Difference in effects,side effects , addictions of pseudo vs ketone ice.

[Sameria]

^ That's correct. It's unsubstantiated whether L-isomer has any psychoactive effects at all, so it follows that a pseudo preparation with all the meth being D-isomer will be more euphoric than the ketone, which is only 50% D-isomer. Of course this assumed that both prepartions are pure, but since all meth is cut, it's not guaranteed which preparation will actually contain more D-isomer. The crystallisation process for ketone is actually quite tricky, so you're actually almost guarauteed to get 50% D-isomer in those shards, whereas straight d-isomer shards can be cut much more easily with msm and others.

...Hope that made sense.

Excellent insight. Thank you kindly

 

[headdah]

just picked up some ice here in a-town.

I believe it is also Keytone.

looks exactly like any other ice i've gotten be4, but theres a slight weird taste to it.
Initial rush is the same. but has no legs to it. It almost feels like within 30mins of puffing, you are back to baseline.

 

[Mr Blonde]

^ Getting ice that is a racemic shouldn't affect the duration, just the effects slightly. Both isomers are long-acting and the d-meth content should still be enough.

 

[pisspotnrock]

thanks for the post footscrazy, very informative

 

[phase_dancer]

L-methamphetamine does not cross the blood-brain-barrier as far as I am aware; even if it does, it must not bind to the same targets that d-methamphetamine does. L-methamphetamine must primarily work as a neurotransmitter releaser in the sympathetic nervous system; the release of these substances being what causes the nasal decongestion and the degree of stimulation is reportedly has.

Why should it not cross the BBB? It is as lipophilic as the dextrorotatory isomer. It undoubtedly binds to some receptors the d isomer binds to, and probably also binds to other targets differently, which results in variation in effect, less potency at lower doses and different peak periods of euphoria. It certainly causes a similar stimulation at higher dosages...more below.

Crystal methamphetamine has to be (well, usually ) only d isomer, as they are symmetrical and can form a lattice. Throw in a different shaped building block (l isomer) and it throws the whole pattern out, so crystals can not be formed.

Many racemic compounds form crystals. What about MDMA crystals? The probable reason why much racemic meth isn't crystallised is due to the half arsed educated cooks. There are several crystalisation techniques that could be applied to racemic meth that I'm sure would work. Studying chemistry, students learn a variety of these techniques, applied to other compounds of course.

There's no surefire way to indentify ketone vs pseudo meth by appearamce.

Yes there is. Viewing the degree of optical rotation using a polarimeter.

The l-isomer does not act centrally; that is, no euphoria or intellectual stimulation. It acts mainly as a stimulant in the sympathetic nervous system and would produce 'jittery' effect.

If you've ever taken selegiline, you'll know that the metabolic products which include L-meth and L-amphetamine, are centrally active. L-meth has a half life similar to D-meth - actually, slightly longer; and while there is a degree of peripheral stimulation, the CNS activity is definitely there, even with lower doses of selegiline. Perhaps it has something to do with where the metabolites are formed i.e. the cleaving of the propargyl moiety

Human pharmacology of the methamphetamine stereoisomers.
Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P 3rd, Everhart ET, Jones RT.

Addiction Pharmacology Research Laboratory, California Pacific Medical Center Research Institute, St Luke's Hospital, San Francisco, CA 94110, USA. [email protected]
Abstract
OBJECTIVE:

To help predict the consequences of precursor regulation, we compared the pharmacokinetics and pharmacodynamics of the methamphetamine (INN, metamfetamine) stereoisomers.
METHODS:

In this study 12 methamphetamine abusers received intravenous d-methamphetamine (0.25 and 0.5 mg/kg), l-methamphetamine (0.25 and 0.5 mg/kg), racemic methamphetamine (0.5 mg/kg), or placebo with the use of a 6-session, double-blind, placebo-controlled, balanced crossover design. Pharmacokinetic measures (including area under the plasma concentration-time curve [AUC], elimination half-life, systemic clearance, apparent volume of distribution during the elimination phase, and apparent bioavailability) and pharmacodynamic measures (including heart rate, blood pressure, respiratory rate, and visual analog scale ratings for "intoxication," "good drug effect," and "drug liking") were obtained.
RESULTS:

