#GABA receptors

[er-cryptid]

[danielradcliff]

there are several negative things about taking adderall many days in a row to study for the exam but the worst part is that I can FEEL it becoming less effective

[angelstrawbabie420]

u ever seriously wonder if ur gonna make it thru the year

[spencereid]

took my anti anxiety meds instead of powering thru it!!!! yay!!!!

[yardsards]

idk about benadryl but i have a response like that to benzodiazepines and apparently when that happens it's got something to do with the GABA receptors being weird, so maybe it's similar?

oh, neat!

[stressfulsloth]

Sorry, I'm still on this. It's funny to me. And by funny I mean really sad actually. That it's always bisexual characters whose sexuality gets viewed as "up for debate." Like you have Harry Du Bois, a character who clearly expresses his attraction to his ex wife, who can ask Klaasje to "have fuck" with him within the first five minutes of the game, who is attracted to Joyce and keen to go on a date with Lilienne, but who ALSO gets flustered over the smoker on the balcony and his unbuttoned shirt ("he smells good. Why does he smell good?"), who fixates on impressing Tommy le Homme, who smells Kim's cologne and immediately calms down ("GABA receptors aflutter"). The "thrashed like a school boy" line. The "preferably a large man dressed in nothing but a towel, to thrash you while you're spread naked and helpless on a cool slab" line. The whole "bi-curious" conversation. The "it's good, but I'd prefer a man. A solid muscularity would support me better" line. The "muscles, I said muscles! I want manly-manly muscles". The line suggesting Harry's familiarity with bottoming?? ("Not many people know that. But you do. Go figure.") The way that sexuality interacts with class and expectations of masculinity and how that ties in perfectly with the games overarching themes, with the hope and the fear of the world surrounding him.

And even with all of that, somehow, it's apparently still up for debate.

[heysawbones]

Let's Talk about Xyrem.

Xyrem ("oral sodium oxybate" or the sodium salt of gamma-hydroxybutyrate) is used in the treatment of narcolepsy, as well as (sometimes) idiopathic hypersomnia. Even if you don't have narcolepsy or any related conditions, you may find this run-down interesting. Here's why:

Gamma-hydroxybutyrate is roofies. That's right. Date rape drug. Right here.

The drug is so tightly controlled that there is one pharmacy in all of the United States that can fill it. Doctors must be approved and participate in a special program to even prescribe it.

Nobody really knows how it works in the treatment of narcolepsy.

I was prescribed Xyrem quite some time ago - at this point, nearly a year back. It took six-plus months of insurance, doctor's office, and central pharmacy wrangling to get the drug to my door. The whole time, I wondered: what should I expect from Xyrem? How do I know if it's working? How do I know if it's not working? What's it like? Lists of side effects and contraindications are readily available online, but I couldn't find a single detailed testimonial. This bothered me.

I've been on Xyrem for about a month and a half now. Here's what I can tell you about it.

You have to wake up at night to take a drug that's meant to improve your sleep. Everybody I explained this to found it funny. The standard practice is to split your dose in two - to take one half at bed, and the other half two to four hours later. If you're on Jazz Pharmaceuticals brand Xyrem and not the generic, they send you a tiny little alarm clock with a light on it to facilitate this. I have never needed it.

It takes 3 weeks to titrate up to the "full" dose, which is also the maximum dose. From there, you can titrate back down to a lower dose if you're experiencing unpleasant side effects. I'm in the process of doing this myself.

It doesn't necessarily knock you out. From the way the drug is described, one might get the impression that the moment it kicks in, you're going to be unconscious. I didn't find this to be the case. Your mileage may vary; I don't always fall asleep at all on the first dose, but it does at least get me sleepy enough to fall asleep on the second.

You have an unusual amount of agency in how you take Xyrem. This surprised me, especially given how tightly controlled possession of this drug is. For example, I metabolize Xyrem really fast. If I take it in two doses, I will sleep a maximum of 6 hours. I take the same amount of medicine and split it into three doses instead to compensate for how fast I metabolize it. That way, I'm more likely to sleep about 8 hours. This isn't just accepted, it's encouraged. You can even take a bigger dose first and a smaller one second, or vice-versa. The only hard and fast rule is: do not go over the max dose.

