AlloP - Liquid Allopregnanolone For Lab/R&D

[Blazko]

Wow very excited about this one. Hats off Haidut for persevering and getting this done. Any specific studies for Allopregnanolone and Parkinson's disease?

Not directly related to Parkinson's disease, but I have read a full study on the effect of allopregnanolone (APα) on a model of Alzheimer's disease (AD) in mice:

Allopregnanolone enhances the neurogenesis of midbrain dopaminergic neurons in APPswe/PSEN1 mice
and in the full article there was:

In addition to cognitive impairment, 35–40% of AD patients can slowly develop extra-pyramidal motor signs or Parkinson’s disease (PD)-like syndromes which increase in prevalence with the developing of AD (Morris et al., 1989; Lopez et al., 1997).

For example, the mice expressing familial AD-linked mutant human amyloid precursor proteins (APPs) exhibit degeneration in the midbrain dopaminergic neurons and PD like motor deficits (Masliah et al., 2001).

As a neurogenic agent with a low molecular weight and easily penetrating blood–brain barrier, APα may potentially treat or prevent parkinsonian symptoms in AD patients.

Compared with the serum and cerebral spinal fluid of age-matched healthy subjects, APα level is much lower in the PD patients (di Michele et al., 2003; Marx et al., 2006; Luchetti et al., 2010; Naylor et al., 2010), which is consistent with evidence that the expression of genes involved in encoding enzymes for APα synthesis is decreased in the post-mortem brain samples of PD subjects (Marx et al., 2006; Naylor et al., 2010).

 

[Soren]

Not directly related to Parkinson's disease, but I have read a full study on the effect of allopregnanolone (APα) on a model of Alzheimer's disease (AD) in mice:

Allopregnanolone enhances the neurogenesis of midbrain dopaminergic neurons in APPswe/PSEN1 mice
and in the full article there was:

Thanks for sharing this Blazko. I would argue that this has direct implications for PD as the mainstream theory is that PD is caused by loss of dopamegenic neurons. Although I think it is more likely caused by excess Serotonin rather than insufficient dopamine

 

[Blazko]

Thanks for sharing this Blazko. I would argue that this has direct implications for PD as the mainstream theory is that PD is caused by loss of dopamegenic neurons. Although I think it is more likely caused by excess Serotonin rather than insufficient dopamine

I agree that this has direct implications for PD.

Allopregnanolone enhances the neurogenesis of midbrain dopaminergic neurons in APPswe/PSEN1 mice

When APα was injected to 2xTgAD mice, we found that the number of Nissl-stained neurons and TH-positive neurons was increased by 28.6% (Fig. 2E) and 16.4% (Fig. 2F) in the SNpc, respectively.

APα = Allopregnanolone, 2xTgAD = Alzheimer's model

APα failed to reverse the decrease of TH-positive neural fibers in the striatum of 2xTgAD mice.

In the 2xTgAD mice treated with APα, the number of BrdU-labeled cells and BrdU/TH double-labeled neurons was increased by 19.1% (p = 0.001) and 64.5% (p = 0.048), respectively (Fig. 4D, E). These data suggested that APα treatment could exert a remarkable effect in promoting the generation of new-born TH-positive neurons.

In the SVZ, APα treatment could restore the decreasing number of total DCX-positive neurons and DCX/BrdU double-positive neurons in the 2xTgAD mice (p < 0.001, Fig. 5D, E). In the SGZ, there was no significant difference in the total DCX-positive neurons (p = 0.12), although the number of DCX/BrdU doublepositive neurons in the DMSO-2xTgAD mice was much lower than that in the APα-Non-Tg mice (p = 0.002) (Fig. 6D, E).

APα, as a potent promoter of neurogenesis, can induce a significant increase in rat hippocampal neural progenitor cells and human neural stem cells from the cerebral cortex (Wang et al., 2005).

APα concentration required to elicit the neurogenesis is within the 109–107 M range (Wang et al., 2005). In this study, 20 mg/kg dose of APα gave rise to 0.59 109 M (189.07 pg/ml) or 0.41 109 mol/kg (131.57 pg/g) of APα level in the serum or cerebral cortex of 4-month-old 2xTgAD mice when examined at 2 h after APα injection, which might restore an integrity of positive feedback between APα and neuronal progenitor cells in the brain and eventually lead to the recovery of TH-positive neurons in the SNpc of 2xTgAD mice.

Parkinson's disease is characterized by degeneration and death of dopaminergic neurons in the striatum and substantia nigra. The study shows that allopregnanolone increased the number of dopaminergic neurons in substantia nigra, but failed to do so in striatum. Still, it is remarkable.

There's also another theory about PD:
Waking up dormant dopaminergic neurons to reverse Parkinson's disease

 

[Vincent123]

@haidut Literature states adult males produce between 5–15 mg of progesterone per day, perhaps 8 mg of progesterone twice daily would be optimal an optimal replacement dose in theory. That said, I cannot find any literature regarding how much Allopregnanolone is synthesized endogenously. I would really like to know how much alloP would be sufficient for lab use with an adult male organism mimicking a human who does not have 5ar conversion capabilities, therefore alloP conversion.

