Avermectin B1a: An irreversible activator of the γ-aminobutyric acid-benzodiazepine-chloride-ionophore receptor complex

[[De...]]

 

 

632-638

Avermectin B1a: An irreversible activator of the γ-aminobutyric acid-benzodiazepine-chloride-ionophore receptor complex

 

Avermectin B1a markedly increased the binding of [3H]diazepam to benzodiazepine receptors. This effect was qualitatively similar to that observed with either γ-aminobutyric acid or chloride ion and was partially reversed by the γ-aminobutyric acid receptor antagonist, bicuculline. In contrast to the effects of γ-aminobutyric acid and chloride, the enhanced binding of [3H]benzodiazepine elicited by Avermectin B1a was 

 reversed by extensive washing of the membrane preparation. Avermectin B1a appears to irreversibly modify benzodiazepine receptors at a γ-aminobutyric acid-chloride recognition site and may be valuable in biochemical studies of the regulation of benzodiazepine receptor function.

 

https://www.sciencedirect.com/science/article/abs/pii/0006291X80914023

 

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1471-4159.1982.tb08639.x

 

Abstract

Abstract: Avermectin B1a stimulates high-affinity binding of [3H]-γ-aminobutyric acid (GABA) to receptors in washed rat brain membranes. Scatchard analysis of the data indicates that the drug does not significantly alter the apparent dissociation constant of GABA binding, but increases the detectable number of binding sites from 3.2 to 5.1 pmol/mg protein

 

Found this searching over the internet, as it's what i have been doing, for reasons aside of the withdrawals but related, avermectin  it's a cousin of ivermectin, selecting who maybe feel interested, i dont know about the safety of the above one

 

https://www.mdpi.com/1467-3045/45/8/395

 

@[Na...], @[Ha...] @[4M...]

Edited January 16 by [De...]

[[Ha...]]

35 minutes ago, [[D...] said:

632-638

Avermectin B1a: An irreversible activator of the γ-aminobutyric acid-benzodiazepine-chloride-ionophore receptor complex

Avermectin B1a markedly increased the binding of [3H]diazepam to benzodiazepine receptors. This effect was qualitatively similar to that observed with either γ-aminobutyric acid or chloride ion and was partially reversed by the γ-aminobutyric acid receptor antagonist, bicuculline. In contrast to the effects of γ-aminobutyric acid and chloride, the enhanced binding of [3H]benzodiazepine elicited by Avermectin B1a was 

 reversed by extensive washing of the membrane preparation. Avermectin B1a appears to irreversibly modify benzodiazepine receptors at a γ-aminobutyric acid-chloride recognition site and may be valuable in biochemical studies of the regulation of benzodiazepine receptor function.

https://www.sciencedirect.com/science/article/abs/pii/0006291X80914023

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1471-4159.1982.tb08639.x

Abstract

Abstract: Avermectin B1a stimulates high-affinity binding of [3H]-γ-aminobutyric acid (GABA) to receptors in washed rat brain membranes. Scatchard analysis of the data indicates that the drug does not significantly alter the apparent dissociation constant of GABA binding, but increases the detectable number of binding sites from 3.2 to 5.1 pmol/mg protein

Found this searching over the internet, as it's what i have been doing, for reasons aside of the withdrawals but related, avermectin  it's a cousin of ivermectin, selecting who maybe feel interested, i dont know about the safety of the above one

https://www.mdpi.com/1467-3045/45/8/395

@[Na...], @[Ha...] @[4M...]

Naturally occurring in Brewers yeast and soil bacteria. Probably not in the amount used in the study however 

[[Ha...]]

Avermectins

The mode of action of avermectin B1a and ivermectin has been reviewed in [18,134,180–183]. Avermectin B1a and ivermectin are potent inhibitors of the neuromuscular transmission causing paralysis of the susceptible organisms [184–188]. These drugs appear to stimulate the release of GABA from nerve endings (GABA agonist) and enhance the binding of GABA to its post synaptic receptor. In other words, ivermectin mimics the action of the inhibitory neurotransmitter, GABA; this effect can be blocked by the GABA antagonist picrotoxin [184].

 

The paralysing action of ivermectin on the nematodes is due to its ability to activate a membrane chloride conductance in neurons of the nerve cord either directly or by enhancing the presynaptic release of GABA [180,189] which eventually results in opening of chloride channels.

https://www.sciencedirect.com/topics/chemistry/avermectin-b1a

 

The paralysing action doesn't sound ideal, but that was just a quick search. 

Edited January 16 by [Ha...]

[[Ha...]]

Conclusion: Ingestion of a large dose of avermectin may be associated with life-threatening coma, hypotension, and subsequent aspiration.

https://www.sciencedirect.com/science/article/abs/pii/S0196064499702714#:~:text=Conclusion%3A Ingestion of a large,%2C hypotension%2C and subsequent aspiration.

