N&PD Moderators: Skorpio
dissociatives of the future
Jamshyd
Bluelight Crew
^ In that case, I would agree with you
Although the word "affinity" is technically incorrect in this context, I believe. That is why I got confused.
fastandbulbous
Bluelight Crew
toxide said:
The duration of action has nothingto do with affinities, but is related to the ease of excretion (which is related to how polar it is). The keto group on the cyclohexyl ring makes it a lot more polar than PCP, so it (and it's metabolite norketamine) gets excreted more quickly. PCP is notorious in toxicology papers for being reabsorbed into the bloodstream from the bladder due to it's lipid solubility.
2-phenyl-2-(N-ethylamino)cyclohexanone is the ketamine version of PCE, not PCP. It's also not that difficult to synth if you start with phenyl cyclopentyl ketone. The 'ketamine equivalent' of PCP is 2-phenyl-2-(1-piperidyl)cyclohexanone - regardless of the substituents on the tertiary amine (piperidyl for PCP, methylamino for ketamine), the defining difference between PCP like compounds and those like ketamine is the keto group on the cyclohexane ring. It's a big polar handle on the molecule that allows for fairly rapid excretion compared with the plain cyclohexane derived compounds like phencyclidine (PCP). The reason PCP that's been excreted unmetabolized gets back into the bloodstream is that it's a quite non-polar, lipid soluble molecule under physiological conditions, so it just diffuses across the bladder wall back into the blood - that's why the after effects of PCP last so long (like a day or two). Ketamine, on the other hand has this big polar oxygen atom stuck on the cyclohexane ring. It makes for easier metabolism and reduces lipid solubility by a fair amount, so it can't sneak off back into the blood after being concentrated in the bladder for removal. Turns the 4 hours of PCP & related drugs into the 45 mins/1 hour of ketamine, tiletamine etc. The 2-chloro group is there to improve it's analgesic activity - a good trade off against potency for a useful clinical drug; a 3-methoxy group does a similar job by increasing affinity for the mu opiate receptor.
Actually, there's a drop to half the potency of the cyclohexanone ring compounds (like ketamine) when it's replaced by an hydroxy group (cyclohexanol ring), but I'd bet it's in & out a bit (or possibly even a lot) faster than ketamine & company :D . The hydroxy group is even more polar than the keto version meaning that the fuzzy after effects would be even shorter. Mind you, ketamine isn't exactly a small dose compound (80-100mgs for the full whack!), so the ring hydroxy derivative of ketamine (2-(2-chlorophenyl)-2-(N-methylamino)cyclohexanol) would probably require double or even a bit more times the dose of ketamine to get the full show. 160-200mg is an awful lot of drug to be putting into a muscle, I pitty the poor bastards that have to snort a fuck-off sized line of nasty, irritating white powder 
. You'd be snorting 1/4 gram lines to get to a k-hole like state without any tolerance. With the way tolerance seems to escalate with NMDA antagonists, before long you'd have to be like a vacuum cleaner to hoover up a full dose - and most likely it'll be just as irritating to the mucous membranes (the few times I've tried snorting it, ketamine leaves me with red raw nostrils - and occasional bit of blood 
). I'm cringing at that very thought at the moment
Last edited:
ebola?
Bluelight Crew
>>I pitty the poor bastards that have to snort a fuck-off sized line of nasty, irritating white powder . You'd be snorting 1/4 gram lines to get to a k-hole like state without any tolerance.>>
Odd. I found ketamine to cause little irritation and no pain. Just mild itching. But, yes, I'd consider a quarter gram to be an unmanageable quantity.
ebola
perhaps changing ketamine hcl to a different salt. Ketachloride I used to thing was a totally different chem from or a k analog cuz the eefects were different, i've done some chloride recently which happen to be on of the most pleasant powders i've put up my nose. it was crystally and tasted almost salty at first which made me think it was cut but it mosdef wasnt. I sniffed the whole gram over 1/2 hour, I had to declog my nose once, but other than that I really enjoyed sniffing the whole thing, not much drip either, and i usually hate sniffing shit
Jamshyd
Bluelight Crew
I find ketamine gives a very small sting for one second, but that immediately goes away. As for the smell/taste, I prefer to call it "accquired"
ebola? said:
. Yes, it is acrid, but it has become one of the most beautiful sensations for me!
250mg is not too big if you take it gradually over 15mins. It always worked for me, anyway. I enjoy snorting K... IMing has always scared the shit out of me, and I am not always in the mood to IV it.
fastandbulbous
Bluelight Crew
Possibly just me then - I have iffy sinuses (currently taking antibiotic because of infected sinuses) that flare up very easily, which is why I hate snorting drugs of any kind. It's an option that's way down the list as a route of administration for me - I'd rather IM or administer rectally a drug before snorting (as long as aseptic technique is followed for preparation etc of the IM dose). The only common route that I consider below snorting is IV administration, mostly because the sight of a needle entering flesh really does a number on me (you can IM without having to watch the needkle go in, not so for IV).
Actually, for that I am somewhat grateful as if I could stand the idea of IVing drugs, I'd probably have really gotten into deep water with some drugs. From the problems I've had over compulsive IM doses of ket in the past (pretty much got that in hand now), me and IV drugs would just be a disaster waiting to happen.
I'll leave poking holes in veins purely in the hands of doctors...
kidamnesiac
Bluelighter
what about making the ketone a terminal alkene, ala the similar idea F&B had for the PEA 5-HT ligands?
long lasting with similar electronic properties?
^not seeing the IM is a huge difference. I don't think I could IV and snorting also sucks imo. I like my sense of smell and dislike pain. Nothing wrong with nurses (well-endowed ones if I could request) poking holes in my veins though
fastandbulbous
Bluelight Crew
Nah, one of the joys of ketamine is it's short acting nature, using an alkene to replace the keto reduces it's polarity considerably and would most probably make it reabsorbable from the bladder in the same way PCP is. You actually want a polar group on the molecule to facilitate excretion
hussness
Bluelighter
Yeah, this seems to be one of the fundamental enigmas of drug design.
MattPsy said:
parke davis have already been there, in the late 1960's and early 1970's to be precise, where they identified a family of ketamine analogs with increased potency and reduced duration compared to ketamine. Though for medical applications ketamine duration is about right, which is probably why they didn't run with them.
hussness
Bluelighter
^Were these results published?
hussness said:
yes and no, they are mentioned in a couple of patents without the supporting data. and I have a couple of papers somewhere that discuss them. They are derivatives of Nor 2-phenyl-2-amino cyclohexanone substituted on the nitrogen.
I am shpongled
Bluelighter
I'd really like to see a more potent version of salvorin-A someday. It's too hard to smoke in its current form (but it does work.)
kidamnesiac
Bluelighter
what about swapping the ketone for an imine?
kidamnesiac
Bluelighter
but how metabolizable would that acetyl group be? it's in a funky (sterically hindered, don't you know thats what funky means?) spot and may not come off easily...the advantage of the ketone or other species as such is the tautomerism, yes?
