1 votes
Posted 17 September 2014 - 07:58 PM
I'm more eager for pitolisant if only because I want to see its phase III data related to safety since it is after all the furthest along and potentially first to market of this new class. Even if irdabisant sails through trials it will be many years before it comes to market.
Yeah I hear ya, transhuman techonologies sells it....they are good to go as well.
I would go there rather than investing in a lab or research chem site.
Posted 17 September 2014 - 09:13 PM
What vendor are you using for the conessine? I'm new to this and don't trust suppliers in general - and sigma and the big players cost $$ and I'd need to do a group buy.
I did have a source that was able to get custom synthesis but since have lost that source, so as of late I've just been using the herb "Kutaj" and sometimes shifting to "Yamoa" or using both. Both of which contain conessine.
Posted 17 September 2014 - 09:32 PM
Who are you using as the supplier of those? I'd at least like to use the same supplier that you are, with a lot of these the prep procedures change and so the dosages may be all over the map.
When you say Kutaj do you mean Kutaja?
Posted 17 September 2014 - 09:41 PM
Who are you using as the supplier of those? I'd at least like to use the same supplier that you are, with a lot of these the prep procedures change and so the dosages may be all over the map.
When you say Kutaj do you mean Kutaja?
Personally, you might not wanna use the same supplier I use in terms of raw powder, it tastes nasty as fuck and most people will not be able to handle it. Anyway - it's "Dr.Wakde" natural health clinic for powder..for capsules I use "Morphium" which is from India.
You have to take ALOT of it though.
Kutaj = Hollarhena Antidysenteria = also is a good detoxifier and bowel strengthener.
Can't go wrong with detoxifying, increasing overall health and having the best natural stim on Earth at the same time, imHo. 
Edited by Area-1255, 17 September 2014 - 09:44 PM.
Posted 19 September 2014 - 09:49 PM
Interesting read... Love your blog Area!
Btw, where did you source Conessine?
Sigma back then for the pure kind. Kutaj or Yamoa for herbal.
Morphium sells the capsules, Dr.Wakde sells the powder (Kutaj).
Posted 22 September 2014 - 07:30 PM
What have you seen / tried that are enkephalin modulators? That's a whole area I haven't looked into at all.
Tons of stuff interacts with them, I've never use an enkephalin specific compound, though.
It would seem being that histamine H3 antagonists are known to alleviate pain and depression, as well as cognitive deficits; that enkephalin indirect modulation is at least one of the mechanisms involved.
Look into "Thioperamide". Strong anti-inflammatory, anti-cortisol and yet INCREASES histamine release & turnover.
Posted 27 September 2014 - 01:46 AM
5-HT1A antagonists also increase histamine release....ESPECIALLY those with dual dopamine agonist properties...such as WAY 100,635.
Posted 28 September 2014 - 12:57 AM
High dose pindolol + ropinirole?
That would definitely cause a large histamine release, possibly even a dangerous one. Pindolol's beta blocking property would be my concern. Beta blockade plus dopamine d2 agonism would double the decrease in cyclic AMP and thus cause massive histamine release.
Also beta blockade would upregulate histamine h1 receptors, which imo are not the receptor that most of histamine's benefits come from. Except, vigilance and wakefulness. But general energy production and mood lifting come from the h2r, as well as the vasodilation benefits.
Edited by Area-1255, 28 September 2014 - 12:59 AM.
Posted 29 September 2014 - 12:58 PM
One thing I see, and have experienced, is that both Ache and GABA transaminase inhibition is very synergistic with h3 blockade...which makes sense...
Presynaptic regulation vs reuptake, and it's postulated that reuptake is favorably affected by h3 blockade.
Posted 02 October 2014 - 03:23 PM
And again, I've been on both ends; low and high histamine - either way - and even with anxiety - histamine H3 antagonists helped a lot. When low they helped probably by the overall increase in histamine, when histamine was high it helped, even though histamine was sent even higher - this is because by negative feedback you will a net stabilization in histamine neurons since some of the other receptors besides h3's actually will promote cAMP accumulation leading to ironically, an overall stabilization in mast cells.
Posted 04 October 2014 - 07:37 PM
Posted 04 October 2014 - 08:57 PM
Here is an excellent summary of SIRT1-7 and some info how they deacetylate? core histones.
I haven't looked into it deeply but cant help wondering how this relates to the info here?
http://www.hindawi.c...ar/2011/235754/
Histone's are totally different than histamine's. From what I've read, histamine is essential to the parasympathetic nervous system, and helps keep you in a relaxed state ; even though it can be stimulating - it's 360 degrees different than the stimulating action of adrenaline.
