What's going on with mGlu 5 antagonists?

[Solipsis]

Like MPEP, MTEP and Fenobam...

Are they not even taking these to clinical trials out of concerns for addiction potential or psychotomimetic potential?

What about the toxicology and have there been any experience reports whatsoever?

 

[sekio]

Apparently models showed fenobam was likely to have side effects at the same dose level it's efficacious at... anxiolytics are no good if they act as amnesic agents.

 

[Neithman]

nevertheless a very interesting compound,i wonder if there is a comparable amount of tolerance building and withdrawal compared to benzos

 

[DotChem]

yes as @sekio said apparently they're amnesics and unlike scopolamine type cholinergics amnesics, impairment (in rats at least) seems to be irreversible..rats pups treated with mGluR5 antagonists won't remember his own mother! .. I would stay away from these molecules until more is known ..

 

[bindingaffinity]

Basimglurant, at least, did make it to phase II trials for Fragile X and depression, but was stopped due to ineffectivity.

Dipraglurant has also made it to trials for dystonia. It is in phase II trials for levodopa-induced dystonia in Parkinsons disease and phase I trials for cervical dystonia.

These two aren't that structurally different from MTEP and MPEP, dipraglurant especially, so I hope that we don't find out they have horrible irreversible side effects in human trials. But I assume based on the fact that phase II trials were conducted without much fanfare that we don't have a BIA 10-2474 situation on our hands.

 

[clubcard]

Has anyone else noticed that EVERY centrally acting agent is studied as a neuroprotective? Soon this class will become orphan drugs. If you like swallowing random stuff, shop at Tocris. McN 5652 has all of the hallmarks of something Dr. Dave would play with. I did the aminorex QSAR so that's on some file in his lab... and won't end up in print.

 

[sekio]

If you like swallowing random stuff, shop at Tocris.

This would make good advertising press for a rc store

 

[Limpet_Chicken]

With regards to rat PUPS specifically...that could be important. Neonatal animals need strictly organized sets and waves of signalling processes to take place in the right place, right time, right order etc.

Fucking around with the primary excitatory neurotransmitter at such a time, it sounds pretty much like its asking for disruption of eventual neurological architecture in some way or another. It would be telling to see if the same happens in adults. Not that I agree, admittedly, with animal testing.

 

[clubcard]

This would make good advertising press for a rc store

Thanks for that - I just laughed Chocomel down my nose... 'De Enige Echte' ;-)

While I abhor animal testing, if you have something truly novel, potential harm needs to be tested for and you would need quite a lot of people to take part in what must by definition be an unofficial trial. Getting those licenses is a nightmare but I believe animal models are more or less a requirement. Reduce, Refine, Replace.

 

[Limpet_Chicken]

At least I'm not the only one. Although I narrowly managed to avoid dousing my laptop keyboard and screen in a mixture of bitter lemon, chlormethiazole and nasal mucus. I almost inhaled my anti-seizure meds, thanks sekio

 

[clubcard]

You sure like your clomethiazole. I guess alcohol is MUCH worse but all I can clearly remember was the TASTE. Sour apples mixed with chloroform, yum. All we need is for someone to cough their eyeball into their ear and we have a full set :D

 

[Limpet_Chicken]

Well, I guess I can own up to finding it an alright kinda drug. Sour applies mixed with chloroform? I thought I was the only one to think along those lines. Although for me its a hint of overripe apple mixed with a hint of mint, with some ether and undertones of hot steel, like you get from using a grinding wheel to shape hardened steel when it gets hot and starts to smoke.

I actually quite like the scent of chlormethiazole though, it isn't unpleasant, just different. Actually, I make sure not to wash the capsules down when I swallow them, to make sure I get to taste it when they split open in my throat, plus that lovely burn they give when they do.

Chloroform doesn't taste half bad either though, and neither does ether. I actually make a special signature cocktail, something I call a 'manhattan project', its 500mg from a bottle of care+ codeine linctus, which uses CHCl3 as a flavouring or preservative or both, poured into the bottom of a glass, then carefully, so as not to disturb it, a mixture of tesco own brand cheap lime soda, not the shitty sugar-free sort though, with fresh lime juice squeezed into it, and some good vodka, poured over the cough linctus to layer one over the other, then using a couple of lime wedges and a lemon wedge, a 'lock gate' is constructed on the top of the glass to hold a little shot glass with a mixture of lime vodka enough to bulk up some diethyl ether, and a grating of fresh lime zest floated on the ether.

Its hard to find the syrup now though, I think I'm going to have to order it online. Makes a mean cocktail though.

Not much of a drinker (prefer ether over EtOH any day) but that particular recipe I've taken quite the shine to. The chloroform works really well with the lime and the ether. Quite surprising to find that of all things as an ingredient in an OTC cough mixture in this day and age. Still, gives it a nice sweet aromatic flavour.

 

[bindingaffinity]

Chloroform doesn't taste half bad either though, and neither does ether. I actually make a special signature cocktail, something I call a 'manhattan project', its 500mg from a bottle of care+ codeine linctus, which uses CHCl3 as a flavouring or preservative or both, poured into the bottom of a glass, then carefully, so as not to disturb it, a mixture of tesco own brand cheap lime soda, not the shitty sugar-free sort though, with fresh lime juice squeezed into it, and some good vodka, poured over the cough linctus to layer one over the other, then using a couple of lime wedges and a lemon wedge, a 'lock gate' is constructed on the top of the glass to hold a little shot glass with a mixture of lime vodka enough to bulk up some diethyl ether, and a grating of fresh lime zest floated on the ether.

