(+)-Ketamine - another MDA?

[fastandbulbous]

And by that I mean is it looks like a case of one isomer being substantially different from the other in terms of effects. With MDA, the bulk of the entactogenic activity resides in the S isomer and the psychedelic activity in the R isomer, giving 3 distinct experiences from the racaemate and two pure isomers. With most drugs, it's just a simple case of one isomer being more active, but essentially the same. With ketamine the S (+) - isomer is markedly different from the racaemate, which makes me wonder what the (-)-isomer would be like.

Working by a sort of process of deduction (comparing racaemic ketamine with the S-isomer), it looks like almost all the opiate-like and anaesthetic activity resides in the R-isomer (would have to check, but it looks like the R-isomer might have the same absolute conformation as the more potent isomer of opiates). While this def wouldn't appeal to the people using ketamine for psychotherapy, it may have a useful role in pain management etc and would seem to be quite an appealing drug of abuse for some.

Does anybody have any info etc on the psychopharmacology of the pure R-isomer?

 

[kidamnesiac]

So, your deduction tells us what the not-experienced is like, what is the S isomer up to?

WRT MDA: Which isomer is it that is responsible for the repeated full body orgasms?

 

[fastandbulbous]

Yeah, the racaemic compund is like a joint effort between two distinct identities combined to give the total effect- bit like a unique drug combination. The S-isomer has all the divergent analytical thought trains going on, which is one distinct part of ketamine for me, but none of the warm blanket, opiate feel of the racaemate.

Maybe the pure NMDA antagonist-like effect can be teasted apart from the anaethesitized, opiate like state that produces the alternate dimension quality which is an equally distinct feature of the racaemate experience.

When you consider that dextromethorphan has dissociative properties, but levomethorphan is a dihydrocodeine like opiate (although a shitload of other receptors get tweaked at the same time with DXM), it doesn't seem such a strange idea that the two isomers of ketamine might be radically different.


Full body orgasms with MDA - where in the instruction manual* does it mention such things with MDA?

* - Homo sapiens, the buffoon's guide to!

 

[kidamnesiac]

call me crazy or neuronally challenged, but MDA is the most physically euphoric thing i've ever experienced, even at <80mg. MDMA does next to nothing for me besides a hangover, even up to almost 200mg. I guess it makes most music sound bad...My significant other is the same way-her reaction to MDA is SEX SEX SEX while the methylated is benign. I am sure of the purity of the material.
Ok, not going to hijack the thread-
I will try to find a few scholarly articles on the receptor profiles tonight

 

[Jabberwocky]

Wait, you're saying the S isomer of Ketamine retains all of the psychedelic effects without the opiate pain killing? That sounds WONDERFUL! Would this make for a more clear headed K-hole (kinda oxymoronic?)?

I believe the S isomer was available...

 

[Junglistvibe]

I recently ran into ketamine which has a different high than what I'm used to. I was going to start a thread about it because it intrigues me. What I know for sure is that it's most likely pure(crystals) and it's cheap. What I don't know for sure is if it's the +-isomer or it's because of me not having done K for a while or it's because it's something completely different. It could well be the isomer seeing as my friend always has a good source for rather rare drugs(MDA crystal, RC's, PCP, 5-MeO-DiPT massage oil, cheap MDMA or amphetamine)...

Description of the high: physically it's a lot less intense. I know with normal K I can sit there and just enjoy how I feel, completely fucked up and thinking about complete random things. That's not the case here. My thoughts are different, much less gibberish and more focused. I think it's almost possible to have a bad trip with this stuff. I've had a few cases of paranoia but that's most likely because I do it in my parents house.
I had extremely intense aural hallucinations yesterday. I could've sworn somebody was playing heavy beatdown guitar riffs for over 3 minutes in the room next to me while in fact, I was listening to a fan.
Visually it's the first time I noticed tracers on ketamine. My pupils/facial expressions still look relatively normal. There is motor impairment but I can't say if there's less of it or not. I can actually play computer games to some extent

This is the first time my friend was able to K-hole with ket. I haven't tried a K-hole dose yet, I'm kind of scared because it doesn't have this familiar feeling to it

 

[AcidRain]

Was that that really gritty stuff that looks a bit like sand in terms of shape of crystals?

