4-antagonism to any noticeable extent.

And as previously noted, only a select few of the various people taking the drug will have that issue.

[Lifemap]

The only thing that I've found to help with insomnia that doesn't leave me groggy in the morning ( sometimes all the way into the afternoon)

Sleep hygiene :

Exercise during the day, no blue light 2 hours before sleep or caffeine 7 hours before bed. Keeping the same wake time  no matter when going to bed, using 10k flux first thing when waking up for 30 min. Also not laying in bed for longer than an hour if I can't sleep, I'll get up read for a bit and try again. Only use bed for sleeping, keep it at a comfortable 68-72 degrees. And lastly guide meditation.

As far as supplements go that don't cause hang over or side effects for me are magnesium, inositol, b6, l-theanine and some herbal tea. Sometimes I will add promethazine( however for some this can make you slightly groggy In the morning) 

 

 I've stuggled with insomnia most of my life.I could get to sleep in about 30-45 min using this regimen, w/o I was averaging 1.5.3 hours to fall asleep. This still wasn't good enough, or I believed there had to be something better out there, after using a CES machine with limited successI finally stumbled across  a product called Nexalin, . I had reservation, and was skeptical of there claims yet when I saw they were running a special  I decided to jump on it .

After my 3rd treatment I fell asleep in under 5 min that night, and this continued for almost 3 months until an injury and depression returned.  I wish there was a cheaper option, something I could purchase to do in my own home as effective as Nexilin or even in-between that and CES.  Or someone was doing Nexalin treatments near me( I had to drive 3 hours to receive treatments) ]

 

However this was by a miracle mile the most effective and bonus non drug/supplemental approach I know of. Truly for the first time in over 8 years I could lay down and be asleep before I even had the opportunity to think why am I still awake. However it wasn't terminate,  like I said it seemed after injury/disease, change in medication and sporadic sleep patterns due to pain, insomnia slowly crept  back in. I believe If this wasn't the case I very well would of for the first time in my life slept normal.  

Edited by Lifemap, 07 April 2018 - 03:42 AM.

[protoject]

I'm going through the BEAST that is unrestive sleep right now, and jesus... I could really use something like this.

 

As of right now, the only alternatives are friggin' Gabapentin and Pregabalin - all other compounds showing vast affinity for a mass of receptors - everything else is really dirty.

 

Alas, both of the two gabapentinoids above are not exactly side-effects free either... I can't take much more of this sleep-deprivation though.

 

 

Sleep-deprivation is holding back my healing of burnout-syndrome, and if I can't fix this, I will never achieve remission... sonuvabitch! *head-bash*

Hey Mind Paralysis,

(a heads up to other readers: my response below is me going on a tangent about my effective insomnia treatment that does not involve the previously discussed 5Ht2a antagonists; a tangent which I intend to follow up perhaps in a brand new thread. If you came here to read strictly about the topic of this current thread, maybe skip this and if you're interested in my detailed experience in treating my own insomnia, keep track of this thread/ follow it, / PM me if interested.  and I will eventually add a link for reference and PM you if I do generate that thread,  detailing the therapeutic experience further). 

Sorry for the late reply, I have not been super active on longecity, but I saw your response and wanted to let you know that in my experience, while the gabapentinoids Gabapentin and Pregabalin may have given you too many side effects, that there is hope that either could still work for you. The reason I believe this is because I have personally experimented and found that, Pregabalin (gabapentin sucks, pregabalin is way  better IMO), and , Trazodone , by themselves, for me, were not achieving the desired effect and, in the case where it was very effective (which I'll explain in a minute), it did have those side effects that I really hated such as : pregabalin:  becoming stupid and emotionally blunted., trazodone: becoming stoned (with higher doses at least which were required at that time without a backup plan) and a terrible mood swing on the withdrawal. 

That being said, I found that COMBINING trazodone and pregabalin (at the lowest possible effective doses , which will vary from individual to individual) gives a TOTALLY MORE EFFECTIVE therepeutic response than either alone. In fact, when i took trazodone alone, it was ridiculous because I'd sleep for 1-2 hours and have to pop another one, so basically it was a shitty sleep candy that barely worked. With Pregabalin, it worked very well at first but I was dosing really high and getting the beneficial effect hours later, and using daily, which caused shitty side effects. 

