WolfgangA
Devil’s Advocate
- Apr 9, 2019
- 108
I'm thinking about using other methods to get achieve the necessary GABA level and perhaps mix some benzodiazepines are CNS depressants and thus can increase the action of other CNS depressants and can increase sedation, provoke a black out, impaired motor coordination, suppressed breathing and other adverse effects that can be lethal when combined with GABA. And perhaps lower or better yet block cortisol and norepinephrine to enhance the process? Finally alchol maybe?
" Neurologically, barbiturates essentially put patients to sleep by slowing down the brain's electrical activity, by stimulating the gamma-amino-butyric-acid (GABA) receptors. This activates an inhibitory response, which reduces the firing of neurons. If enough of this occurs, breathing slows down and can eventually cease, leading to death. Each barbiturate varies in how fast acting and how long lasting they are, creating major differences a patient's consciousness or pain during death "
In the ppeh under "How Barbiturates work" its mentioned that they work by enhancing effct of GABA in brain and at higher dose may even replace the GABA. Sleep, sedation is induced by enhanced GABA which slows down brain activity. An OD of barbiturates can depress brain functions so severally that respiration ceases and we ctb.
I know that well this seems totally naive and perhaps even dangerous but hear me out, what I'm thinking is if we can take the full working mechanism of barbiturates and break it down piece by piece and remove all the components that play a lesser role, that should leave us with what I'm thinking.
Then we can perhaps manipulate each step with different meds, like "Block x receptor" "block y receptor", we can take two different meds/herbs/something else which doesn't conflict with each other or even if they do, its negligible to some extent. Also their interaction so we know what we're dealing with, I mean as much data as possible so its can hopefully result in peaceful ctb or atleast with minor pain/discomfort maybe? And yes adding more components(meds) complicates things but I would like to explore the idea and hopefully we'll figure out if its viable.
Before we we get into the depth, a heavy portion of this article goes over my head but from what little I understand, perhaps there could be some potential, need expert insights.
GABA + benzo should potentate the solution resulting in reduced amount of drug requirement, would be nice to know how much or some similar data perhaps?
Anyone know of other possible ways to stimulating "gamma-amino-butyric-acid (GABA) receptors" through different means such as one drug or multi-drug combo maybe?
" Barbiturates act as positive allosteric modulators, and at higher doses, as agonists of GABAA receptors.[19] GABA is the principal inhibitory neurotransmitter in the mammaliancentral nervous system (CNS). Barbiturates bind to the GABAA receptor at multiple homologous transmembrane pockets located at subunit interfaces,[20] which are binding sites distinct from GABA itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. In addition to this GABAergic effect, barbiturates also block AMPA and kainate receptors, subtypes of ionotropic glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. Taken together, the findings that barbiturates potentiate inhibitory GABAA receptors and inhibit excitatory AMPA receptors can explain the superior CNS-depressant effects of these agents to alternative GABA potentiating agents such as benzodiazepines and quinazolinones. At higher concentration, they inhibit the Ca2+-dependent release of neurotransmitters such as glutamate via an effect on P/Q-type voltage-dependent calcium channels.[21] Barbiturates produce their pharmacological effects by increasing the duration of chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the efficacy of GABA), whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABAA receptor (pharmacodynamics: This increases the potency of GABA). The direct gating or opening of the chloride ion channel is the reason for the increased toxicity of barbiturates compared to benzodiazepines in overdose.[22][23] "
Further, barbiturates are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is only one of several representatives. This Cys-loop receptor superfamily of ion channels includes the neuronal nACh receptor channel, the 5-HT3 receptor channel, and the glycine receptorchannel. However, while GABAA receptor currents are increased by barbiturates (and other general anaesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nAChR channels are blocked by clinically relevant anaesthetic concentrations of both thiopental and pentobarbital.[24] Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates.[25] This is the mechanism responsible for the (mild to moderate) anesthetic effect of barbiturates in high doses when used in anesthetic concentration.
I understand the "block MPA and kainate receptors", afterwards I'm lost.
Manipulating which receptors and/or anything else would replicate the effect of barbiturates?
Pregablin (Lyrica)
Said to be quite potent but LD50 for humans unknown.
Gabapentin
Mouse Oral LD50 > 5000 mg/kg
According to the case reports and also adding in other instances of anecdoal data from random sites, it seems LD50 requires really high amount.
I like the idea of Cortisol receptor antagonists which blocking Cortisol (also called "stree hormone") action throughtout the body.
Reduce cortisol level
Cortisol Receptor Antagonists
Cortisol receptor antagonists are medications that block the actions of cortisol throughout the body. They do not directly lower cortisol levels. Mifepristone (Korlym, Mifeprex), a drug initially developed as an abortion pill, is the main cortisol receptor antagonist used to treat high cortisol levels."