I had it once and it felt horrible :/
(as opposed to the normally kind of flaky dandruff looking k)

 

[Junglistvibe]

Do you think you can tell what ketamine it is by the looks of it?

It's always in crystal form here. But this time the crystals are bigger, and long/needle-shaped.

 

[AcidRain]

I remember there was a thread about some kind of grainy k a while ago, cant find it though. people seemed to agree that it felt shite from memory.

The long needley crystals is what i meant by flaky dandruffy stuff I think. .

I cant say if its a particular isomer or anything but it felt so much nicer than the grainy gunk. IMO of course.

 

[hussness]

Here's a patent on separation of the isomers:
http://www.freepatentsonline.com/6040479.html

 

[kidamnesiac]

Differential effects of ketamine enantiomers on NMDA receptor currents in cultured neurons


Abs:
The effects of R- and S-ketamine on N-methyl-D-aspartate receptor-activated cation currents (NMDA receptor currents) of voltage-clamped cultured rat hippocampal neurons were investigated using the whole-cell patch-clamp technique. Both enantiomers exhibited a voltage- and use-dependent blockade of NMDA receptor currents, with the S-enantiomer being about twice as potent as the R-enantiomer. Calculated relative forward and backward rates suggest that conformational differences influence the dissociation from the binding site more than the association with it.

I can't get this one (no med school )

White PF, Ham J, Way WL, Trevor AJ: Pharmacology of ketamine isomers in surgical patients. Anesthesiology 1980; 52:231-9.
But I'd like to (wink wink)

The Effects of Ketamine and Its Enantiomers on the Morphine- or Dexmedetomidine-induced Antinociception after Intrathecal Administration in Rats.

Conclusions: These data indicate that racemic ketamine and S (+)-ketamine, but not R (-)-ketamine, exhibit similar effectiveness in potentiating the antinociceptive effects of both morphine and dexmedetomidine.


Ketamine: Teaching an Old Drug New Tricks

S(+) ketamine binds approximately two- to fourfold stron-
ger to TV and K-receptors than does R(-). Still, the
affinity of ketamine for these receptors is 10 (p) to 20
times less than for the NMDA channel, which
(K) suggests that the interaction is not of major clinical
importance. This is confirmed by findings that nalox-
one does not reverse the analgesic effect of ketamine
in humans (30).

R(-) ketamine inhibits the neuronal uptake of nor-
epinephrine, and S( +) ketamine additionally inhibits
extraneural uptake, thus inducing a prolonged synap-
tic response and increased transfer of norepinephrine
into the systemic circulation (34). The uptake of dopa-
mine and 5-HT is inhibited similarly (38), which could
lead to an increase in central dopaminergic activity.
The 5-HT antagonist methysergide antagonizes the
analgesic effects of intrathecal ketamine, implicating
serotonergic mechanisms in ketamine analgesia (39).

Convincing evidence for a lower inci-
dence of psychotomimetic side effects after S(+) ket-
amine administration could not be documented.
Nonetheless, the patients felt more comfortable after
S( +) ketamine (49), and a larger proportion of patients
would be willing to have a repeat anesthetic with
S( +)compared with the racemic mixture (85”/0vs 65%),
mainly because of decreased agitation, disorientation,
and anxiety (19).

bug me for pdf

not sure whether to call you a liar, high, or ugly

 

[vecktor]

some thoughts
ketamine is a sub optimal ligand for the NMDA channel site, (the PCP1 or high affinity PCP site,) so I would expect both enatiomers have non competitive NMDA antagonist properties. The peripheral NMDA receptors are subtly different to the brain ones so it might be more or less selective in where it acts. if ketamne had higher affinity, then the two antipodes might have more marked differences in NMDA antagonist activity.
the opiate type action of ketamine seems to reside in the s enatiomer, as does some of its dopaminergic and other activities, I forget which particular ones.
I have never tasted the two enatiomers separately, those that have tasted the s reported it to be not as good as the racemate for insight and power and usefulness. I suppose as the s enantiomer becomes more widespread, i think it is still on patent at the moment and so the generic and chinese stuff is mostly raceamic, then the taste and effects of K might change subtly. I do not know of anyone who has tasted the pure R enantiomer. who knows the R enatiomer might be the one that causes the delayed antidepressant effects?