 

[chompie]

Just a quick announcement that we have replaced the 5α-DHP in our store with allopregnanolone. The main reason for switching over to allopregnanolone is that we always wanted to provide that steroid right from the start, however we could not find a lab willing to synthesize it. Thus, 5α-DHP (being a direct precursor to allopregnanolone) was the most feasible option until we could find a source of allopregnanolone. Well, now we have it and as such we will no longer be selling the 5α-DHP.

A different reason was given here: 5α-DHP - Liquid 5α-Dihydroprogesterone For Lab/R&D

Would you mind explaining what changed?

 

[Epistrophy]

I have been having good experience with 5 drops. I was wondering if taking everyday would 5 drops eventually have no effect and an increase of dose needed?

 

[shine]

I have been having good experience with 5 drops. I was wondering if taking everyday would 5 drops eventually have no effect and an increase of dose needed?

That's likely.

Tolerance to allopregnanolone with focus on the GABA-A receptor

Many studies have suggested a relationship between stress, sex steroids, and negative mental and mood changes in humans. The progesterone metabolite allopregnanolone is a potent endogenous ligand of the γ-amino butyric acid –A (GABA-A) ...

www.ncbi.nlm.nih.gov

 

[Epistrophy]

I have been taking Allop (5 drops, oral) and today I used 4 drops 11k-DHT which had not been on my regime in a bit. I honestly can say that today was the only time taking 11k-DHT feeling the effects of this compound, which was harder abdominal muscles. @haidut You think there is some synergy or I wonder if allopregnanolone is freeing up enzymes to use 11k-DHT?

 

[CoconutEffect]

How are folks doing with this?

 

[CoconutEffect]

Should dose be 30mg / day for 14 days?

Sage Therapeutics Announces Continued Positive Zuranolone Data for Both 30 mg and 50 mg Doses in Open-Label SHORELINE Study in Patients with MDD

Sage Therapeutics, Inc. (Nasdaq: SAGE) today reported complete 12-month data from the 30 mg cohort and interim data from the 50 mg cohort of the ongoi

www.businesswire.com

 

[CoconutEffect]

Bump

 

[K-Dog]

Anyone from Germany who ordered this? Did you get it through the customs without problems?

 

[themartian1000]

I found that this may have helped or may have been placebo. However, 5 alpha DHP was so much better. Too bad we couldn't have both.

 

[GorillaHead]

I am super excited for this. Surprised this isn’t a 40 page thread.

If this doesn’t suppress endogenous production then this is about to be one of the best things to have on hand.

If I am correct the right dosage should make you perfectly confident. This is the alpha male neurohormone IMO.

 

[Soren]

Anyone have anything to report in terms of topical vs oral supplementation?

 

[golder]

I am super excited for this. Surprised this isn’t a 40 page thread.

If this doesn’t suppress endogenous production then this is about to be one of the best things to have on hand.

If I am correct the right dosage should make you perfectly confident. This is the alpha male neurohormone IMO.

I’ve not tried it yet but I was also expecting some incredible reports, but there hasn’t been as much as I was expecting. Perhaps because it’s quite new not that many have trialled it yet.

 

[korpesh]

I found that this may have helped or may have been placebo. However, 5 alpha DHP was so much better. Too bad we couldn't have both.

I second this. 5a DHP was may more consistent at giving me calm boost in mood and energy, as well as probably lowering prolactin. Allo seems very inconsistent to me... sometimes good, sometimes bad.

 

[MOUNTAINBEAR]

40 year old male here. Took AlloP several times now. It gives me a positive outlook on life, feeling optimistic, getting things done, looking for solutions (and finding alternative ways to solve them), open to others, easy to talk to others, don't feel annoyed by people and kids. Today I had it with one drop of 11ketoDHT (on my navel) my sex drive was very high, I could feel my **** tingling. Just ordered 3 more. Don't even feel like taking cannabis or cigarettes. Will report back after a more prolonged use. But I can fall asleep even if I drink a lot of espressos without the need for melatonin. I take it in the morning, about 7-10 drops.

 

[Hermes]

40 year old male here. Took AlloP several times now. It gives me a positive outlook on life, feeling optimistic, getting things done, looking for solutions (and finding alternative ways to solve them), open to others, easy to talk to others, don't feel annoyed by people and kids. Today I had it with one drop of 11ketoDHT (on my navel) my sex drive was very high, I could feel my **** tingling. Just ordered 3 more. Don't even feel like taking cannabis or cigarettes. Will report back after a more prolonged use. But I can fall asleep even if I drink a lot of espressos without the need for melatonin. I take it in the morning, about 7-10 drops.

Thanks for sharing your experience. Have you applied the AlloP topically like 11ketoDHT? So far I've used it topically and tried today orally, five drops. I think it's working even better orally.

 

[MOUNTAINBEAR]

alloP orally, 11ketoDHT topically

I guess it could just accentuate an underlying character trait, but I'm just more organised and in a gogetting mode