Histamine stimulates focus, and some aspects of spatial and intellectual functioning, low levels tend to lead to ADHD and hyperactivity, because histamine normally puts the brakes on too much adrenaline, as well as serotonin - histamine is absolutely essential for GABA and acetylcholine release, without histamine - GABA and acetylcholine would sink to the floor.
This is the reason why histamine h3 antagonists are being investigated for low histamine conditions; as they would raise histamine through negative feedback ....and in turn release more GABA and acetylcholine - leading to treatment of mental diseases such as alszheimer's , dementia, schizophrenia, refractory OCD and anxiety disorders.
Posted 04 October 2014 - 09:58 PM
Histone's are totally different than histamine's. From what I've read, histamine is essential to the parasympathetic nervous system, and helps keep you in a relaxed state ; even though it can be stimulating - it's 360 degrees different than the stimulating action of adrenaline.
Histamine stimulates focus, and some aspects of spatial and intellectual functioning, low levels tend to lead to ADHD and hyperactivity, because histamine normally puts the brakes on too much adrenaline, as well as serotonin - histamine is absolutely essential for GABA and acetylcholine release, without histamine - GABA and acetylcholine would sink to the floor.
This is the reason why histamine h3 antagonists are being investigated for low histamine conditions; as they would raise histamine through negative feedback ....and in turn release more GABA and acetylcholine - leading to treatment of mental diseases such as alszheimer's , dementia, schizophrenia, refractory OCD and anxiety disorders.
Posted 06 October 2014 - 03:07 PM
Histone's are totally different than histamine's. From what I've read, histamine is essential to the parasympathetic nervous system, and helps keep you in a relaxed state ; even though it can be stimulating - it's 360 degrees different than the stimulating action of adrenaline.
Histamine stimulates focus, and some aspects of spatial and intellectual functioning, low levels tend to lead to ADHD and hyperactivity, because histamine normally puts the brakes on too much adrenaline, as well as serotonin - histamine is absolutely essential for GABA and acetylcholine release, without histamine - GABA and acetylcholine would sink to the floor.
This is the reason why histamine h3 antagonists are being investigated for low histamine conditions; as they would raise histamine through negative feedback ....and in turn release more GABA and acetylcholine - leading to treatment of mental diseases such as alszheimer's , dementia, schizophrenia, refractory OCD and anxiety disorders.
Ah! Thx Area_1255
Some get them confused from time to time, especially considering there is a lot of overlapping of medical terms. But in contrast, the production and breakdown on enzymes between histone's and histamine's are totally different.
HDC; histidine decarboxylase, is the enzyme by which histamine is synthesized from histidine
Antagonists for reducing histamine ; catechins, hesperidin, EGCG from greentea extract
HDC stimulators ; copper antagonists, histamine h3 antagonists and a few other substrates
HMNT/HMT; histamine methyltransferase - breaks down histamine by methylation, or methylation activates this enzyme, can be inhibited with syrian rue extract or harmala alkaloids
DAO; diamine oxidase, this enzyme breaks down histamine after it's been broken down by histamine methyltransferase and allows it to be eliminated from the body - a copper dependent enzyme
DAO inhibitors would be ; caffeine, folate, mega doses of zinc and anything else that opposes copper
Therefore if you are a low histamine individual....a quick fix would be
Conessine extract. syrian rue, caffeine, folate and high protein diet.
Posted 11 October 2014 - 10:29 PM
Another possible histaminergic, besides modafanil / adrafanil...might possibly be ginkgo biloba...though it's not clear.
In order to clarify the mechanism of Ginkgo biloba extract (GBE) on learning and memory, we studied the effect of GBE on spatial memory deficits induced by diphenhydramine, pyrilamine and scopolamine using the eight-arm radial maze performance of rats, in comparison with donepezil. Total error (TE), reference memory error (RME) and working memory error (WME) were used as indices of spatial memory deficits. Both GBE and donepezil caused a potent antagonistic effect on the increase in TE, RME and WME induced by diphenhydramine. GBE and donepezil also antagonized scopolamine-induced spatial memory deficits. Although the antagonistic effect of GBE on pyrilamine-induced spatial memory deficits was weak, a significant difference was observed with TE and WME. However, donepezil caused no antagonistic effect on pyrilamine-induced memory deficits. From these findings, we concluded that the effects of GBE are mainly contributable to cholinergic activity and perhaps partly due to a histaminergic mechanism.