 

I quit the pregabalin, then later re-implemented lower dosing WITH trazodone, daily, and it remedied my sleep situation enough to make tangible improvements to my health.  However, daily dosing caused those stupid side effects that I hate. Eventually, I quit, and again started up, but this time i did them together on ALTERNATING DAYS instead of daily. This massively reduced their side effects, because taken daily it seems to whittle away at our brains, while taken on alternating days greatly improves side effects and also tolerance and dependence. That being said,  on the alternate day off, I use medications that have different pharmacological effects , whose effects are also improved being on alternating days. Maybe I will create a new post detailing my success and experimentation (which was far better than than eplivanserin, though, i definitely DON'T want to throw out the plausibility of 5Ht2A antagonist drugs as potential therepeutic agents that will likely work, perhaps by themselves or perhaps in combination with something else). 

[grubbo]

Hi there, extremely interesting thread.

 

I'm more interested in it out of a goal to upregulate my 5HT2A receptors, as along with reserpine and perhaps SJW (which I tried for some weeks without notable effect) this seems the only drug that will do that. I am a chronic insomnia victim too however...

 

I just wondered if you're still taking it or had a source for it. The T&W you mentioned in your posts I cannot seem to find. Nobody on alibaba is advertising it, although some are on chemicalbook. Needless to say I'm very wary about quality and would probably want to pay for some independent testing, but I've never done anything like this before...

 

As I think you point out in one of your posts, the 5HT2A complex has this very paradoxical effect where even very structurally similar compounds with basically identical affinities will do quite different things. So ketanserin downregulates (surprised me because it's also a VMAT2 inhibitor like reserpine), pimavanserin brings about no change, and eplivanserin upregulates!

[protoject]

FOLLOW UP

 

 

Hey Mind Paralysis,

This is another follow-up to my last response to you. I wanted you to know I found something else out too,and I think it could be owed simply due to either the a) alternative dosing or b) my body has changed over time so reacts differently somehow.

But recently I ran out of pregabalin, my trazodone stores are low, so I switched back to gabapentin hesitantly. (again, alternative day dosing). This time, i took it without Trazodone. Funnily enough, it actually worked way better than the trazodone and pregabalin. Wierd. i didn't expect it because Pregabalin and Gabapentin almost do the same thing. (well, they do do the same thing, albeit maybe differently). I still got side effects from Gabapentin, like headaches the next day or bloodshot eyes, but otherwise it was actually pretty good.

 

I do think the alternative day dosing must be a factor, because before when I hated gabapentin, i was using it daily. It was wierd when i switched back to my usual Pregabalin the other day, without trazodone, and it barely worked (worked but i kept waking up frequently). 

So if you do ever decide to revisit these meds, or med combos, or whatever, I wouldn't throw even gabapentin entirely out of the picture as it seems it has somehow now worked for me even better than it ever has (except for those first few times of course). In fact I almost want to switch to Gabapentin and just stop bothering with trazodone and pregabalin. I don't know though, I like keeping things in stock in case something fucks up. (if I didn't, i wouldn't have had the good experience with gabapentin, which before I thought was garbage or like, "the worse evil" of gapapentin and pregabalin. 

 

[lrdmelchett]

I'm looking in to the 5HT2a angle myself.  I have some experience with TCAs and 'dirtier' drugs - while somewhat helpful for sleep, ultimately intolerable side effects due to extraneous receptor effects.

 

Trying to decide on Ritanserin or Pipamperone.  Both are good candidates, but with two drawbacks.  1)  Half lives are 20-40 hours!!  2)  Both promote next-day grogginess (see below).   I've gone through the process of giving up Trazodone, Doxepin, and a short trial of Seroquel simply due to diminished capacity the next day.  Doxepin was a winner with the least sedation, but what comes with this next day sedation for drugs trialed so far (for me) is a significant degradation of memory formation and recall - and that's a high price to pay indeed.

