Mauritio
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- Feb 26, 2018
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In this study they showed that administering pregnenolone to rats with parkinsons ameliorated the dyskinesia, caused by L-DOPA.
The Human equivalent dosages were 75mg, 225mg and 450mg per day. There was a dose-response effect, meaning higher dose = more effective.
Now they often get the MoA wrong in these studies. Here too: they suppose that pregnenolone helped because of an anti-5AR effect and also because it has an antidopaminergic effect. If anything pregnenolone is the opposite pro-5AR and pro-dopamine. It is only anti-dopaminergic in the sense that it incraeses GABAergic tone, but that is certainly healthy. They also showed that pregnenolone didnt remove the positive effects of L-DOPA, proving that there is likely no anti-dopamine effect or at least that the MoA was somethig else.
Plus: they show that inhibiting 5AR increases pregnenolone in the brain, which is not suprsing, if you inhibit a clompete pathway that preg can convert into (5 alpha-reduced neurosteroids like 5aDHP), that more of the raw material remains as it is.
Based on this faulty hypothesis they use dutasteride as a positive control... Now it was effective, but I suppose another hypothesis for its effectivenes than 5AR-inhibition, namely that dutasteride is a potent endotoxin antagonist (Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain Study - PubMed) !. And the relation between endotoxin --> serotonin --> parkinsons is well known (Parkinson Disease May Start In The Gut).
To suppose that a drug has only this one mechanism and doesn't affect the body in any other way is kind of reductionistic and ignorant.
They also looked at the effects of the different doasges of preg on hormones, which was interesting. So if that interests you check that out.
- Pregnenolone for the treatment of L-DOPA-induced dyskinesia in Parkinson's disease
The Human equivalent dosages were 75mg, 225mg and 450mg per day. There was a dose-response effect, meaning higher dose = more effective.
Now they often get the MoA wrong in these studies. Here too: they suppose that pregnenolone helped because of an anti-5AR effect and also because it has an antidopaminergic effect. If anything pregnenolone is the opposite pro-5AR and pro-dopamine. It is only anti-dopaminergic in the sense that it incraeses GABAergic tone, but that is certainly healthy. They also showed that pregnenolone didnt remove the positive effects of L-DOPA, proving that there is likely no anti-dopamine effect or at least that the MoA was somethig else.
Plus: they show that inhibiting 5AR increases pregnenolone in the brain, which is not suprsing, if you inhibit a clompete pathway that preg can convert into (5 alpha-reduced neurosteroids like 5aDHP), that more of the raw material remains as it is.
Based on this faulty hypothesis they use dutasteride as a positive control... Now it was effective, but I suppose another hypothesis for its effectivenes than 5AR-inhibition, namely that dutasteride is a potent endotoxin antagonist (Inhibitory Effects of Dutasteride on TLR4: An In vitro Pain Study - PubMed) !. And the relation between endotoxin --> serotonin --> parkinsons is well known (Parkinson Disease May Start In The Gut).
To suppose that a drug has only this one mechanism and doesn't affect the body in any other way is kind of reductionistic and ignorant.
They also looked at the effects of the different doasges of preg on hormones, which was interesting. So if that interests you check that out.
- Pregnenolone for the treatment of L-DOPA-induced dyskinesia in Parkinson's disease