Reduce Norepinephrine level
" Serotonin Reuptake Inhibitors
Selective serotonin reuptake inhibitors belong to a class of drugs that have anti-depressant and anxiolytic, or anti-anxiety, effects. They block the absorption of brain serotonin back into the neurons.
GABA supplements
Good read.
A number of articles mentioned here and from other research suggests "pharmaGABA" is the goto brand when it comes supplement.
Also need to know how the GABA supplements work, like benzo's by amplifying the effect of the human body's own GABA and that has a natural limit or perhaps the other way around like pentobarbs where they have no limit (virtually).
Is there anyway to know brains tolerance to GABA (if applicable)? Blood test?
Finally I'm hoping to find an alternative to mimic pentobarbital.
Navigating the new era of assisted suicide and execution drugs
Lethal medication provisions are in a precarious state. Over the past decade, pharmaceutical companies have attempted to stamp out the use of their drugs i
academic.oup.com
In the ppeh under "How Barbiturates work" its mentioned that they work by enhancing effct of GABA in brain and at higher dose may even replace the GABA. Sleep, sedation is induced by enhanced GABA which slows down brain activity. An OD of barbiturates can depress brain functions so severally that respiration ceases and we ctb.
I know that well this seems totally naive and perhaps even dangerous but hear me out, what I'm thinking is if we can take the full working mechanism of barbiturates and break it down piece by piece and remove all the components that play a lesser role, that should leave us with what I'm thinking.
Then we can perhaps manipulate each step with different meds, like "Block x receptor" "block y receptor", we can take two different meds/herbs/something else which doesn't conflict with each other or even if they do, its negligible to some extent. Also their interaction so we know what we're dealing with, I mean as much data as possible so its can hopefully result in peaceful ctb or atleast with minor pain/discomfort maybe? And yes adding more components(meds) complicates things but I would like to explore the idea and hopefully we'll figure out if its viable.
Before we we get into the depth, a heavy portion of this article goes over my head but from what little I understand, perhaps there could be some potential, need expert insights.
GABA + benzo should potentate the solution resulting in reduced amount of drug requirement, would be nice to know how much or some similar data perhaps?
Anyone know of other possible ways to stimulating "gamma-amino-butyric-acid (GABA) receptors" through different means such as one drug or multi-drug combo maybe?
Barbiturate - Wikipedia
en.wikipedia.org
Further, barbiturates are relatively non-selective compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABAA receptor channel is only one of several representatives. This Cys-loop receptor superfamily of ion channels includes the neuronal nACh receptor channel, the 5-HT3 receptor channel, and the glycine receptorchannel. However, while GABAA receptor currents are increased by barbiturates (and other general anaesthetics), ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nAChR channels are blocked by clinically relevant anaesthetic concentrations of both thiopental and pentobarbital.[24] Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates.[25] This is the mechanism responsible for the (mild to moderate) anesthetic effect of barbiturates in high doses when used in anesthetic concentration.
I understand the "block MPA and kainate receptors", afterwards I'm lost.
Manipulating which receptors and/or anything else would replicate the effect of barbiturates?
Pregablin (Lyrica)
Said to be quite potent but LD50 for humans unknown.
Gabapentin
Mouse Oral LD50 > 5000 mg/kg
TOXNET HAS MOVED
toxnet.nlm.nih.gov
I like the idea of Cortisol receptor antagonists which blocking Cortisol (also called "stree hormone") action throughtout the body.
Reduce cortisol level
Cortisol Receptor Antagonists
Cortisol receptor antagonists are medications that block the actions of cortisol throughout the body. They do not directly lower cortisol levels. Mifepristone (Korlym, Mifeprex), a drug initially developed as an abortion pill, is the main cortisol receptor antagonist used to treat high cortisol levels."
Reduce Norepinephrine level
Drugs and Medications | Livestrong.com
Our drugs and medications page offers comprehensive information on many prescription and over-the-counter drugs, including uses, side effects and interactions. "At our drugs and med...
www.livestrong.com
Selective serotonin reuptake inhibitors belong to a class of drugs that have anti-depressant and anxiolytic, or anti-anxiety, effects. They block the absorption of brain serotonin back into the neurons.
GABA supplements
The Best GABA Supplement You Will Ever Need | gammaaminobutyricacid.org
If you're looking to buy GABA supplements online, look no further. The top gamma-aminobutyric acid pill review is right here.
www.gammaaminobutyricacid.org
A number of articles mentioned here and from other research suggests "pharmaGABA" is the goto brand when it comes supplement.
Also need to know how the GABA supplements work, like benzo's by amplifying the effect of the human body's own GABA and that has a natural limit or perhaps the other way around like pentobarbs where they have no limit (virtually).
Is there anyway to know brains tolerance to GABA (if applicable)? Blood test?
Finally I'm hoping to find an alternative to mimic pentobarbital.
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