I Like to Draw Pictures of Random Molecules

[Limpet_Chicken]

Dotchem-reminds me of a phenylated pethidine, with the nitrogen replaced with an ether bridge.

Not surprising that there is potential for both opioid effects and DARI properties.

That said...what is the potential for it's acting as a convulsant, as norpethidine can?

Another mixed DARI/MOR agonist that comes to mind, is etonitazene, and presumably the other benzimidazole opioids. Although etonitazine is a bit of a hot one to handle, from everything I've read of it. Apparently it surfaced at one point in russia, and was dosed by smoking, a cotton thread being soaked in a solution, and this poked into a cigarette with a needle (and presumably it'd be just as practical to roll your own, with the thread in place). For such a potent sonofabitch of an opioid, not a bad idea, as ideas concerning such potent opioids go to begin with, the slow administration in a cigarette allowing fine control over dosage.

Although the Highsmith case, using via nasal spray, that turned out pretty ugly.

Some of the lower potency benzimidazoles would be safer. Although don't they all have a really short duration of action?

 

[DotChem]

^more like ketobimedone than pethidine.. nor-ketobemidone is not convulsant like norpethidine iirc. the consulvant effect of norpethidine is due to one its metabolites 4-phenyl-piperidine-4-carboxylic acid (GABA-ergic as you might expect!).
re: Etonitazene make sure you don't put a 4-Nitro or any electron-withdrawing on the benzimidazole. It increase MOR by 1000x with very narrow TI the most lethal OP imho.. just don't put a nitro, or a fluoro that sort of things!

@Pomazed:"That is an interesting heterocycle, can that ketone be replaced by an ester?".. why not? but one of the problem with amino esters is their potential to get metabolized to amino acids (CO2Et hydrolyzed to COO2H) by esterases. They tend to give GABA-ergic ligands that are sometime convulsants especially those with piperidine (cf ketobemidone v meperidine).. but who knows with this particular structure?

@Gaffy: "

I Wonder if it'll compare to CarFentanyl potency wise" the N-substituted derivative with phenethyl is about 300xmorph or ~ 3X less than carfentanyl. The cis. the trans is inactive at OP but is a SNDRI. But why would anybody want to do that (increase potency to carfentanyl range!). Besides just being lethal killing people (I mean fentanyl OPs) they're not even euphoric..A lots of people I know hate them. Maybe put a N-methyl, may not be as potent as fentanyl but most likely more morphine like opiates

Ketobemidone type are probably one of the most overlooked RCs class yet.. The perfect speed-ball with simultaneous DARI + MOR within same dosage (not insanely potent and lethal like fent-type OP)​

​

 

[Soulfake]

N-Methylated Phenidates are less potent than the usual ones, around 1/10th the potency.

I thought for example the para-fluoro substitution of 4F-MPH or the naphtalene of HDMP28 could compensate for the loss of potency on the Morphenates and the n-methylated Phenidates and result in a still potent enough substance. Also Methylnaphthidate is very strong but short acting, Isopropylphenidate is smooth and long acting so Isopropyl-Naphthidate could be a good fusion of those.

---

some more molecules

Some "speedball-esters" and a giant cyclic opioid...if it just could be that easy, haha

 

[Gaffy]

Anyway; Read DotChem's thread about "Eagle Night", a new "drug" that can keep one awake for 4 night's with no comedown, and that is supposedly non-dopaminergic and not a racetam; that seems quite hard to me. Anyway I looked into non-AMP stims and came up with two little ones, a quinoline and a bromantane derivative; image also includes a novel stim (not of my invention), w/ link to the paper:

 

[Gaffy]

Came up with something, I'll edit post when I'll access a computer.
Edit:

I haven't a program to simulate binding profiles but I presume these to be non-PEA DAT NET SERT (s).
Didn't yet look at MT antagonists so the ones I drew higher-up might be more agonists at non-MT sights;

Might just be getting closer to "the Night-Eagle".​

 

[Soulfake]

Some more simple molecules. If nicotinoyl-GABA has a better transportation across the BBB maybe that would also work with Phenibut or Gabapentin which are known to be only transported into the brain in small quantities. I wonder if nicotinoyl-GHB would be possible (the one below the first structure). Nicotinoyl-Amphetamine/Cathinone/etc. analogues could be nice as the niacine would help against the vasoconstriction and in some countries such analogues would be legal.

 

[Gaffy]

Enough Night Eagle, back to ketobemidone:

 

[sekio]

thiophene is probably a better substitute than benzothiophene...