Posted 12 October 2014 - 12:50 AM
Excuse me, what? I find this very hard to believe. A full 50mg dose of naltrexone causes a reaction similar to a withdrawal from a strong opiate. How on earth could anyone describe that as 'too calming'? I understand that mu antagonism could cause some GABA release to regain balance, but the overall net effect is still negative/towards anxiogenesis. So, please elaborate, which antagonists in what dosages?If you don't get the dose right with opioid antagonists...you will find yourself staring at a wall blankly all day. I find them to have very positive effects, but almost too calming at times. :D
Posted 12 October 2014 - 01:22 AM
Excuse me, what? I find this very hard to believe. A full 50mg dose of naltrexone causes a reaction similar to a withdrawal from a strong opiate. How on earth could anyone describe that as 'too calming'? I understand that mu antagonism could cause some GABA release to regain balance, but the overall net effect is still negative/towards anxiogenesis. So, please elaborate, which antagonists in what dosages?If you don't get the dose right with opioid antagonists...you will find yourself staring at a wall blankly all day. I find them to have very positive effects, but almost too calming at times. :D
Well I've used 25 mg and I felt lethargic as fuck and heart rate was altered, without stims, I was blank minded. Though you are right at 50 mg...It would most definitely cause some bad sides...some of which would be chills, hot flashes, anxiety, depression, rage etc...
Keep in mind though that even at this dose I am keeping my hormones optimal by other means..namely estro-cort modulation so perhaps opiate antagonists have less side-effects when androgens are in tact?
Posted 19 October 2014 - 02:14 PM
I would be very interested to see someone using pitolisant from tht (transhuman technologies) and see what the effects are on hormones...cortisol and ACTH (adreno cortico tropic hormone) in particular.
Somebody better log this shit!
If not them, I will.
Edited by Area-1255, 19 October 2014 - 02:15 PM.
Posted 21 October 2014 - 08:28 PM
I think more people should report on these things, so we can verify past studies like for instance those elaborating histamine's effects on ACTH, cortisol and beta endorphin..but the opposite effect might be achieved because the endocrine effects of h3 blockade hasn't been studied that well...I'm wondering, and trending towards the assumption that the massive enhancement of GABA by blocking h3 receptors , as well as all other nt's that are released, by other histamine receptors..would be enough to over ride the normal cortisol increase produced by histamine -------- and it seems this makes sense from a personal experience, because when on thioperamide i felt less stressed and way more focused and chippy.
Posted 01 November 2014 - 07:15 PM
so is histamine in allergies, does that mean that allergies or exposing oneself to allergens automatically drop blood pressure and what if it is only a slight allergen, does blood pressure still go down? i know histamine rebalances fluids and electrolytes but to what extent and how much of an allergic reaction is needed before blood pressure falls significantly?
Excellent question, but you kinda answered it yourself already.
If it is a mild allergic reaction, then it would depend on what type* of allergic reaction, and specifically if you are talking pets or seasonal or food. The internal response to a food* you are allergic to will usually yield more internal effects on a set time range, and can be very severe, depending on how allergic you are...Seasonal and pet allergies may evoke a skin mediated reaction quicker, but both are about equivalent in terms of effects on hydration status - but again, you are talking apples to oranges here, there will be variation based on YOU and HOW allergic you are, and your susceptibility to allergic responses is also determined by other factors such as stress (which releases histamine to trigger cortisol response), diet and exercise frequency.
Taking a walk even, will raise histamine decarboxylase - and thus more histamine production...and most cardio/calisthenic style workouts trigger histamine response faster than slow movement workouts...unless you are using a lot of weight and it becomes a core body or resistance style workout. These are healthier variants of histamine response however.
Brain and neuronal histamine do not necessarily follow the same rhythm as peripheral histamine release; meaning - you could have high histamine in the brain and nerves but not in the skin or elsewhere...this is entirely possible. You can also have low histamine in the brain and tons in the periphery, although this one is rare and more obscure by contrast.
Keep in mind that histamine is also not the only vasodilator, it simply acts as one (a major one though) out of many nitric oxide promoting chemicals, and also plays a role in oxytocin release and vasopressin release. Generally speaking, the more histamine that builds up, the less vasopressin but more oxytocin, which explains why many high histamine people "wear their heart on their sleeve" and can be over emotional...
High histamine people, partially due to the low vasopressin levels , also tend to be very lean, defined, cut up etc and veins are prominent. So they literally wear their heart on their sleeve, both in the physical sense and psychological one.
Posted 03 November 2014 - 07:57 PM
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