 

Think I'll give that 1 a miss

[[De...]]

 

1 hour ago, [[H...] said:

Conclusion: Ingestion of a large dose of avermectin may be associated with life-threatening coma, hypotension, and subsequent aspiration.

https://www.sciencedirect.com/science/article/abs/pii/S0196064499702714#:~:text=Conclusion%3A Ingestion of a large,%2C hypotension%2C and subsequent aspiration.

Think I'll give that 1 a miss

Hey @[Ha...] , i will take a look on that paper, but there are several kinds of avermectin, in this case is avermectin B1a

 

I guess those are suicide attempts, from the paper, Eighteen patients with abamectin (Agri-Mek; 2% wt/wt abamectin) exposure and 1 with ivermectin (Ivomec; 1% wt/vol ivermectin) ingestion were identified. 

 

I guess that abamectin has nothing to do with this particular compound avermectin b1a

 

i have been taking ivermectin, hopefully i wont get a setback, but taking for nerve regeneration and spinal cord that feels like lung cancer, taking 6mg then next day 3 mg, then 6 mg, so on, i Will take It for 5 days and cycle off, i took ivermectin posterior to my last withdrawal attempt without major issues at the time, i was under pregabalin and less damaged tho

 

 

Edited January 16 by [De...]

[[De...]]

abamectin consists of 80% or more of avermectin B1a and 20% or less of avermectin B1b and is called avermectin B1 (Fisher and Mrozik, 1989). 

 

Probably this ones mentioned are due to high dose poisoning, leading to bad outcomes

 

Avermectins are composed of four major components (A1a, A2a, B1a, and B2a), constituting more than 80% of their total composition, as well as four minor components (A1b, A2b, B1b, and B2b), which constitute less than 20% of their total composition. Among these eight components, it has been reported that avermectin B1a exhibits the lowest toxicity in animals and human beings 

From this study 

https://www.mdpi.com/1467-3045/45/8/395

 

 

Edited January 16 by [De...]

[[ns...]]

6 hours ago, [[D...] said:

632-638

Avermectin B1a: An irreversible activator of the γ-aminobutyric acid-benzodiazepine-chloride-ionophore receptor complex

Avermectin B1a markedly increased the binding of [3H]diazepam to benzodiazepine receptors. This effect was qualitatively similar to that observed with either γ-aminobutyric acid or chloride ion and was partially reversed by the γ-aminobutyric acid receptor antagonist, bicuculline. In contrast to the effects of γ-aminobutyric acid and chloride, the enhanced binding of [3H]benzodiazepine elicited by Avermectin B1a was 

 reversed by extensive washing of the membrane preparation. Avermectin B1a appears to irreversibly modify benzodiazepine receptors at a γ-aminobutyric acid-chloride recognition site and may be valuable in biochemical studies of the regulation of benzodiazepine receptor function.

https://www.sciencedirect.com/science/article/abs/pii/0006291X80914023

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1471-4159.1982.tb08639.x

Abstract

Abstract: Avermectin B1a stimulates high-affinity binding of [3H]-γ-aminobutyric acid (GABA) to receptors in washed rat brain membranes. Scatchard analysis of the data indicates that the drug does not significantly alter the apparent dissociation constant of GABA binding, but increases the detectable number of binding sites from 3.2 to 5.1 pmol/mg protein

Found this searching over the internet, as it's what i have been doing, for reasons aside of the withdrawals but related, avermectin  it's a cousin of ivermectin, selecting who maybe feel interested, i dont know about the safety of the above one

https://www.mdpi.com/1467-3045/45/8/395

@[Na...], @[Ha...] @[4M...]

Denitzthekid, my doc prescribed baclofen 5mg. I havent taken it yet. Uses to take it for trigeminal neuralgia. The more I read about it the more confused I get.  Seems on one hand it would be good for withdrawl of benzos and other drugs but on the other hand works on the gaba receptors in brain and gut. Not sure if this is good or bad. I asked him about broken because I took it in the past and knew it relaxed spasms etc, but I'm so hesitant to take anything that affects gaba, can't tell if it's a positive or negative fir those of us going thru benzo withdrawal 

Thought I'd ask u, maybe u can look into it, my brain is to fried right now to make sense of it all. There are several search engines for it. 

If u find anything on this, please let me know.

Hope your doing well, how's the thyroid testing going?

 

Baclofen also has important neuromodulatory effects in the amygdala, through its inhibitory action on neurotransmitters and complex effects on second-messenger signaling (37). It reduces the strength of excitatory (glutamate) and inhibitory (GABA) transmission in the amygdala by a presynaptic mechanism (131).Oct 17, 2018
https://www.ncbi.nlm.nih.gov › pmc
A Review of the Potential Mechanisms of Action of Baclofen ...

[[De...]]