If you take it with alcohol, or within 4-6 hours of alcohol, it could kill you. A lot of drugs warn you not to take them with alcohol. I cannot stress enough that if you have ignored that warning in the past: do not ignore it here. Do not. Xyrem is a powerful CNS depressant. Alcohol is a CNS depressant. It really can kill you.

It works(?) Like many drugs that act on the brain, nobody is really sure how Xyrem works. It doesn't affect the most common (known) cause of narcolepsy (a lack of orexin/hypocretin). It's theorized that the drug acts on GABA receptors in a way that "consolidates" the fragmented sleep architecture of narcolepsy.

Narcolepsy can be thought of as an autoimmune disorder of sleep architecture. The sleep architecture of a narcoleptic is irregular, both within itself and from night to night. People with narcolepsy tend to have less of the deep sleep stages than they should. Narcoleptics also have a high percentage of stage 1 (light) and REM sleep. It's theorized that excessive REM occurs because it is of poor quality/does not serve its intended function, so the brain spams REM in an attempt to compensate. A diagnostic trait of narcolepsy is the ability to enter REM within 8 minutes of falling asleep - if sleep architecture is normal, this does not occur. While not all people with narcolepsy have cataplexy, cataplexy itself is actually REM intrusion into waking life. The narcoleptic brain is that screwed up about REM. Xyrem appears to regulate shifts between sleep stages and reduce the nightly percentage of REM sleep. I used to dream nightly. Subjectively, I do not dream at all on Xyrem.

The only difference between Xyrem and Xywav is salt. A full 9g dose of Xyrem contains 1,640mg of sodium. The maximum sodium intake recommended by the American Heart Association is 2,300mg. One of the few things I saw said about Xyrem prior to taking it was that it was disgustingly salty. It is very, very salty. I don't mind it, though. I've seen it said that Xywav tastes much worse, but I can't attest to that.

Subjective experience

Xyrem comes Priority Air Mail in a sizable cardboard box. An adult with ID must be present to sign for it. The first month's prescription comes with a light-up alarm clock. This kit and all subsequent kits come with:

The medicine, in however many bottles are required

A number of syringes, marked with common doses

A number of pill bottles

You put water in the pill bottles. They tell you to put about 60ml, but as far as I can tell, this is to make the saltiness tolerable. I made a little game of this - I try to put the same amount of water in each pill bottle, gauged by nothing but sound. I've gotten pretty good at this. I have my nightly dose split 3 ways. After adding the drug to the water, I close each bottle and swirl it a bit. I don't know if this actually does anything.

Xyrem works best if you're already tired when you take it. Hilariously, I have ADHD in addition to narcolepsy. Nighttime sleepiness isn't a thing I Do naturally. Consequently, the first dose of Xyrem only puts me to sleep about half the time, and it takes a while even when it does. I know myself well enough to know that if I wait until I'm actually "sleep for the night" tired to take it, I might be up until 3 or 4 AM. Instead, I take the first dose at around 11 PM. Even if it doesn't put me to sleep, it DOES make me sleepy enough that the dose I take 2-3 hours later will definitely work.

I was very careful to set alarms the first week or so of taking Xyrem, but I've never needed them. For reasons that are unclear to me, I always wake up when Xyrem is fully metabolized. Without more Xyrem, there is no urge to go back to sleep. When I've run out of doses for the night, I'm up for the rest of the day. There's no napping.

Some people have pretty nasty side effects with Xyrem. Headache and nausea are the most common. I had both of those, once each. The headache lasted all day but was otherwise unremarkable; the nausea was genuinely awful. The only persistent side effect I have, is tremors.

While I was waiting for Xyrem, my sleep specialist put me on Adderall. Nobody would prescribe this for ADHD, but you'll do it for narcolepsy? Sure, whatever I'll take it. I mention this because I thought it was possible that Adderall was causing tremors. I ran a little experiment: I took Xyrem but no Adderall one day and still had tremors. I took Adderall, but no Xyrem the night before, and the tremors subsided. It's definitely the Xyrem. While this is a known possible side effect, I can't find any information on how or why Xyrem, a CNS depressant, would cause something that seems very much the opposite of a depressed central nervous system. I am currently titrating back down from the max dose in an attempt to see if a lower dose will mitigate the tremors. If that doesn't work, I'm not... entirely sure what to do. Xyrem is a weird drug. It's strange not to dream at all; it's strange to wake up twice a night and still get better sleep than I ever have. Executive function has improved considerably, given that both neurological issues that cause executive dysfunction are being treated. Still: the tremors are, I will not lie, distressing. Not as bad as they were on Wellbutrin, which I was forced to discontinue! But - disruptive and distressing, nonetheless. I'm hoping that the tremors will stop eventually, or that dose adjustment will help.