Pharmacokinetic parameters for the individual enantiomers given separately were similar, with dose-proportional increases in AUC and maximum plasma concentration. After racemate administration, the AUC for d-methamphetamine was 30% smaller than that for l-methamphetamine (P = .0085). The elimination half-lives were longer for l-methamphetamine (13.3-15.0 hours) than for d-methamphetamine (10.2-10.7 hours) (P < .0001). Compared with placebo, d-methamphetamine (0.25 mg/kg, 0.5 mg/kg, and racemic) increased the heart rate (P < .0001), blood pressure (P < .0001), and respiratory rate (P < .05), and this increase lasted for 6 hours. The peak heart rate changes after racemic methamphetamine and 0.5 mg/kg d- and l-methamphetamine were similar (18.7 +/- 23.4 beats/min, 13.5 +/- 18.5 beats/min, and 10.7 +/- 10.2 beats/min, respectively), but racemic methamphetamine and 0.5 mg/kg d-methamphetamine increased systolic blood pressure more than 0.5 mg/kg l-methamphetamine (33.4 +/- 17.8 beats/min and 34.5 +/- 18.9 beats/min, respectively, versus 19.5 +/- 11.3 beats/min; P < .01). l-Methamphetamine, 0.5 mg/kg, was psychoactive, producing peak intoxication (46.0 +/- 35.3 versus 30.3 +/- 24.9) and drug liking (47.7 +/- 35.1 versus 28.6 +/- 24.8 ) ratings similar to 0.5 mg/kg d-methamphetamine, but the effects of l-methamphetamine dissipated more quickly (approximately 3 hours versus 6 hours). The effects of 0.25 mg/kg l-methamphetamine were similar to those of placebo. Racemic methamphetamine was similar to d-methamphetamine with regard to most pharmacodynamic measures.
CONCLUSION:

The pharmacokinetics of the methamphetamine enantiomers are similar, but there are substantial pharmacodynamic differences between the isomers. At high doses, l-methamphetamine intoxication is similar to that of d-methamphetamine, but the psychodynamic effects are shorter-lived and less desired by abusers. Racemic and d-methamphetamine have similar effects and would be expected to have comparable abuse liabilities.

http://www.ncbi.nlm.nih.gov/pubmed/17015058

colour added for emphasis; p_d

 

[Mr Blonde]

Yes there is. Viewing the degree of optical rotation using a polarimeter.

I suggested that in another thread a couple of weeks ago, ha ha.

Re: selegiline, I didn't know that it was considered that l-methamphetamine and l-amphetamine contributed major effects. All I have though is a PubMed abstract.

A frequent topic of controversy has been whether metabolism of l-deprenyl (selegiline) to active metabolites is a detriment to clinical use. This paper reviews possible roles of the metabolites of l-deprenyl in producing unwanted adverse side effects or in augmenting or mediating its clinically useful actions. Levels of l-amphetamine and l-methamphetamine likely to be reached, even with excessive intake of l-deprenyl, would be unlikely to produce neurotoxicity and there is no preclinical or clinical evidence of abuse liability of l-deprenyl. In contrast, there is evidence that l-amphetamine and l-methamphetamine have some qualitatively different actions than their d-isomer counterparts on EEG and cognitive functioning which might result in beneficial clinical effects and complement beneficial clinical actions of l-deprenyl itself.

In your study, the bold part states that administration of l-amphetamine was less desired by users but they then claim it has similar abuse properties as the dextro isomer? And earlier on they claim that the drug liking was similar as well.

From anyone I've ever talked to in America who has access to the levo isomer OTC, they do not recommend it as a stimulant, even above propylhexedrine. Increased peripheral stimulation compared to euphoria and mental stimulation is one problem that would limit abuse potential, and is why l-methamphetamine is still OTC in the USA.

