Lisuride - Liquid Lisuride For Lab/R&D

[Mauritio]

applied 1 drop on the forearm.
felt sleepy and I actually have to take a nap in 30min/body temp and apetite increased/very calm and relaxed/got constipation
exciting to see how it synergize with Diamant.

Did you try to combine Diamant and Lisuride , if so what effects did you feel ?

 

[japanesedude]

I haven't tried yet cuz Im not sure its safe or not.

 

[Mauritio]

Oh okay, i think not combining it with methylene blue makes sense since both chemicals have possible serotonergic sides but afaik dimant doesnt ..

 

[Mauritio]

I haven't tried yet cuz Im not sure its safe or not.

Update:
I have tried both together on Sunday and I didn't feel well. Cant quite put my finger on it but could be some serotonergic activity going on there. Was having worse mood and energy , nothing concerning just didn't match really well together.

 

[japanesedude]

too much stimulation maybe?
a japanese lab rat tried a drop on his testes once and It was one hell of experience.
It is better to apply it on the wrist or forearm. 1 or 2 drops are good enough for him.

 

[Mauritio]

I have repeatedly tried Lirsuride on testes with good results , so that doesn't bother me. But I guess with the potentiating effect of Diamant you fastly reach the terrain where Lisuride becomes serotonergic...Just my guess.

 

[japanesedude]

I've never stacked it with Lisuride.
but yeah,using substances on testes always have daramatic effects.

 

[Douglas Ek]

@haidut
You say Lisuride is a generally considered a 5-ht2A antagonist but wikipedia list it as an partal agonist
5-HT2A receptor - Wikipedia
They're just wrong about it?
They also list that 5-ht2A is responsible for LSD and DMTs hallucinogenic effects thus this would had mean that lisuride should had some hallucinogenic effects but it doesn't right?

 

[haidut]

@haidut
You say Lisuride is a generally considered a 5-ht2A antagonist but wikipedia list it as an partal agonist
5-HT2A receptor - Wikipedia
They're just wrong about it?
They also list that 5-ht2A is responsible for LSD and DMTs hallucinogenic effects thus this would had mean that lisuride should had some hallucinogenic effects but it doesn't right?

It is precisely the fact that lisuride does NOT have hallucinogenic effects and reliably stops LSD "trips" that strongly suggests it is an antagonist on 5-HT2A. But the exact agonism/antagonism of all ergot derivatives is not really known and not much research is done with them these days as medicine does not like these older, generic chemials. No profit in them whatsoever.

 

[thomas00]

Has his product been increased to 50mcg per drop, Haidut?

 

[haidut]

Has his product been increased to 50mcg per drop, Haidut?

Nope. Where did you see that stated?

 

[Luckytype]

Nope. Where did you see that stated?

The label on the bottle says it.

 

[haidut]

The label on the bottle says it.

We had a few batches that had 50mcg per drop because the lisuride powder we had at the time was older and our lab said about 62% of lisuride was still present intact in the powder. But we are now back to using a fresh powder batch and the lab's analysis is 99%+ (99.2% to be precise) concentration so we are back to 25mcg per drop.

 

[Luckytype]

We had a few batches that had 50mcg per drop because the lisuride powder we had at the time was older and our lab said about 62% of lisuride was still present intact in the powder. But we are now back to using a fresh powder batch and the lab's analysis is 99%+ (99.2% to be precise) concentration so we are back to 25mcg per drop.

Do you have any concerns over any of this regarding the potency over time considering what the lab found versus what im guessing your expectations were?

 

[haidut]

Do you have any concerns over any of this regarding the potency over time considering what the lab found versus what im guessing your expectations were?

We buy lisuride once every 2 years. So, the latest batches had powder that was bought almost 2 years ago and was manufactured a year before we bought it. So, 38% loss over 3 years is not bad. Also, considering FDA mandates liquid products (including lab chemicals) to be advertised with no more than 12 months of shelf life this should not be an issue for most people buying them. Using simple averaging over the 3 years this comes down to about 12% loss per year, which I think is acceptable.

 

[Mauritio]

We had a few batches that had 50mcg per drop because the lisuride powder we had at the time was older and our lab said about 62% of lisuride was still present intact in the powder. But we are now back to using a fresh powder batch and the lab's analysis is 99%+ (99.2% to be precise) concentration so we are back to 25mcg per drop.

Maybe its just me , but why would the older powder have more potency per drop ?

 

[Logan-]

Actually, the exact profile of lisuride on the 5-HT receptors is not well-known other than its clear antagonism on 5-HT2B, which makes it an excellent anti-fibrotic agent.

Haidut, if the 5-ht2b antagonism is the mechanism behind its anti-fibrotic quality, does that mean all the other 5-ht2b antagonists have the same anti-fibrotic quality?

I think the etiology of fibrosis is largely the same, regardless of the organ where it manifests itself. Antagonists of 5-HT2B have been found to be therapeutic for fibrosis regardless of the location.

I think lisuride, cabergoline and bromocriptine would be pretty close to LSD effects but without the hallucinogenic ones. These are all mixed dopamine/serotonin agonists with predominant dopaminergic effects like LSD. Metergoline is a proper anti-serotonin and is probably not a good mimic of LSD even though it is technically also an LSD derivative.

This chemical metergoline is a very interesting substance and is a continuation of my search for chemicals that combine several beneficial characteristics into a single molecule/entity. Metergoline belongs to the same class of drugs as bromocriptine, lisuride, cabergoline, terguride, etc. However, unlike them it is a potent antagonist on the serotonin receptors 5-HT1, 5-HT2, 5-HT6, and 5-HT7. Most ergot drugs are agonists on those receptors with the possible (and partial) exception of lisuride. More importantly, just like lisuride metergoline is a potent antagonist on the dreaded 5-HT2B receptor. This endows it with anti-fibrotic properties similar to lisuride, terguride, ritanserin and cyproheptadine.

