Chemical Analysis of Neorg. Products
The following results stem from analysing 4 x samples, as received by the analytical chemists involved. Before discussing these results, a few points need to be mentioned.
The analytical procedures were carried out by experienced, qualified forensic chemists working in a NATA accredited laboratory. This is not a police department laboratory, but an independently run lab, the type which is contracted by agencies such as police and other investigative bodies.
These results are representative of the above mentioned samples. It's possible that the manufacturer/ supplier may have changed the formulae of these products since the time these samples were received. The products could also be packaged differently or may now contain different formulations. Variation in formulae may include:
* Addition of other compounds not found in tested samples
* Removal or replacement of one or more active compounds
* Reformulation of the determined compounds i.e. altered ratios of active compounds.
Procedures:
Analyses were accomplished using Gas Chromatography & Mass Spectral Detection (GC/MSD) for volatile and semi volatile organic compounds and Liquid chromatography and Mass Spectral Detection (LC/MSD) to determine molecular weight. Nuclear Magnetic resonance was used to elucidate the structure of one chemical, for which spectral data was unavailable.
Limitations:
As pure certified reference samples of the suspected compounds were not available, identification using GC/MSD can only be considered tentative. Interpretation of results from the above mentioned procedures has been independently assessed and conclusions validated.
Notification of Authorities:
Due to the illicit nature of 4 of the five compounds identified, authorities were informed of the outcomes of these tests. As far as I understand from the lab report, the products were identified solely by their appearance, and labeled from ‘xxxxxxx-1’ to ‘xxxxxxx-4’ (where ‘xxxxxxx-x’ is a case number or batch code). As the products were not sourced by the analysts, company and product names were not known, and so not stated on the official report.
Results:
Product xxxxxxx-1
Procedures used: Marquis presumptive test, GC/MSD, LC/MSD, NMR,
Reaction with Marquis Reagent produced a pale pink colour. Interpretation of spectral data indicated the presence of:
4-Methylmethcathinone
Structural description: 4-methylmethcathinone is a para-substituted, N-methyl cathinone.
Product xxxxxxx-2
Procedures used: Marquis presumptive test, GC/MSD, LC/MSD
Reaction with Marquis Reagent was considered relatively insignificant and produced a slightly yellow colour. Interpretation of spectral data indicated the presence of:
4-Fluoromethamphetamine
Structural description: 4-fluoromethamphetamine is a para-substituted, N-methylamphetamine
Phthalimidopropiophenone
Structural description: Phthalimidopropiophenone is a phthalimido derivative of cathinone.
Products xxxxxxx-3
&
Product xxxxxxx-4
Procedures used: Marquis presumptive test, GC/MSD, LC/MSD
It was concluded that products xxxxxxx-3 & xxxxxxx-4 contain the same active compounds, but in different proportions (quantitative data not provided).
Reaction with Marquis produced a pale orange colour, dissimilar to the colour produced from Marquis Reagent reaction with amphetamine. Results of spectral data indicate the presence of:
4-Methylmethcathinone (N-methyl-4-methylaminopropiophenone)
Metamfepramone
Phthalimidopropiophenone
Caffeine
Comments
There exists little to no pharmacological data for many of these compounds. Where possible some comparisons have been made with similarly structured compounds. It needs to be emphasised though, that in such cases, the following comments are only speculative. However, while the toxicicological profiles for some of these chemicals are still in doubt, it is still worth carefully considering whether, in some cases, there is significant potential for impact on user health and wellbeing. Hopefully, other contributers will be able to further enlighten us on the pharmacology of these compounds.
Compound:
4-methylmethcathinone
Legal: Under Australian law, in most states 4-Methylmethcathinone can be considered an analogue of the scheduled (illicit) drug methcathinone.