 

[footscrazy]

phase_dancer, I was talking to the common user. I know ketone can be crystallied as I've said several timers in this thread. Generally though, your garden meth cook wont do it. Also, for the end user examining their product, therte is no difference you can see with the naked eye.

I do understand the possibilities, I was just trying to inform the general person that will be coming across this thread, and what they'll see

 

[phase_dancer]

Re: selegiline, I didn't know that it was considered that l-methamphetamine and l-amphetamine contributed major effects.

Despite the paper by Yasar et al, neurotoxicity associated with the L-meth has been noted in-vitro, suggesting that when selegiline was found to be non-neuroprotective in clinical trials, this was likely due to the major metabolite L-methamphetamine. [1,2]. Work by Ama et al demonstrated that L-methamphetamine blocked the neuroprotective properties of both selegiline and rasagiline. In contrast, the main metabolite of rasagiline (aminoindan), a non-sympathomimetic, did not inhibit the neuroprotective properties of either selegiline or rasagiline.

So it appears, and would be consistent with data indicating the toxicity of L-meth, that sufficient L-meth maybe produced from the metabolism of selegiline to induce neurotoxicity, or at least block some of the neuroprotective benefits of selegiline.

I can't find quantitative data for all the half lives of selegiline metabolites, however, it is noted (wiki) that initial or one off dosages of selegiline have a short half life (~9 hours). Desmethylselegiline also has a relatively short half life, with removal of the propargyl group resulting in amphetamine [3]. As stimulation is still felt well beyond this period, it must be concluded that L-meth and or L-amp are responsible.

I don't wish to imply the CNS activity of L-meth is anything like that of D-meth. We know l-meth is more of a NE releasing agent (at least at low dosages) whereas d-meth also significantly increases dopamine levels, so comments regarding peripheral stimulation with L-meth and it being less euphoric are to be expected. My points were that L-meth is active, and that post-first pass effects from taking selegiline (non-chronic dosages) are certainly noticeable, and these are attributed to L-meth and to a lesser degree L-amphetamine.


[1] Orit Bar Ama, b, Tamar Amita,b, Moussa B.H. Youdima,
Contrasting neuroprotective and neurotoxic actions of respective
metabolites of anti-Parkinson drugs rasagiline and selegiline
Neuroscience Letters 355 (2004) 169–172


[2] I. Shoulson, DATATOP: a decade of neuroprotective inquiry.
Parkinson Study Group. Deprenyl and tocopherol anti-oxidative
therapy of Parkinsonism, Ann. Neurol. 44 (1998 ) S160–S166.

[3] Masanori Hasegawaa, b, Kazuo Matsubarac ,*, Shoju Fukushimaa,
b a a Chikatoshi Maseda , Takashi Uezono , Kojiro Kimura
Stereoselective analyses of selegiline metabolites:
possible urinary markers for selegiline therapy

@ footscrazy: I understand, and I know I took Mr Blondes comments somewhat out of context, but isn't it better to properly inform someone? Half answers lead to half truths and we all know how many half truths there are in relation to drugs.

 

[Mr Blonde]

but isn't it better to properly inform someone? Half answers lead to half truths and we all know how many half truths there are in relation to drugs.

That is very true, and when I'm wrong then I want to be corrected. I was wrong in my suggestions regarding that perhaps it is not centrally acting, but obviously l-methamphetamine is not the same type of stimulant that the dextro isomer is.

That is interesting information regarding selegiline and neurotoxicity. I assume that neurotoxicity from l-meth must be due to similar mechanisms as with d-meth; metabolism of dopamine into reactive oxygen molecules by MAO. If selegiine is an MAO-B inhibitor, then I assume a lot of this metabolism must be undertaken by MAO-A. If l-methamphetamine is cancelling out this neuroprotective effect, there must be a substantial quantity of dopamine being released. Is this just happening at dopamine neurons not associated with reinforcing behavior, or is there another mechanism at play?

Also, I miss your posts p_d.

 

[belarki]

referenced posts in Aus DD? I think I just peed a little!