@[ns...] not good Imo(i mean the bacoflen) idk about sporadic use, but def not good for everyday use , it has withdrawal symptoms, saw several stuck on it needing to taper and undergoing withdrawals,  go with meloxicam and pioglitazone instead, or nimodipine in low doses as It seems to help with TG pain

 

Edited January 17 by [De...]

[[ns...]]

Sorry to hear your not feeling well darn it!

Oh no I don't have that anymore, are you referring to the baclofen? Are u saying it's not good or is it something else your talking about? Research says baclofen depresses the cns like benzos but helps with withdrawal from certain drugs, agonist to the gaba b, brnzos affect gaba a, so I thought maybe it would help. The nerves in My belly are going crazy, we have gabs receptors in our gut. He thought this would help. They use it for esophagus spasms as well and acid reflux. Sooo. Just wondering if you were referring to the sane thing?

Pharmacy says it's great just maje me a little drowsy, who knows???

I know your not feing well so I won't keep bothering you with this ok, just knew you were goid at looking into these things

Take care now!

Ns

Edited January 16 by [ns...]
Additions and corrections

[[ns...]]

1 hour ago, [[D...] said:

@[ns...] not good Imo, idk about sporadic use, but def not good for everyday use and has withdrawal symptoms, saw several stuck on it needing to taper and undergoing withdrawals,  go with meloxicam and pioglitazone instead, or nimodipine in low doses as It seems to help with TG pain

Thanks Denizthekid, I'm going to take one and see how I do, if it helps I'll only use it sporadically for sure. Can't take most anything so who knows, I'll let you know how it goes!

Thank u fir your input, I appreciate it! 

You take care of yourself ok 

By for now

[[Be...]]

5 hours ago, [[n...] said:

Denitzthekid, my doc prescribed baclofen 5mg. I havent taken it yet. Uses to take it for trigeminal neuralgia. The more I read about it the more confused I get.  Seems on one hand it would be good for withdrawl of benzos and other drugs but on the other hand works on the gaba receptors in brain and gut. Not sure if this is good or bad. I asked him about broken because I took it in the past and knew it relaxed spasms etc, but I'm so hesitant to take anything that affects gaba, can't tell if it's a positive or negative fir those of us going thru benzo withdrawal 

 

I took Baclofen 10 mg after jumping from diazepam. It's okay, as long as you don't take doses higher than 10 mg, and no longer than 2 months. After 2 months, you have a greater risk of dependency, and then you have to taper off of it just like benzo's. I was able to stop it completely at the end of 2 months, with no issues. It helped me get some sleep during acute, but I did jump from 2.75 mg of diazepam using NAD+ as an assist. So, my acute was pretty intense. I found out about in a post on Reddit where a lady was asking about it, as she was about to do IV NAD+, and she was prescribed 10 mg post NAD+ for 2 months. She was concerned about it being a potential problem. It just really helped my body to relax, and enabled me to somewhat sleep without shifting around in bed. 

[[ns...]]

8 minutes ago, [[B...] said:

I took Baclofen 10 mg after jumping from diazepam. It's okay, as long as you don't take doses higher than 10 mg, and no longer than 2 months. After 2 months, you have a greater risk of dependency, and then you have to taper off of it just like benzo's. I was able to stop it completely at the end of 2 months, with no issues. It helped me get some sleep during acute, but I did jump from 2.75 mg of diazepam using NAD+ as an assist. So, my acute was pretty intense. I found out about in a post on Reddit where a lady was asking about it, as she was about to do IV NAD+, and she was prescribed 10 mg post NAD+ for 2 months. She was concerned about it being a potential problem. It just really helped my body to relax, and enabled me to somewhat sleep without shifting around in bed. 

Benzolottie,

Thank u! Just took 5mg of baclofen,  but I'm still tapering 1mg lorazapam split into 4 doses. I tried to lower it twice but no go!!! O had to start tapering due to paradoxical reaction i think, the lorazapam did a reverse on me and gave me extreme anxiety and panic attacks. Strange,! So.im tapering a medication that is hurting me, but i have no choice but to taper. I've gone pretty fast,  probably way too fast but these are killing me.

I used to take baclofen 10mg, they helped with spastic colon, trigeminal neuralgia and muscle spasms. So I asked my doctor and he agreed. He knows I'm tapering. I do feel a little heavy, the gaba receptors in my belly (nerves) are going crazy for a week making it hard for me to stand and walk. I have involuntary body jerking and losing coordination. 

Boy I hope these help, I'm getting exhausted, stinging like bees all over my body and face. So far no relief. I guess it'll take time. I'll try another in the am about 7am. Don't want to take it to close to.my lorazapam dose. I am sensitive to just about every medication so I'm hoping these will help.

I'm so grateful to you for messaging me with a good report on these baclofen,  I've heard you go into tolerance pretty quickly so if they help. I won't stay on them. If they help me. I'll use them to go off the lorazapam! 

OK, I've bent your ear,

Better go now

Again,  thanks so much

That really makes me feel better!

By for now 

Ns