Pharmacological: 4-Methylmethcathinone is sympathomimetic stimulant. From proposed SAR modelling, 4-methylmethcathinone is expected to have similar pharmacological properties to methcathinone, but with increased activity on the serotonin neurotransmitter systems. Methcathinone is suggested as being more potent than its parent cathinone, and methamphetamine (1)
Methcathinone is a drug with a high abuse potential, with prolonged, high dosages known to cause psychosis and withdrawal tremors. Methcathinone is regarded as being similar in profile to methamphetamine in relation to neurotoxicity, with marked decreases in DA levels noted among abstinent users. While generally below levels associated with Parkinsons Disease, this is considered to be demonstrative of permanent, or semi permanent neurological damage (2)
Quote:
Compared with controls, abstinent methamphetamine
and methcathinone users had significant decreases in
DAT density in the caudate nucleus (223 and 224%, respectively)
and putamen (225 and 216%, respectively).
It can be speculated that the para substituted compound 4-methylmethcathinone may have reduced stimulant activity, but as said, its likely to have additional affect on serotonin via both monoamine reuptake/ SERT inhibition and direct agonist affects of the 5HT2b receptors. Concerns have been raised regarding the actions of 4-methylmethcathinone in relation to peripheral 5HT (serotonin) stimulation and how that, combined with other catecholamine activity, may be dangerous to the heart.
In a similar manner to which pulmonary hypertension is caused by peripheral 5HT produced by gastrointestinal carcinoid tumours (and some argue 5HTP), other 5HT2b agonists have been found to cause this effect, which would be exacerbated by increased DA/NE levels and their corresponding affect on the heart. Longer term, such stimulation has been shown to result in fibroblast mitosis of the mitral valve of the left atrium (specifically the Chordae Tendineae). (3,4)
While it has yet to be demonstrated by means of scientific study that 4-methylmethcathinone produces these effects, I believe it's wise to consider carefully the possible toxicity of this compound if you're intending to ingest or otherwise consume products containing this drug.
Compound:
4-Fluoromethamphetamine
Legal: Under Australian law, in most states 4-Fluoromethamphetamine can be considered an analogue of the scheduled (illicit) drug Methamphetamine.
Pharmacological: From what I can gather, this compound has not been widely researched. However, the parent compound 4-fluoroamphetamine has been evaluated and compared to other halo amphetamines. While the 4-bromo and 4-chloro amphetamines significantly affect serotonin levels, 4-fluoramphetamine has been found to have minimal effect on 5HT, and contrary to the other halogens, levels are restored within days of use.
Some concern has been raised regarding potential pulmonary toxicity of the N-methyl analogue, if this compound is a 5HT2b agonist. N-methyl-4-fluoroamphetamine may also have a significantly different neurotoxicity profile than the parent compound (as per methamphetamine when compared to amphetamine) and if meth is anything to go by, will possibly also have increased actions on the 5HT system.
N-methyl-4-fluoroamphetamine has been noted in Forensic literature (5)
Compound:
Metamfepramone
Legal: Under Australian law, in most states Metamfepramone can be considered an analogue of the scheduled (illicit) drug Methcathinone
Pharmacological: It has been reported (thanks f&b) that Metamfepramone was once used clinically as an anoretic, although use was ceased due to the abuse potential being higher than with diethylpropion, the N-ethyl homologue, also known as Tenuate Dospan. While Tenuate is less euphoric than Metamfepramone, it too was removed from prescription in Australia and NZ around the early 1980’s for similar reasons.
Both Metamfepramone and Tenuate are thought to metabolise in a similar manner.
Quote:
METHYLEPHEDRINE FINDINGS AFTER INTAKE OF METAMFEPRAMONE - STUDIES ON THE METABOLISM AND THE TOXICOLOGICAL DETECTION OF METAMFEPRAMONE USING GC-MS
Thomas Kraemer, Negar Makkinejad, and Hans H. Maurer
Institute of Pharmacology and Toxicology, Department of Toxicology, University of Saarland, D-66421 Homburg (Saar), Germany
Methylephedrine (ME), a sympathomimetic amine, is ingredient of many over-the-counter cold medications. ME abuse has been reported in some asian countries. Kunsman et al. reported ME findings in drug testing samples in the U.S.A. (1). In our lab, ME was found in urine of patients denying its intake. The only known medication was metamfepramone (R,S-2-dimethylaminopropiophenone, MP), a sympathomimetic used as antihypotonic or as cold medication. To study, whether and how long ME, methylpseudoephedrine, ephedrine (EP) and/or pseudoephedrine (PE) can be detected in urine after intake of MP, we reinvestigated the metabolism of MP, its detection within our STA procedure and the duration of detectability.