Its hard to find the syrup now though, I think I'm going to have to order it online. Makes a mean cocktail though.

Not much of a drinker (prefer ether over EtOH any day) but that particular recipe I've taken quite the shine to. The chloroform works really well with the lime and the ether. Quite surprising to find that of all things as an ingredient in an OTC cough mixture in this day and age. Still, gives it a nice sweet aromatic flavour.

Please write a book of cocktail recipes, because this sounds fantastic.

 

[Pomzazed]

Gib me cocktail recipes too!

 

[Limpet_Chicken]

Well I'd have to experiment more to get enough material for an entire book. That one is more of an LC special. DIPE can be used in place of or with diethyl ether if its all thats to be had (iPrOiPr) (peroxidation hazard, careful, although you probably knew that). With that specific brand of linctus, there actually seems to be enough chloroform in it to need the vodka, otherwise it oils out as blobs on the bottom of the glass. Wouldn't suggest drinking too many of those things though, it does pack rather a hefty kick to it. Not sure if the CHCl3 actually provides any psychotropic effect, but it does really make the flavour of the 'manhattan project'

Although it makes me wonder what I could do with fly agaric, that has a lovely honeyed, but weirdly meaty sort of flavor and scent when its cured.

I've often wondered what could be done with that licorice-ey, treacle-ey spicy flavor of Gee's linctus too. Perhaps something with raki, or ouzo, or pernod. I have made good candy from Gee's linctus before, boiling it down and turning it into a kind of chewy spiced toffee, that was pretty good.

 

[clubcard]

Raw opium in ouzo makes the best laudanum.

 

[Limpet_Chicken]

I'll bear that in mind for this year's crop. I figured there had to be SOMETHING that makes it taste other than like shit. Something like ouzo, raki, absinthe maybe (now that'd give it a kick alright). Or perhaps given the rather low doses needed for a concentrated laudanum simply using 70-80% EtOH, since after a shot of that stuff you can't even taste much of a burn from the alcohol (analgesic doses were given in drops, in some old medical books dating back from the 1700s, that I have in my library [well, strictly speaking, they are currently actually with my GP, the one out of them who's a decent guy, as I lent them to him to read, as I thought he'd get some interest out of reading up on the way medicine was practiced back then, while they were still treating teething pains with mercury metal bashed up into a finely divided mass with chalk, still using lead as an astringent, arsenic as a tonic, HNO3 for treating piles [no joke, thats the treatment recommended, bathing them in nitric acid) and using aq. HCN as a calminative of sorts such as for treating irritable stomachs and overexcitability type conditions, still referencing the difference between the pharmaceutical standard and the stronger acid of Scheele]

Pretty sure there are a couple of recipes for laudanum as it used to be made, although making it taste better wouldn't be a bad thing. (especially since I tend to harvest my crops before they are dried, I don't bother scoring them, just hack them down with a fair bit of straw and throw it in a blender with a pinch of citric acid or two and turn the stuff to a slurry for vac filtration and extraction, if they were fully dried they probably wouldn't grind up too well, and when green both taste and odor are waaay beyond disgusting. Makes me think of isocyanides, not because they smell alike, but because its just...uniquely horrid, gutwrenching with nothing else that you can compare either to, akin to how the only thing you can compare an isocyanide to if you want to describe it to somebody who hasn't smelled one, its pointless because the only thing it can be compared to is another isocyanide. Similar to poppies, it smells like poppy latex and it has a uniquely disgusting stench)

You really should try that toffee recipe though. As much Gee's linctus as you can get hold of, and slowly simmer it and after reducing down the volume, and its still hot and mobile, pour into molds to make bars or bite-sized chunks, or pour onto grease-paper and after it flattens, twist it up into rolls, its delicious, chewy, sweet, but has a lovely spicyness to it and of course, best of all, full of opium tincture. Just remember how much evaporates down into how much toffee, because Gee's also contains squill, and Scilla maritima contains cardiac glycosides, although 2-3 bottles isn't going to cause a heart attack or anything like that (not entirely sure that the glycosides wouldn't break down and split off the sugar from the aglycone portion anyhow)

 

[clubcard]

I'm going back >30 years and not being a fan of ethanol (or much else really) I choked down 75mL. It gave me some insights into the Victorian era, I can tell you. The aniseed taste offset the ethanol (good) but they one is consuming 2 CNS depressants at the same time (bad). With the medications I have to take these days, mixing in other things would not be good.

 

[markosheehan]

Eglumegad seems better than mglu 5 antagonists.

mglu 5 antagonists can cause problems with sleep recovery and overall insomnia I think.

Eglumegad does not do this and it is a 2/3 mglu agonist .

It also seems to cause less amnesia problems relative to MPEP.

has anyone any experience with this? maybe from clinical trials

 

[Limpet_Chicken]

They sure as shit didn't bugger about in those days. Although for sure, some of their methods were rather...questionable...

Heavy metals all over the place, nitric acid up the arse, aconite, hemlock, white phosphorus, Veratrum..its a wonder anybody back then ever visited a doctor. At least, more than once.