2- and 3- position isomers of "thiophenyl-ketobemidone".

makes me think of thiambutenes

 

[Gaffy]

Maybe. But TCP is a NMDA antagonist "TCP has slightly different binding properties to PCP, with more affinity for the ​

NMDA receptors[FONT=Verdana,Arial,Tahoma,Calibri,Geneva,sans-serif]"[/FONT]

unlike BTCP "benocyclidine is a pure DRI with negligible ​

affinity

for the ​

NMDA receptor

"; full DRI. Kinda what I aimed for, as we were speaking of speedballs; DRI(DA)/MOR, Nothing else.
Btw your thiophene ring is misplaced (I think).​

 

[Limpet_Chicken]

Cathinones have a carbonyl group in the beta-position, not a hydroxyl group. No ester there, sorry.

There are ways of protecting them though, from that nasty habit of dimerization. Pthalimidopropiophenone, IIRC was sold in israel for a while, it certainly has been used, in humans, that is. Oral administration being mandatory, however, as it's dependent on cleavage to the cathinone and pththalic acid in the acidic conditions of the stomach.

A carbamate could likely be done too, again, oral use. This could be...tweaked, so to speak, pun intended, so as to smooth the comeup, if one were to form the carbamate of an alcohol with a real kick to it.

I've long wanted to get round to preparing and testing the 1-ethynyl-cyclohexan-1-ol carbamate of MDA. Probably relatively small amounts of the alcohol in question released, but it IS known to be a potent little sucker, or maybe an ethchlorvynol carbamate of MDA. Aside from R&D to be done, something novel to explore, the benefit being, ideally, one hopes, a smoothened come-up and ride, the rough edges filed off, not full blown intoxication, just, sanding down the jittery bits for something just that bit nicer.

That at least, is the hope.

As for speedballs, actually some NMDA antagonism in with such a beast, or even a combination of NMDA antagonist+potent opioid, it can really make a difference.

Something like memantine+dipropionylmorphine, 6-AcO-dihydromorphine, or even morphine if one either cannot, or doesn't wish to get out the chemistry set, so to speak.

The two in the same rig, speedball-fashion...the rush is massively prolonged. And potentiation through the roof.

Memantine+prope gear in the same rig..it'll knock you on your ass so hard you'll think Thor himself just wrapped his bedclothes round Mjolnir and went to town on you. I've combined the two also with 6-AcO-dihydromorphine, and despite having at the time, an opioid tolerance larger than I do now, 300mg of the opioid, 100mg memantine, IV, I was staggering around the house for the best part of an hour, at least 3/4 hour, before the IV rush subsided (to an extent) and the high began.

And at the time, I'd still be breathing after 1g-1.5g morphine IV, dissolved in water as hot as tolerable without discomfort or injury, and using a large capacity glass syringe. Hell, had done 1g shots of DPM before, with the bastard of a tolerance I had at the time, and that 300mg 6-AcO-DHM (there'll have been a smaller proportion of dihydroheroin in it, from the route that was responsible for it's creation), with the memantine, fuck ME. Quite literally, staggering, as if I'd chugged a 70cl bottle of vodka and added benzos to it (I'm not much of a drinker, and no, I'm not suggesting I either DO this, or suggest anyone else do it either, it's the comparison that is salient)

Having to hold on to sofas, chairs, tables, had to go down the stairs with great care, partly on my arse, literally. The potentiating effect of NMDA antagonists on opioids, when co-administered, certainly with memantine, it's absolute rocket fuel.

Never tried mixing the two with a stimulant for a three-way NMDA antagonist-speedball.

But I wouldn't say no to a couple hundred mg memantine, 300-400mg 6-AcO-DHM and a decent serving of 3-fluorophenmetrazine
Had opioids+3-FPM, opioids+memantine, but never opioid/stimulant/NMDA antagonist.

Unless you count diphenidine, but I don't mean 'mostly one with bits of the other two', but in all three cases, something that'll really pull it's weight.

Memantine might not be much of a dissociative unless dosed really high, but it DOES potentiate opiates to a staggering degree.

 

[Soulfake]

Sorry for the stupid question but I'm just on stimulants and always like to draw random molecules while I'm on stims ^ ^

I have often read that the nitrogen in Amphetamines, Cathinones and similar drugs isn't always necessary to retain activity, what would putting a methylsulfonylmethane-unit instead of the amine or one at the para-phenyl position do to the molecule? I guess it doesn't really make sense because it's too bulky, reactive or something like that but I have often seen those msm-units in various drugs and find them somehow interesting.