The metabolites were identified in urine after cleavage of conjugates, extraction and derivatization by acetylation using GC-MS. Besides the parent compound, the following metabolites could be identified in urine: ME, EP, PE, nor-EP, nor-MP, hydroxy-nor-MP and hydroxy-nor-EP. Differentiation of the ME and EP diastereomers was achieved after trifluoroacetylation. Three partly overlapping metabolic pathways could be postulated: 1) reduction of the ketogroup, 2) one- and two-fold N-demethylation and 3) ring hydroxylation.
After intake of 20 mg of MP, its main metabolite ME could be detected for about 140 h, EP and PE for about 132 h (n = 3). Nor-MP, the MP specific metabolite could only be detected for about 52 h. Therefore, in the time window from 52 to 140 h differentiation of MP intake from ME, EP and/or PE use was not possible. The analytical recoveries were 55 % for MP, 98 % for ME and 75 % for PE and the LOD's were 50 ng/mL for MP and 10 ng/mL for ME, EP and PE.
1. G.W. Kunsman, R. Jones, B. Levine and M.L. Smith; Methylephedrine Concentrations in Blood and Urine Specimens, Abstracts to the SOFT annual meeting, October 5-9, 1997, Utah
From here
Quote:
Diethylpropion [Tenuate Dospan]
Disposition in the Body.
Readily absorbed after oral administration. Metabolised by N-dealkylation, reduction, deamination, and N-hydroxylation primarily to active metabolites; keto reduction is stereoselective resulting in the formation of threo–hydroxylated metabolites; glucuronide formation also occurs along with the formation of hippuric and mandelic acids. About 80 to 90% of a dose is excreted in the urine; the amount excreted in the urine is reduced when the urine is alkaline; of the urinary excreted material, N-ethylaminopropiophenone, norephedrine (phenylpropanolamine), and hippuric acid are the main metabolites together with small amounts of unchanged drug, aminopropiophenone, N-diethylnorephedrine, and N-ethylnorephedrine. Diethylpropion crosses the blood–brain barrier and the placenta. The drug and its metabolites are distributed into breast milk.
Therapeutic concentration
Following a single oral dose of 75 mg to 5 subjects, a mean peak plasma concentration of 0.007 mg/L was attained in 0.5 h; total concentrations of the monodesethyl and didesethyl metabolites reached an average peak of 0.19 mg/L at 2 h. [G. J. Wright et al.,Drug Metab. Rev.,1975, 4, 267–276.]
Toxicity.
The estimated minimum lethal doses are 200 mg for a child and 2 g for an adult.
The following disposition was reported in a case of fatal overdose resulting from the injection of illicit diethylpropion tablets: blood 5.4 mg/L, bile 14.4 mg/L, kidney 0.9 ?g/g, liver 0.9 ?g/g, injection site 43.2 ?g/g. [R. R. Fysh and J. F. Taylor,Bull. Int. Assoc. Forensic Toxicol.,1978, 142, 16–17.]
Half–life.
Derived from urinary excretion data, 1.5 to 3 h in subjects whose urines are acidic.
From Clarke’s Analysis of Drugs and Poisons
Compound:
Phthalimidopropiophenone
Legal: Under Australian law, if Phthalimidopropiophenone produces an illict drug in-vivo, this compound is considered a pro-drug and as such covered by analogue legislation as applies to most states.
