What Causes Alcohol Poisoning?

[LandsUnknown]

Obviously, too much alcohol. However, I know that alcohol raises gaba, and I have been told that this is the primary cause of drunkenness. However, it is relatively easy to overdose on alcohol conpared to many substances. Despite this, oddly enough I have heard that it is difficult to overdose on gabapentin and some other gaba active drugs. So, what is it exactly about alcohol that makes alcohol poisoning a surprisingly common event in comparison to many other drugs? Since apparently there are other gaba active drugs that are relatively non toxic, such as phenibut and gabapentin. Yet alcohol is toxic to thr body, but what about it causes the side effects (e.g. bad for the liver, nausea, spins, overdose potential, etc.)

 

[polymath]

I think gabapentin/pregabalin affect some other ion channels, not the GABA-A receptor (of course they may indirectly increase GABAergic activity by some mechanism). Ethanol, barbiturates and benzodiazepines act by potentiating the effect of your body's own GABA on the receptors, while the muscimol in amanita muscaria mushrooms activates the GABA-A receptor directly. As you know, ethanol and barbiturates have a very low therapeutic index unlike the benzodiazepines (not sure about the neurosteroid GABAergics which is another class), so there are differences in the effects of these positive allosteric modulators of GABA.

 

[Limpet_Chicken]

Polymath-barbs (and by extension other barb/picrotoxin site ligands with similar channel-gating kinetics) DON'T require GABA binding.

Benzodiazepines bind to GABAaRs bound by GABA, and via the allosteric interaction of classic benzos (disregarding the oddballs like KOR agonists etc) increase the effect of GABA, but in the absence of GABA, do not directly, unlike barbs, chlormethiazole etc. induce channel opening, whilst barbiturates and the like can directly induce channel opening and induce chloride flux all on their own. Which is part of what makes them dangerous. In the case of a ligand acting to make the effects of GABA more profound, then the body can compensate via lowering GABA release. In the case of a ligand which directly opens the chloride channel, it can't.

 

[polymath]

Sorry for the partially wrong information. Anyway, I guess an answer to the original question is that the kind of GABA-A receptors (composed of the correct set of subunits) that are most strongly affected by benzodiazepines don't exist at a very high density in the regions of brain that control respiration or other vital functions, hence it's difficult to overdose on benzos.

 

[Limpet_Chicken]

Aren't most of the benzo sensitive GABAaRs also barb sensitive? its less a matter of capability to bind and much more what they do when they get there.


(disclaimer-currently being typed under the influence of 9 or so of those little grey heminevrin eggs and with 5mg nitrazepam kicking in too) (no-don't DO that folk. I am and always have been damn difficult to sedate)

(chlormethiazole is like a barb sans AMPA antagonism. IMO the AMPAr blockade of barbs is responsible for their fuzzy and sloppy effects, which are rather absent from chlormethiazole. That would, blocking a major excitatory fast postsynaptic transmission system whilst also directly facilitating the inhibitory neurotransmitter sine qua non in the brain adds even more danger to ODs. I KNOW my limits with chlormethiazole+benzos, the second of these I use parsimoniously in terms of dose frequency. Whilst ignoring the longterm tolerance built up to opioids always present, as a chronic pain patient, and I have always been what is often referred to as hard-headed for such drugs as benzos in the extreme, when used on their own, that is, at a minimal level to prevent WD for anaesthetic induction, there does need to be at least the minimum quantity required to be well.)

But, my head has always been a very tough nut indeed with regard to dosages. Even 5-10mg nitrazepam (edit, that should have been 70 or 70x2) guess it got to me a bit when it came to math skills that weren't there to begin with) along with 8-9x192mg chlormethiazole has had instances where I've remained very, very awake.

 

[busted.produk]

Ethanol produces toxic metabolites....

 

[brexit]

[FONT=q_serif]Pretty bad. Unable to hold up your own head, constant vomiting and feelings of regret and misery. You'll feel even worse the next day too. Headaches, vomiting, you name it. It all adds up to the hangover of a lifetime.[/FONT]

 

[Limpet_Chicken]

Pretty much. My ONLY uses for it, are in either beer or cherry wine, in which case I look at it more as a byproduct of fermentation, or as a drug for short-term sedation when a guaranteed knockout is needed. I don't drink weekly, but my typical use would be in the last hour or so before I'm due to pick up a pain med script. Because then I'm going to feel shitty, sore and like eating the next person to cross my path.

Its only any use as a stopgap measure, depending on whether or not the damn doctors decide one week or another to fuck about with my usual anticonvulsant measure (chlormethiazole, occasionally nitrazepam, if the latter proves too short acting despite repeat doses to actually sleep safely, given coming out of sleep is usually when its going to hit, or hit first and worst if its just going to be one of those days). Nuke a couple of hours into last week is about all its fit for. That and as a solvent for Beauveault-blanc (sorry, I probably mangled that spelling, its a bugger, sue me) reductions of oximes to amines. Otherwise I don't want it anywhere near me unless I have a specific need for either an ethoxide, or ethyl halide, or ether (although I'd sooner use the sulfuric condensation route if I had to MAKE the latter)

Nothing worse than hangovers..booze seems to produce the worst of the lot, as far as recreational substances go, unless your going to bugger about with something like paraldehyde, chloral, chlorobutanol or GHB. Ew. Now even the smell of acetaldehyde...faint, horrid...like acetone if it gave birth to rotting fruit...christ...Give me some stinky ass sulfur horror any day, over that (within limits)

 

[clubcard]

It is interesting that an α5β1 selective benzodiazepine fully substitutes in alcohol-dependent users and the subjective effects seem to be mediated entirely through this very specific site. I can't see it ever becoming a legal replacment in my lifetime but maybe in the lifetime of many people here. Ethanol is just one member of a class that includes members beyond tert-amyl alcohol. I suppose someone could take and write a commentary of each member of the class for future 'explorers' but it don't think I would be too keen.

People have mentioned drugs with similar activity profiles but about the only other place to look for potential alcohol-like activity are the α5β2 & α5β3 subunits. They may well be where Nutt is hunting. It has gone quiet but he knows his work. I, for one, would be pleased as punch if I could buy one of those big cans of 'energy drinks' that had such compounds rather than caffeine in them. Being blind drunk and waking up feeling utterly fine is possible something to make it a more insidiously dependence-forming drug thus partial agonists are a better move? Who knows.