 

[Pomzazed]

Sulfone is not that much reactive.
I have no idea about paramethylsulfonyl, but for the other one it should lost activity as that amine nitrogen is in protonated (ammonium) form during binding

 

[Gaffy]

Missed the 666,666 views, got 666,696

Yay:

 

[Hodor]

Sorry for the stupid question but I'm just on stimulants and always like to draw random molecules while I'm on stims ^ ^

I have often read that the nitrogen in Amphetamines, Cathinones and similar drugs isn't always necessary to retain activity, what would putting a methylsulfonylmethane-unit instead of the amine or one at the para-phenyl position do to the molecule? I guess it doesn't really make sense because it's too bulky, reactive or something like that but I have often seen those msm-units in various drugs and find them somehow interesting.

Sumatriptan is essentially 5-(N-methyl-sulfoneamido)methyl analogue of DMT. This limits its activity as a serotonin agonist to mostly the 5HT1x receptor subtypes, some of which are apparently responsible for causing vasoconstriction in the brain, thus stopping migraines and cluster headaches.
Seeing as how meta- and para-substituted amphetamines are also associated with serotonin receptor agonism, one wonders if sticking a bulky-ass methylsulfonyl group there would achieve similar effects. .. it's a long shot, though. IIRC tryptamines generally have some degree of 5HT1x agonism to begin with, whereas phenylethylamines are more selective for 5HT2a/b/c.

I kind of doubt you can replace an amine with a sulfone group, at least not without a massive drop in potency. I believe sulfonyls can sometimes act as bioisosteres for carbonyl (i.e. C=O) groups, though.

 

[S.J.B.]

I have often read that the nitrogen in Amphetamines, Cathinones and similar drugs isn't always necessary to retain activity...

If that is the case, it is exceedingly rare and not, to my approximation, anything that has ever shown up in a recreational drug or approved CNS medicine.

 

[Pomzazed]

In phenethylamine class, nitrogen seems mandatory.
What is not-that-require is in the structure of cocaine and phenidate types, that N can be replaced by O or CH2 with drop in potency but not fully lost.

 

[white55]

some unstandard benzo subs, do you think they would be active/commercially viable to make?

tfm at r7, active?

nitemazepam analog, do you believe the potency would be high enough to be useful?

nimetazepam with a bioisostere for the nitro group? active?

 

[sekio]

some unstandard benzo subs, do you think they would be active/commercially viable to make?

fluorosulfonyl groups are too reactive to be good subtsituents on drugs

 

[Pomzazed]

That SO2F looks like you’re making an insecticide o.o

 

[Limpet_Chicken]

Yeah, I'd rather not eat that one.

Nitrotemazepam..not an untempting thought. Nitrobenzodiazepines are where it's at, IMO, as far as benzos go. Temazepam is or has been REALLY popular recreationally in the UK, to the point where they had to ban the 'jelly egg' form of it, because addicts were heating it to melt the stuff and banging it, often causing horrendous damage to vasculature and tissue damage, limb loss etc. Only ever got to have two bottles of jelly egg temazepam, after finding an old lady's stolen handbag as a young kid, returning the bag to her, her money had been stolen, but her cards and stuff still there, so I returned it all to her, but she said she wasn't gonna take those pills, after the label had gotten wet, near the brook the bag was thrown beside, gave me 20 quid for returning the bag to her with her cards, asked her if I could keep the two bottles of temazepam jellies in there, because they were getting rare as shit even then. She said yeah, go ahead, don't know why you'd want those but sure if you want them, keep them'

That was a fun week or so, shoveling down those, chomping on 'em like jelly beans (no, I didn't think they were candy, just used them like they were chewy jellybeans)

Apparently, not sure if it still is, but temazepam was at least at some point classified differently, class B compared to other benzos I think, or it might have been a different schedule, one step above the other benzos due to recreational popularity. Pretty fucking stupid IMO, since they'll most of them get one fucked up, if one has enough, and just as, or more, addictive physically. A 1,4-benzo is a 1,4-benzo as long as they are both of the GABAa PAM kind. Horses for courses.

Personally I've never seen why it might be special, I've had it enough, but it's kinda bland to my tastes. Needs a nitro group sticking on it

Had plenty, especially after several years back, kicking the fucking little psycho borderline waste-of-autism BITCH from hell housemate I ended up having for a while into the street, after she tried to run me through with her samurai sword. Went through all her stuff before returning any of the bits I didn't decide to take for my own. And among the shit I did (she was a real klepto nutball gorgonslut bitch from Hades), was a LOT of temazepam and valium scripts. Loads of 'em, had the scripts, rarely used them. So naturally I relieved her of them.

She was a wanker. But, a wanker from perdition with a lot of valium, temazepam, plus DFs she'd siphoned off from me over years, just to manipulate me with fucking meptazinol and BZDs, when I'd go into WD, couldn't take them herself, had to use meptid for her own pain because she was allergic to hydrocodone, and severely so, so likely so to codeine and DHC. Ugh, total bitch. Although at least when kicked out, got myself one hell of a party-plate