Fig. 6
Open in a separate window
Potential pathways of 5-HT2B. 5-HT2B activation may lead to proliferation through pathways that depend on ERK1/2, Src, and PKC. Additionally, 5-HT2B may crosstalk directly with TGF-β1 signaling via interaction with Src. A 5-HT2B antagonist may function as an inverse agonist to inhibit these pathways and prevent the fibrotic response of VICs that leads to HVD. Reprinted with permissions from (Roth 2007).

As noted above, many 5-HT2B receptor antagonists are currently FDA-approved and used clinically to treat other diseases, with acceptable tolerance (including but not limited to: Amesergide, Amisulpride, Bromocryptine, Lisuride, Chlorpromazine, Clozapine, Cyproheptidine, Metergoline, Mianserin, Olanzapine, Aripiprazole, Risperidone, 9-OH-risperidone, Terguride, Yohimbine, Ziprasidone, Roxindole). Furthermore, it is interesting to note that lisuride has been shown to be an antagonist at 5-HT2B receptors (Newman-Tancredi, Cussac et al. 2002; Elangbam 2010) and was prescribed for more than 30 years without a single known report of HVD (Hofmann, Penner et al. 2006).

Source: Hutcheson, Joshua D et al. “Serotonin receptors and heart valve disease--it was meant 2B” Pharmacology & therapeutics vol. 132,2 (2011): 146-57.

Why does Methysergide has the known fibrotic property?

Methysergide interacts with serotonin (5-HT) receptors. Its therapeutic effect in migraine prophylaxis has been associated with its antagonism at the 5-HT2B receptor.[7]

It is also used in carcinoid syndrome to treat severe diarrhea.[1] It may also be used in the treatment of serotonin syndrome.[4]

It has a known side effect, retroperitoneal fibrosis/retropulmonary fibrosis,[5] which is severe, although uncommon. This side effect has been estimated to occur in 1/5000 patients.[6] In addition, there is an increased risk of left-sided cardiac valve dysfunction.[2]

Methysergide was synthesized from lysergic acid by adding a methyl group and a butanolamid group. This resulted in a compound with selectivity and high potency as a serotonin (5-HT) inhibitor. Based on the possible involvement of serotonin in migraine attacks, it was introduced in 1959 by Sicuteri as a preventive drug for migraine. The clinical effect was often excellent, but 5 years later it was found to cause retroperitoneal fibrosis after chronic intake.

Methysergide has been an effective treatment for migraine and cluster headache for over 50 years but has systematically been suppressed from the migraine and cluster headache marketplace for over 15 years due to unqualified risk benefit/ratio safety concerns.[16]

Many cite the potential side effects of retroperitoneal/retropulmonary fibrosis as the prime reason methysergide is no longer frequently prescribed, but retroperitoneal fibrosis, and retropulmonary fibrosis, were documented as side effects as early as 1966,[17] and 1967,[18] respectively.

Methysergide - Wikipedia

 

[haidut]

Haidut, if the 5-ht2b antagonism is the mechanism behind its anti-fibrotic quality, does that mean all the other 5-ht2b antagonists have the same anti-fibrotic quality?

Fig. 6
Open in a separate window
Potential pathways of 5-HT2B. 5-HT2B activation may lead to proliferation through pathways that depend on ERK1/2, Src, and PKC. Additionally, 5-HT2B may crosstalk directly with TGF-β1 signaling via interaction with Src. A 5-HT2B antagonist may function as an inverse agonist to inhibit these pathways and prevent the fibrotic response of VICs that leads to HVD. Reprinted with permissions from (Roth 2007).

As noted above, many 5-HT2B receptor antagonists are currently FDA-approved and used clinically to treat other diseases, with acceptable tolerance (including but not limited to: Amesergide, Amisulpride, Bromocryptine, Lisuride, Chlorpromazine, Clozapine, Cyproheptidine, Metergoline, Mianserin, Olanzapine, Aripiprazole, Risperidone, 9-OH-risperidone, Terguride, Yohimbine, Ziprasidone, Roxindole). Furthermore, it is interesting to note that lisuride has been shown to be an antagonist at 5-HT2B receptors (Newman-Tancredi, Cussac et al. 2002; Elangbam 2010) and was prescribed for more than 30 years without a single known report of HVD (Hofmann, Penner et al. 2006).

Source: Hutcheson, Joshua D et al. “Serotonin receptors and heart valve disease--it was meant 2B” Pharmacology & therapeutics vol. 132,2 (2011): 146-57.

Why does Methysergide has the known fibrotic property?











Methysergide - Wikipedia

I would say, generally yes, all 5-HT2B antatgonists should have similar effects for fibrosis. That is why Pfizer bought the drug terguride (dihydro-lisuride) and runs clinical trials with it for many conditions.
Terguride - Wikipedia

 

[Logan-]

I would say, generally yes, all 5-HT2B antatgonists should have similar effects for fibrosis. That is why Pfizer bought the drug terguride (dihydro-lisuride) and runs clinical trials with it for many conditions.
Terguride - Wikipedia

My question was, why does Methysergide cause fibrosis if it is also a 5-HT2B antagonist?

 

[haidut]

My question was, why does Methysergide cause fibrosis if it is also a 5-HT2B antagonist?

The ergot derivatives are not very well understood. It is quite possible that methyseride is a partial agonist there. For lisuride and terguride it has been confirmed that they block 5-HT2B and this is probably why Pfizer went with terguride and not methysergide.