I don't believe that the two enatiomers form visably different shaped crystals except when they are diasteromic salts ie salts with a chiral acid, such as tartaric acid, and as most ket is hydrochloride the two enantiomers or the racemate would most likely look identical. on the whole the different shapes and sizes are due to speed of crystalisation/ evaporation or the prscence of trace impurities which prevent proper crystaisation, some of the vials contain stabilisers and antioxidants and antibacterials which do effect crystalisation.

V

 

[Jabberwocky]

^^^ Are you sure about that? Its pretty much opposite of what FB said.

The S-isomer has all the divergent analytical thought trains going on, which is one distinct part of ketamine for me, but none of the warm blanket, opiate feel of the racemate

the opiate type action of ketamine seems to reside in the s enatiomer,

I'm confused, then again I'm a little slow on the uptake.

Also, Fastandbulbous...I'm extremely interested in the following comment but can't quite understand it:

Maybe the pure NMDA antagonist-like effect can be teasted apart from the anaethesitized, opiate like state that produces the alternate dimension quality which is an equally distinct feature of the racaemate experience.

But, vecktor seems to be saying that they are both equally NMDA antagonists, no?

Sorry, I'm dumb when it comes to this stuff! 8)

 

[fastandbulbous]

I was just thinking out load, comparing the states produced by each - that's why I posted the thread to see if anybody out there had any extra info

 

[B9]

Subjective opinion of subadvanced drug disussion lurker.


S+ isomer ket is waay nicer than racemic etc, why or how I dunno, the magic of chemistry is a contender though.


Ah I feel better now, contribution is good (even when it is valueless )


Have fun now!:D

 

[vecktor]

Subjective opinion of subadvanced drug disussion lurker.


S+ isomer ket is waay nicer than racemic etc, why or how I dunno, the magic of chemistry is a contender though.


Ah I feel better now, contribution is good (even when it is valueless )


Have fun now!:D

did you do the same doses? the s is a bit more potent than the racemate.
from memory something like 5 times the affinity and perhaps twice the activity at NMDA.

on a side note the two enatiomers of ketamine are metabolised at different rates to norketamine. the s enantiomer being metabolised faster to norketamine I believe has activity at the concentrations achieved after taking ketamine especially with oral doses which would be more extensively metabolised.

 

[kidamnesiac]

Both enantiomers exhibited a voltage- and use-dependent blockade of NMDA receptor currents, with the S-enantiomer being about twice as potent as the R-enantiomer.

the "Teaching an old drug new tricks" paper has the clinical dosage comparisons between the S and R

 

[B9]

did you do the same doses? the s is a bit more potent than the racemate.
from memory something like 5 times the affinity and perhaps twice the activity at NMDA.

on a side note the two enatiomers of ketamine are metabolised at different rates to norketamine. the s enantiomer being metabolised faster to norketamine I believe has activity at the concentrations achieved after taking ketamine especially with oral doses which would be more extensively metabolised.

Ah basically my experience is that it is cleaner , less wooly on the mind, lasts a fraction less time at the optimum part of the experience, and after a few trials I am sure it is a little stronger, but not a great deal stronger.

Definitely better though, and that's what every other forum wants to know, just you crazy people thinking " Now this feels GREAT , I wonder why , it's gotta be some reason" etc

But I love yous anyway :D


[edit zophen] Ah sorry didn't mean to be speciesist Vecktor, I meant crazy people and crazy AI lifeforms, no matter what they're powered by.

 

[haribo1]

Just how difficult is it to seperate the two isomer? Is it a simple case of salting with an optically active acid? If so, assuming the + isomer is so much better then maybe it's twice as valuable? Removing that Cl & swaping the N-methyl for an N-ethyl should make a product four times stronger & then seperating the isomers might produce a *WOW* product...

 

[hussness]

Check my patent link above...