Good to see you still passing through on occasion p_d

 

[phase_dancer]

That is interesting information regarding selegiline and neurotoxicity. I assume that neurotoxicity from l-meth must be due to similar mechanisms as with d-meth; metabolism of dopamine into reactive oxygen molecules by MAO.

I think it's more complex than that. From what I can gather, the mechanisms associated with d-meth related axon toxicity are not likely to be those associated with the countering effects L-meth has on selegiline neuroprotection. L-meth is often referred to as non-neurotoxic in relation to dopamine neurons, transporters etc, however, I tend to question that with higher doses that are reportedly active at releasing dopamine. With d-meth, as you've indicated, toxicity involves peroxynitrite and other reactive oxygen species produced by (1) DA release and subsequent enzymatic oxidation, (2) DA auto-oxidation and (3) mitochondrial disruption. Glutamate response mechanisms also contribute [5] There are many cascading and associated response mechanisms involved*. It has been suggested microglial activation in the straitum may be involved with d-meth toxicity, which wasn't observed with L-meth. [4] The paper cited in my above post [1] involved experiments with PC12 cells deprived of serum and nerve growth factor. Normally these cells die from apoptosis (programmed cell death). When either selegiline or rasagaline was added, cell death was prevented, but when L-meth was also introduced, it blocked the neuroprotective actions of both drugs. In contrast, the rasagiline metabolite didn't block the protective effect of either. However, this shouldn't be taken to mean the L-meth metabolite completely negates the benefits of selegiline.

If selegiine is an MAO-B inhibitor, then I assume a lot of this metabolism must be undertaken by MAO-A. If l-methamphetamine is cancelling out this neuroprotective effect, there must be a substantial quantity of dopamine being released. Is this just happening at dopamine neurons not associated with reinforcing behavior, or is there another mechanism at play?

One thing to remember, is indirect acting sympathomimetics like amphetamine usually also affect other neurotransmitters. In the case of AMP, it's primarily a noradrenaline releaser (via uptake 1 inhibition), and a MAO inhibitor, but to a lesser also affects dopamine and degree serotonin.

I'm pretty sure d & l meth would be poor substrates for MAOA. The Km for phenethylamine bindings with MAOA and MAOB are 140+-22 & 4+- 2 respectively [6]. The addition of an alpha methyl group to phenethylamine (i.e. amphetamine) reduces binding (through inhibition and/or due to steric effects ?), and the addition of the N-methyl group (meth) reduces MAO oxidation even further (explaining the longer half). Aside from cytochrome actions, as mentioned, other oxidation routes come into play.

BTW, I made a mistake in the above post. Selegiline has a single use half life of 1.5 hours, and 9 for chronic dosages. As can be seen, as the principle inhibiting effect on MAOB becomes greater with repeated use, it takes longer to metabolise. Accordingly, this may or may not significantly extend the L-meth metabolite half life, depending on what other oxidative routes come into play.

[4]Microglial activation is a pharmacologically specific marker for the neurotoxic amphetamines. Thomas DM, Dowgiert J, Geddes TJ, Francescutti-Verbeem D, Liu X, Kuhn DM. Neurosci Lett. 2004 Sep 9;367(3):349-54.
http://www.ncbi.nlm.nih.gov/pubmed/15337264


[5]Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms
and relevance to human abuse and treatment
Colin Davidsona, Andrew J. Gowc, Tong H. Leea, Everett H. Ellinwooda,
Brain Research Reviews 36 (2001) 1–22

[6]The therapeutic potential of
monoamine oxidase inhibitors Nature Reviews, Neuroscience 2006, Table 1 | Substrate specificities of the monoamine oxidases in the cerebral cortex

*The full paper [5] is well worth a read if you can get it. There's probably also been additional findings on mechanisms of Meth toxicity published since...I've run out of time....Paper [6] is also very interesting.

@belarki. Maybe you should improve bladder function through encouraging more referencing

 

[Mr Blonde]

^ Thanks P_d, now that I'm working full-time I can probably afford to purchase access to some articles.