Chemistry: A known method of producing amines (including beta-keto amines) is to react an alkyl halide with potassium phthalimide (which is itself made from phthalic anhydride and ammonia). The reaction is known as the Gabriel Synthesis of primary amines. Normally, then phthalimido compound is subjected to either acid or alkali hydrolysis to cleave off the phthalate ion and release the amine either as a salt (acid) or a free base (alkali, hydrazine).
One thing I’ve not mentioned so far concerns the shelf life of cathinones. Cathinones with a secondary or tertiary amine are far more stable than is cathinone itself, which has been noted to sometimes form a cyclization product when being synthesized, and age to form a dimer like product when left standing.
Cleaving the phthalimido group in the lab therefore not only results in a product with a short shelf life, but is also known for producing side reaction products. In short, it’s messy, with the best method considered to be to use hydrazine, and hydrazine is not nice to work with. Also, by leaving the group attached, the free amine is essentially ‘hidden’, and so its thought this would help to mask an already illicit substance.
Pharmacological: A range of prodrugs incorporating a GABA-phthalimide structure have been developed, in particular, for applications in the treatment of epilepsy. One question is; can the phthalimido group be adequately cleaved in the stomach? Acid hydrolysis is normally a very slow process, but it’s been suggested that this may be hastened via enzymatic activity or be performed completely by pyramidinases enzymes (thanks vecktor). Concerns to health include the metabolic elimination of the phthalate ion/ phthalic acid, particularly with prolonged use, and the possible impacts if cleavage occurs in sensitive organs. If hydrolysis does occur in the stomach, then it might explain how effects differ with different routes of administration. Either way, it’s expected the rate at which cleavage occurs would be slow, and may explain the noted changing of effects over several hours.
Compound:
Caffeine
Legal: Legal under Australian law
There's much information available on the effect of caffeine. Caffeine is known to have effect on the absorption of some drugs and drug combinations (6). For further info on Caffeine, a good place to start is Erowid
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Much has not been covered in this post. We have not considered isomers of these compounds and their variations in effects, impurities from synthesis, possibility of interactions with other drugs, etc.....
Refs
1) Martin D Schechter; Drug-Drug Discrimination: Stimulus Properties of Drugs of Abuse Upon a Serotonergic-Dopaminergic Continuum; Pharmacology Biochemistry and Behavior Volume 56, Issue 1, January 1997, Pages 89-96
2) Una D. McCann, Dean F. Wong, Fuji Yokoi, Victor Villemagne, Robert F. Dannals, and George A. Ricaurte; Reduced Striatal Dopamine Transporter Density in Abstinent Methamphetamine and Methcathinone Users: Evidence from Positron Emission Tomography Studies with [11C]WIN-35,428; The Journal of Neuroscience, October 15, 1998, 120):8417–8422
3) Takafumi Nagatomo, Mamunur Rashid, Habib Abul Muntasir and Tadazumi Komiyama; Functions of 5-HT2A receptor and its antagonists in the cardiovascular system; Pharmacology & Therapeutics Volume 104, Issue 1, October 2004, Pages 59-81
4) Bluelight post
http://www.bluelight.ru/vb/showpost....47&postcount=9 and thread
http://www.bluelight.ru/vb/showthread.php?t=287832
5) Peter Ro¨sner, Bernd Quednow, Ulrich Girreser, Thomas Junge; Isomeric Fluoro-methoxy-phenylalkylamines: a new series of controlled-substance analogues (designer drugs); Forensic Science International 148 (2005) 143–156
6) Bluelight thread: Article on Interactions between common MDMA substitutes affecting absorption
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Comments, criticisms etc on the above are most encouraged.
I would like to extend a big thanks to the numerous Bluelighters and Non-Blers who assisted with this project. Without the parts you've all played, it simply wouldn't have happened.
With this report, HR Australia sends a simple message to all manufacturers and suppliers of psychoactive products; List the ingredients of your products.
I would like to think these outcomes will provide a convincing argument towards providing an analytical service that can evaluate, scrutinize and validate all such products, ranging from health to pharmaceuticals to everything that lies in between.