Overall: would recommend if you have narcolepsy. You wouldn't think that a drug that obligates you to wake up multiple times a night could improve your sleep! Well, bucko, if your sleep architecture is already so disordered that you have narcolepsy: it can.

[e2019]

Abstract

Tramadol overdose is frequently associated with the onset of seizures, usually considered as serotonin syndrome manifestations. Recently, the serotoninergic mechanism of tramadol-attributed seizures has been questioned. This study’s aim was to identify the mechanisms involved in tramadol-induced seizures in overdose in rats. The investigations included (1) the effects of specific pretreatments on tramadol-induced seizure onset and brain monoamine concentrations, (2) the interaction between tramadol and γ-aminobutyric acid (GABA)A receptors in vivo in the brain using positron emission tomography (PET) imaging and 11C-flumazenil. Diazepam abolished tramadol-induced seizures, in contrast to naloxone, cyproheptadine and fexofenadine pretreatments. Despite seizure abolishment, diazepam significantly enhanced tramadol-induced increase in the brain serotonin (p < 0.01), histamine (p < 0.01), dopamine (p < 0.05) and norepinephrine (p < 0.05). No displacement of 11C-flumazenil brain kinetics was observed following tramadol administration in contrast to diazepam, suggesting that the observed interaction was not related to a competitive mechanism between tramadol and flumazenil at the benzodiazepine-binding site. Our findings do not support the involvement of serotoninergic, histaminergic, dopaminergic, norepinephrine or opioidergic pathways in tramadol-induced seizures in overdose, but they strongly suggest a tramadol-induced allosteric change of the benzodiazepine-binding site of GABAA receptors. Management of tramadol-poisoned patients should take into account that tramadol-induced seizures are mainly related to a GABAergic pathway. Keywords: GABA, overdose, positron emission tomography, seizure, tramadol

[drdemonprince]

sitting on a cement parking structure eating chips and 9 hours old juevos rancheros waiting for the bus and a woman recognized me and wanted to talk about GABA receptor autism treatment

[anotherobeymeblog]

Has anyone tried to figure out how demonus works biologically? The only thing I can think of is that demons have a fundamentally different brain structure, but because I'm both a nerd and a neuroscience student, I want to know how. I can think of two possibilities, but please share if you have any of your own!

So, real quick, here's a (very simplified) rundown of how alcohol works in the human body. The actual effective part of alcoholic drinks is called ethanol. (There are actually many types of alcohol, but ethanol is what people generally are referring to when talking about alcohol. This will be important later.) Ethanol is able to dissolve in both fat and water, which makes it very easy to travel around the body. It enters the bloodstream largely via the stomach and small intestine, and eventually crosses the blood-brain barrier into the... well, brain. Inside the brain are GABA receptors, which help to regulate brain activity by blocking neural signaling. Ethanol binds to these receptors, which basically sends them into overdrive and causes brain activity to slow significantly.

Now, I don't remember if the game ever specified whether human alcohol affects demons, which would have a huge impact on what demonus is. (We also don't have much information on how demonus tastes, which would be another clue) So, I have two theories, one for if human alcohol does affect demons and one for if it doesn't.

If human alcohol DOES affect demons, then that at the very least means that demons have GABA receptors (or a modified version of them). Ethanol is a very small molecule, which makes it easy for it to bypass fatty membranes such as the blood-brain barrier. An alcohol with a larger molecular structure would be more hydrophobic, so it would have a harder time crossing that barrier. Perhaps demons have a more easily permeable blood-brain barrier, so alcohols with larger molecular structures would be able to affect them, but when consumed by humans, less of it would cross that barrier. (Unfortunately, many alcohols will kill you very quickly, and we know demonus isn't lethal to humans, so that limits our options.) An example of a potential active ingredient in demonus is 2-nonanol, which is a much larger molecule than ethanol and has relatively low toxicity. (It's actually commonly used as artificial cucumber flavouring!)