...toxicity involves peroxynitrite and other reactive oxygen species produced by (1) DA release and subsequent enzymatic oxidation, (2) DA auto-oxidation and (3) mitochondrial disruption.

OK, I was aware of DA release and oxidation, but am unsure on what DA-auto-oxidation is. Is that referring to non-enzymatic oxidation of DA, or another mechanism? Also, what is the nature of the mitochondrial disruption? I know that over time they are damaged as a result of their function in the electron transport chain; is methamphetamine increasing the quantity or quality of damage done in this process?

I'm pretty sure d & l meth would be poor substrates for MAOA

Sorry I wasn't clear, I meant to say DA is the substrate and that if the MAO-B pathway is blocked then MAO-A would be the pathway for enzymatic change. I thought that amphetamine and methamphetamine were poor substrates due to steric reasons, as enzymes tend to be more specific then receptors, but I can't remember where I read about that.

Phase, you only studied chemistry and not pharmacology or bio-med or anything right? I was just wondering if you had heard of a textbook called 'Selective Toxicity'. It's by an Australian named Adrian Albert, who was a lecturer at University of Sydney I think. I was recommended it for pharmacological reasons, but it also talks a lot about physiology, chemistry and biology and has gotten me a lot more interested in microbiology.

 

[phase_dancer]

Me Blonde - Check your PM.

I did a chem major w/bio-med electives incl biochem, anatomy and pharmacology. Microbiology is a fascinating subject these days, although there was a low first year pass rate when I was an undergrad (due to Biology). Things may have well changed today though, and I'm sure some of our current science students can give a better picture of that. If you decide to do pharmacology as a major, you'll still get to do some microbiology, chemistry, anatomy & physiology and a host of hands on lab subjects... all fun stuff!

I have heard of Adrien Albert, but have not read the book. I take it you mean "Selective toxicity: The physico-chemical basis of therapy"? I did find second hand copies on line - with some, incl freight, costs were less than a tener!

 

[Mr Blonde]

^ Yep, that's the one! Mine was 25 cents, plus three dollars postage from the library of St. John's University in New York.

It's a great read, I tried a few other books first and then a pharmacist recommended that one as Albert was his lecturer back in the day. It gives a great background on the chemistry, bio-chem and biology needed to understand chemotherapeutics and pharmacodynamics before delving into the actual drug action. I'm up to the chapter on chemistry of receptor bonding right now.

I did a chem major w/bio-med electives incl biochem, anatomy and pharmacology. Microbiology is a fascinating subject these days, although there was a low first year pass rate when I was an undergrad (due to Biology). Things may have well changed today though, and I'm sure some of our current science students can give a better picture of that. If you decide to do pharmacology as a major, you'll still get to do some microbiology, chemistry, anatomy & physiology and a host of hands on lab subjects... all fun stuff!

I'm looking at university programs right now, and the course I'm interested in definitely has all those in first year as well as medical statistics which is what I'll need to work on as maths has never been my strong suit. I've been doing some reading into dissociation constants and the like at the moment as I'm also interested in understanding some of the maths behind chemistry, though I am making slow progress.

 

[book of revelation]

referenced posts in Aus DD? I think I just peed a little!

Good to see you still passing through on occasion p_d

Correctly referenced too, I might add.

Well done, sir.


book rev

 

[pisspotnrock]

I've heard p2p(ketone) derived ice is more manageable, less fiendy and a better rounded high..


Also "ketone" can refer to methcathinone occasionally, but you'll know it when you get that shit.

R.I.P 'titstypedthis'..

I'm only aware of his passing today but his body was found in his room monday morning... I wasnt close to him but have chatted to him many a time over facebook and sent him a couple of things here n there, and vice-versa..

I know many of you didnt get along with him when he did post on this forum but his life was taken tragically at such a young age.. he was only 22 this year....

R.I.P Reece..

 

[Mr Blonde]

^ Sad to hear.

 

[laugh]

^^ respect

 

[drug_mentor]

Very sorry to hear of another BLer passing... R.I.P titstypedthis