Its sort of hard to tell which is which when both are active. Although I vastly prefer chlormethiazole to benzos, due to its barbiturate-like action. Quite surprised I got it prescribed for seizures, and other medics such as in hospital or ambulances if I've needed one, like I did with some heart problems the other week (a sinus tachyarrhythmia). Its usually used for in-patient alcohol detox here. But for whatever reason, the GP agreed to my request to use it for the seizures, because I've had it before in the past, and knew it to be both very, very, very rapid acting (it'll stop a seizure in its tracks within minutes of getting a warm feeling in my throat as the capsules burst. So fast in fact that if I'd have seen it in someone else, I'd have thought 'placebo, they couldn't possibly have released their contents that fast surely..' but no, it has an onset more like something in the way of strong alcoholic spirits, although I'm not much of a drinker, something like azeotropic ethanol, diluted to 80% or so with some elderflower cordial and cold water and washed down with more soft drink or beer, that'll knock one out completely within minutes, and chlormethiazole has a a similar rapidity of onset. I like it, particularly for speed of onset, also for the fact that it really does, reliably, do what it says on the tin. And if a little extra happens to crawl out of a flask via vitamin B1 cleavage, removal of the toxic convulsant poison, toxopyrimidine, a vitamin B6 antagonist that blocks GABA biosynthesis and then goes to take a bath in thionyl chloride, who am I to tell it, sorry, not recreational enough for me, go back where you came from and thanks a bunch for wasting my SOCl2 or if experimenting, perhaps PCl3 once I get round to making more of the latter halogenating agent.
The main reason I've been wanting to ask the question of others here (and here's another one for you guys)
I've found that chlormethiazole seems to produce no physical dependence (at all) in me, I've not pushed it super extreme, but I do take it three times a day, plus rescue-packs to deal with seizures that do get through, although generally just taking a dose of opioid, a shot of morphine or a couple of oxy IR capsules broken open and the contents insufflated, or else just smoking a foil of H, all seem incredibly effective. Indeed, as a last-ditch effort, after I'd started having a seizure but it had started myoclonic rather than going through a paralytic stage first, and I just about managed to grab hold of a foil with a pre-melted (so I couldn't just throw it all in my face, etc. when my arms refuse not to stop jerking uncontrollably, etc.) blob of H, some nice light tan, pretty strong stuff, was the morning I was due to pick up refills for all my meds, so everything was at the lowest possible plasma level, opioid aside since I had the H to get me through the weekend, anyhow, shaking and twitching, got the lighter in one death-gripping fist and a straw in my mouth, you don't need me to explain the rest.
Other than that after the first toke, the intensity of the attack really calmed down, and after the second, third, a few more big long omg-my-lungs-are-gonna-burst! sort of hits, held in as long as possible before blowing the exit vapors into a cold test tube on the walls through the straw to recondense as much as possible and recycle. The attack subsided, totally, and although they would have restarted within not very long if I'd gone to sleep, I wanted to test it, so I did go back to sleep after finishing the foil of H.
Completely killed the seizure, and they didn't return until the H had worn off.
Anyway, back to the chlormethiazole, what I don't get, is how I can keep using it, a powerful GABAergic depressant, a lot more powerful than any benzo will ever be, for years, several times a day, every day, without physical dependence.
Had I used a benzo, any of them, once a day every day I bet I'd be physically dependent to some degree within a month to a couple of months at most with real low doses of an intermediate acting one which wouldn't build up in plasma. I'd be in shit city.
But with chlormethiazole, the only events that affect me if I were to suddenly not take it, would be that I have more seizures, because the coverage of meds is removed and I'm back to square one, no withdrawal symptoms, no anxiety other than when realizing that I have forgot to take them, and thats just situational anxiety, about being more vulnerable to seizures rather than drug withdrawal constant, unrelenting anxiety over everything and anything or nothing at all. But otherwise, nothing. And as soon as I've got the bottle in my hand, or remember and start going to wherever it is, to take what was forgotten, any such anxiety
just disappears, before I've actually got there or taken the drug. Any ideas why it might be so un-prone to causing physical dependence?
Barbs themselves do, but this is made more complicated by the fact that they are also AMPA receptor antagonists or negative allosteric modulators. So, with a pure barbiturate site agonist at GABAa, like chlormethiazole, at least where glutamate and GABA receptors are concerned, might the fact that receptors desensitizing towards GABA, like they would as a compensatory mechanism behind benzo tolerance, among others, the fact that a barb type agonist can directly gate the chloride channel in the absence of GABA would prevent desensitization from doing very much about it. Although they don't seem to have done much of anything in terms of tolerance, well, I can tolerate the drug better, and take somewhat larger doses, than I would had I no experience of using the stuff and not the knowledge of how my body responds to it, and being settled in to using my pain meds.
Quite an oddball of a drug, chlormethiazole is, and its brominated relative, not that I'd want to do more than test the latter, given the potential as a leaving group for the halide, so not one I'll be using regularly. And I'm skipping the iodo homolog completely because iodide is just too good of a leaving group. Although cyano and nitro are interesting, maybe pentafluorosulfanyl, before moving on to oxazole homologs. Definitely an oddball, though, alone it's category, very, very easy to make as long as one removes the convulsant poison byproduct from the intermediate methylthiazole-2-ethanol when it is prepared, one of the very few barbiturate-esque drugs dripping with abuse and recreational potential like a whore's cunt at a frat party; and with pretty fine potency, not too much, not so potent as to be dangerous to physically handle without ingestion but just right IMO. Eats plastics so is unsuited for people trying to IV the oily freebase, and lipophilic enough to hit really fast indeed orally or plugged in an oily dispersion with something like olive oil, although even orally its active in minutes, after the capsule releases its contents.
And has a really odd lack of tendency, when used several times daily, at medical purposes doses, to cause physical addiction, at least in me, not even when the dose has had to be increased for a while when needing rescue packs for the seizures.
I can't dismiss it as some autie quirk, so anybody have any ideas why this drug seems so non-dependence prone? its the last thing I'd expect from a GABAa agonist ligand with a barb-like pharmacological profile. As I said, had it been either barb or benzo, or something like ethchlorvynol, methaqualone I know damn well I'd not have had a cat in hell's chance of getting away without dependency. And not taking years, taking a couple of months at the very most. Not counting really mild, mild herbs like lemon balm tea with its GABA-transaminase inhibitor effect, or relaxants like lavender oil in aromatherapy, that sort of thing, even valerian might grow a set of teeth if it were hammered for a while, not that I'm about to try it to see if I can find out if it does just for the fuck of it, I prefer to avoid misery if I can help it. And especially given if the worst happened and I ended up in hospital, it isn't as if the medical system even HAS a loreclezole site agonist to use for detox. And for that matter they'd probably laugh at the idea of addiction to a herb, unless its cocaine from coca or opium poppy, if they haven't heard of it and it isn't infamous then they probably would be too concerned taking the piss to assist a patient with such an issue.
So..whats with the stuff, and tolerance (to it alone, I mean, rather than crosstolerance) ? it displays some very unusual behaviour for a GABAa agonist, especially a hard-hitter and potent ligand such as chlormethiazole. Weird, weird stuff. Acts as funky as it smells.
And although unrelated to the thread title, how about opioids as antiseizure meds. I mean, rather than suggesting people do that, whats with that, just general increased inhibitory tone across the brain? would make sense I suppose. But damn, it isn't half effective, in my case, using an opioid, its like throwing a kill-switch and disconnecting the power supply to the electrical storm, symptoms just vanish, even with only a small dose (say, 20mg insufflated oxy, whilst I'm taking 80 a day usually at least