If human alcohol DOES NOT affect demons, then things get trickier because we now know that they don't have GABA receptors, and therefore probably have a totally different brain structure altogether. At that point, it's hard to speculate as to what it actually is since we don't have much to narrow it down with. It's probably not something frequently seen in food (in high concentrations, at least), since we don't see demons getting drunk on human world food, and as said before, it's not something that is toxic to humans, but that's still too open-ended to speculate any further. At that point, it seems more likely that it's just some weird magic shit with no biological explanation at all, which is probably how it was intended to be interpreted in the first place.

[scoutpologist]

electrochemistry is such a horny bitch what the fuck do you mean the scent of kim's aftershave sent your "GABA-receptors aflutter" calm the fuck DOWN

[danielradcliff]

it’s important to gameify extended periods of studying as it’s the only way you can survive multiple weeks of insane hours. and by gameify, of course, I mean combine so many uppers and downers I get brain damage

[leechs]

What's a good drug to replace alcohol with? I'm a very severe alcoholic and have to drink 1l of vodka and 1l of wine pretty much every single day at this point. It's not fun and I feel like I'm a walking corpse. I live in a place where even cannabis is fully illegal. I thought about getting unwashed poppy seeds and brewing tea with them because apparently they have small amounts of opium on them. Have you ever tried this or know of anyone having tried this?

poppy seeds arent going to do anything for alcohol withdrawal because they work on opi receptors and alcohol is a central nervous system depressant that works on gaba receptors… if you really want to get off alcohol i would first start tapering your daily use slowly and then switch to xanax or another drug that works on gaba receptors as a way to transition off it… unfortunately alcohol is probably the worst drug to be physically dependent on because there is no getting around the symptoms of withdrawal and you can literally die if you go cold turkey… be careful

[sybaritick]

⭐ for tephra year or that urge often miscalled free will (or both, if you're so inclined!)

yessss!! <3 thank you i appreciate it esp for those two fics :3

i'll go for that urge often miscalled free will: i am a biotech nerd despite also being a total layperson and that means things like Gortash's offhand/worldbuilding comment on which neurotransmitters are targeted by which medications was just conveniently remembered from an article I read a couple years ago, Know Your GABA-A Receptor Subunits.

so even though it's very likely that some of the silly technobabble i throw into my fics for fun is not fully correct, it's also always written with the intention of being vaguely scientifically plausible: for example, Gortash's excuse for most of the modifications is that he thinks he can improve Gale's reaction time by replacing nerve-transmitted signals with electrically-transmitted ones. The idea that the nerve transmission is "slow" compared to what a machine is capable of is real!

and since i'm just bragging at this point a silly fun fact about me is i'm technically published/listed as an author in a paper in the journal of immunology even tho i was truly just a lab assistant/intern for a summer. not going to doxx myself or anything (and my birth name!) so i'm not posting that, but i'm like. layperson but unusually passionate layperson [sideeye] it is my duty and my privilege to misuse biology knowledge for irresponsible ends

[catboybiologist]

Why does opium make me feel so good

Opiates are a well characterized addiction model.

When neurons transmit an electrical signal to the end of their cell, they need to make that signal jump to the next cell. They accomplish this with neurotransmitters. These neurotransmitters open channels in the next cell which generally start a new signal (excitatory synapse). Alternatively, they can open channels in the next cell that reduce the likelihood that it will generate a signal from another source (inhibitory synapse).

Opiates have an insane array of effects across the central (brain and spinal chord) and peripheral (smaller sensory, motor, and all other neurons) nervous systems, each one eliciting a form of addiction. But the pain pathway is probably the easiest to understand.

Among those other effects, opiates mimic an inhibitory neurotransmitter in the peripheral nervous system, GABA. GABA is a neurotransmitter with many functions, but the important one here is that it functions as an inhibitory neuron to keep your pain receptors from firing too much.

Your body constantly retunes this to ensure you're at the right balance of pain reception to keep you out of danger without debilitating you based on pain sensation alone.

So you use opiates. And your body suppress more pain than usual. And it feels good. And then your body says "wait, no, this isn't right, we must be missing out on something" and retunes itself to need more inhibitory neurotransmitter (GABA or an opiate) in those neurons to actually have it's likelihood of firing suppressed. So you use more opiates to achieve the same effect. And on and on in a loop.

There's so much about opiate addiction not included here, but this is the simplest, cleanest molecular effect it has, among so, so many others in the brain and periphery nervous system.