 

It's tough to sacrifice vigilance during the day for deep sleep.  Once I've selected one of these drugs I may use it sparingly for sleep recharge sessions when the fatigue gets dire.  It is true that 5HT2a antagonism (see below) extends slow wave sleep by 20-30% - the thinking being sleep efficiency % will go up since waking from deep sleep is physiologically much harder.  I suspect my trials with the TCA's and their effect on memory/cognition might be more closely related to either 5HT2c or anticholinergic effects - I will not know until I try something much more 5HT2a selective.

 

Some references that might be useful:

 

https://innovareacad.../view/8736/5650

able 1: Receptor-binding affinities (expressed as Ki values) of several atypical antipsychotic agents in comparison to haloperidol

 

Clozapine

Olanzapine

Quetiapine

Ziprasidone

Sertindole

Aripiprazol

Asenapine

Risperidon

Paliperidon

Pipamperon

Ritanserin

Haloperidol

...

 

Effect on atypical antiphsychotics on SWS (Very good table on sleep metrics including next day vigilance - it may be possible to find some middle ground dosage between maximizing SWS and minimizing next day reduced capacity)

https://bpspubs.onli....1991.tb05514.x

Edited by lrdmelchett, 07 October 2018 - 12:33 PM.

[jack black]

I'm going through the BEAST that is unrestive sleep right now, and jesus... I could really use something like this.

 

As of right now, the only alternatives are friggin' Gabapentin and Pregabalin - all other compounds showing vast affinity for a mass of receptors - everything else is really dirty.

 

Alas, both of the two gabapentinoids above are not exactly side-effects free either... I can't take much more of this sleep-deprivation though.

 

 

Sleep-deprivation is holding back my healing of burnout-syndrome, and if I can't fix this, I will never achieve remission... sonuvabitch! *head-bash*

 

Hi,

Have you figured out anything helpful for your sleep? My friend from Europe is asking for a recommendation for his sleep problems. He works shifts and can only sleep couple of hrs a day/night and is chronically tired/depressed.  Is Ambien (zolpidem) available in Europe? I know someone in my family who takes it (low, half dose) and swears by it, even though it's very short acting.

Edited by jack black, 08 October 2018 - 04:56 PM.

[Mind_Paralysis]

Hey Mind Paralysis,

This is another follow-up to my last response to you. I wanted you to know I found something else out too,and I think it could be owed simply due to either the a) alternative dosing or b) my body has changed over time so reacts differently somehow.

But recently I ran out of pregabalin, my trazodone stores are low, so I switched back to gabapentin hesitantly. (again, alternative day dosing). This time, i took it without Trazodone. Funnily enough, it actually worked way better than the trazodone and pregabalin. Wierd. i didn't expect it because Pregabalin and Gabapentin almost do the same thing. (well, they do do the same thing, albeit maybe differently). I still got side effects from Gabapentin, like headaches the next day or bloodshot eyes, but otherwise it was actually pretty good.

 

I do think the alternative day dosing must be a factor, because before when I hated gabapentin, i was using it daily. It was wierd when i switched back to my usual Pregabalin the other day, without trazodone, and it barely worked (worked but i kept waking up frequently). 

So if you do ever decide to revisit these meds, or med combos, or whatever, I wouldn't throw even gabapentin entirely out of the picture as it seems it has somehow now worked for me even better than it ever has (except for those first few times of course). In fact I almost want to switch to Gabapentin and just stop bothering with trazodone and pregabalin. I don't know though, I like keeping things in stock in case something fucks up. (if I didn't, i wouldn't have had the good experience with gabapentin, which before I thought was garbage or like, "the worse evil" of gapapentin and pregabalin. 

 

 

Yo man! = ) Cheers for the reply. I tried Gabapentin as well, and actually found it to be fairly effective - it goes a bit back and forth what dosage I use, but in general, I would say it's a keeper for sure.

 

 

I would like to make another professional sleep-study though, to figure out if I truly still have, permanent, PLMD. Different med's and environmental factors seem to trigger it, so I need to redo the testing completely medication-free.

 

Until then, I seem to do better with a low dose of gabapentin most nights of the week.