Research /pathological mechanisms

[[De...]]

Diazepam-Induced Down-Regulation of the GABAA receptor α1 Subunit, as mediated by the activation of L-Type Voltage-Gated calcium Channel/Ca2+/Protein kinase a signaling cascade

 

https://pubmed.ncbi.nlm.nih.gov/37356564/

 

 

 

Up-regulation of L-type high voltage-gated calcium channel subunits by sustained exposure to 1,4- and 1,5-benzodiazepines in cerebrocortical neurons

 

 

 

https://pubmed.ncbi.nlm.nih.gov/17949410/

 

Diazepam-induced transcriptional regulation of GABAA receptor alpha 1 subunit via L-type voltage-gated calcium channel activation 1 subunit gene in rat cerebrocortical neurons

 

https://ri.conicet.gov.ar/handle/11336/196720

 

Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice. Neurochem Int.

 

 

 

https://pubmed.ncbi.nlm.nih.gov/27395789/#:~:text=Parkinsonism in mice-,Nimodipine%2C an L-type calcium channel blocker attenuates mitochondrial dysfunctions,Neurochem Int.

 

 

 

 

 

Activation of GABA(A) receptors inhibits T cell proliferation

 

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136847/

 

Diazepam inhibits calcium, calmodulin-dependent protein kinase in primary astrocyte cultures

 

https://pubmed.ncbi.nlm.nih.gov/2540886/

 

 

 

Diazepam Accelerates GABAAR Synaptic Exchange and Alters Intracellular Trafficking

 

 

 

https://www.frontiersin.org/articles/10.3389/fncel.2019.00163/full

 

 

 

L-type channels are extensively distributed on central neurons [38, 39], and play significant roles in dendritic and somatic Ca2+ accumulation [40-42], gene expression [43], and excitability [44]. While regulated Ca2+ accumulation underlies much physiological signaling, un-regulated neuronal Ca2+ overload has long been established as a mechanism of neuronal injury. 

 

 

 

Nimodipine Reappraised: An Old Drug with a Future

 

 

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327937/

 

 

 

ytes and ...

 

de S Leisz · 2019 · Citado por 29 — The calcium antagonist nimodipine binds to the α1-subunit of calcium channels and regulates the calcium influx. Nimodipine treatment is used ...

 

Nimodipine-Dependent Protection of Schwann Cells, Astrocytes and Neuronal Cells from Osmotic, Oxidative and Heat Stress Is Associated with the Activation of AKT and CREB

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770698/

 

 

https://www.mdpi.com/1422-0067/23/6/3331

 

 

 

Impact of the Voltage-Gated Calcium Channel Antagonist Nimodipine on the Development of Oligodendrocyte Precursor Cells

 

https://www.mdpi.com/1422-0067/24/4/3716

 

Nimodipine Exerts Beneficial Effects on the Rat Oligodendrocyte Cell Line OLN-93 (MS)

 

https://www.mdpi.com/2076-3425/12/4/476

 

SAHA (Vorinostat) Corrects Inhibitory Synaptic Deficits Caused by Missense Epilepsy Mutations to the GABAA Receptor γ2 Subunit

 

https://www.frontiersin.org/articles/10.3389/fnmol.2018.00089/full

 

 

Proteostasis regulators restore function of epilepsy-associated GABAA receptors

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855620/#R17

 

Hyposensitivity to Gamma-Aminobutyric Acid in the Ventral Tegmental Area During Alcohol Withdrawal: Reversal by Histone Deacetylase Inhibitors

 

https://research-repository.griffith.edu.au/handle/10072/55370

Edited February 26 by [De...]

[[Na...]]

Lot of great research there to digest. Will take a while.

Do you see anything that suggests a specific treatment?

HDAC inhibitors have been on my radar but I have never tried one.

Edited February 27 by [Na...]

[[De...]]

@[Na...]a "editing" i think that this specific pathological mechanism of regulation at α1-subunit of calcium channels  would be wise to target with nimodipine, It seems to also affect peripheral nerves, immune system and genetic transcription

 

I saw very few reports on BB about this particular substance

 

Regarding HDAC inhibitors

Im not in the US but im asking my cousing to bring me some bempedoic acid which is an HDAC 6 inhibitor, as It seems to have an effect on microtúbules and the pathological adaptations of neuropathy and nerve damages, bempedoic acid is on the market for those who cant tolerate statins but could bê repourposed as an HDAC 6 inhibitor 

 

Im interested in buying vorinostrat, i have a good reliable contact that can synthetize It in a lab, but we need buyers to get a good price for gram, If anyone interested please send a message, plan is to set a group buy, at longecity fórum there is a thread about It, and between 10-40 mg, 3 times a week which are far less than doses for cancer(800mg daily )It seems to already have the desirable effect, seems to modulate some of the acquired pain pathology and gain of function of íon channels trough gene expression, aside from mild immunesupressive/antiinflamatory which might bê mild at this doses and aside from restoring the hyposensitivity of gaba receptors to gaba 

 

 

I have nimodipine hold on customs, i will see a neurologist in the following days and ask for an script 

Edited February 27 by [De...]

[[De...]]

Another update

 

Calcium entry through L-type calcium channels causes mitochondrial disruption and chromaffin cell death

 

https://pubmed.ncbi.nlm.nih.gov/11500491?g=a9dd378cb897e43411052ee070f481ac 

Edited February 27 by [De...]

[[4M...]]

Your best bet would be to synthesize Garcinol.  Not only is it a HDAC11 inhibitor but  Its also very epigenetic.

It increases GAD65 expression which is shown to be downregulated by Benzos long term.

It increases GABAa expression. 

Its anti-cancer. It induces apoptosis in cancer cells but blocks apoptosis in healthy brain cells.

It's also a natural compound found in garcinia indica.

I would be down to go in on getting some Garcinol Fo sho.

 

 

Edited March 6 by [4M...]

[[De...]]

@[4M...] thanks for the contribution, i can check with the lab that i have contact, they are reliable, do you know the doses that would fit ? I can then check what would be a desirable ammount to bê synthetized to get the best possible price, if people here are interested in vorinostrat and garcinol, send me a  private message and let me know 

 

I will check Its toxicology, If something concerns me i let you know, Garcinia cambogia might bê liver tóxic for some 

Edited March 7 by [De...]