GC–MS and GC–IRD analysis of 2-, 3- and 4-methylmethamphetamine and 2-, 3- and 4-methylamphetamine

Davis, Sean A.; Blakey, Karen; Rands-Trevor, Karen

doi:10.1016/j.forsciint.2012.01.028

Cited by 18 publications

(13 citation statements)

References 19 publications

(30 reference statements)

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“…(R,S)-N-Methcathinone HCl was obtained from the NIDA Research Resources Drug Supply Program. Racemic 4MM was synthesized as described by Davis et al (2012) from methylamine HCL and 4-methylphenylacetone purchased from Alfa Aesar (ThermoFisher Scientific, Tewksbury, MA), and its structure was confirmed by NMR and mass spectrometry. DA, polyclonal antibodies against glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and all buffers and high-performance liquid chromatography reagents were purchased from Sigma-Aldrich (St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

Dissecting the Influence of Two Structural Substituents on the Differential Neurotoxic Effects of Acute Methamphetamine and Mephedrone Treatment on Dopamine Nerve Endings with the Use of 4-Methylmethamphetamine and Methcathinone

Anneken

Angoa‐Pérez

Sati

et al. 2016

J Pharmacol Exp Ther

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Mephedrone (MEPH) is a b-ketoamphetamine stimulant drug of abuse that is often a constituent of illicit bath salts formulations. Although MEPH bears remarkable similarities to methamphetamine (METH) in terms of chemical structure, as well as its neurochemical and behavioral effects, it has been shown to have a reduced neurotoxic profile compared with METH. The addition of a b-keto moiety and a 4-methyl ring substituent to METH yields MEPH, and a loss of direct neurotoxic potential. In the present study, two analogs of METH, methcathinone (MeCa) and 4-methylmethamphetamine (4MM), were assessed for their effects on mouse dopamine (DA) nerve endings to determine the relative contribution of each individual moiety to the loss of direct neurotoxicity in MEPH. Both MeCa and 4MM caused significant alterations in core body temperature as well as locomotor activity and stereotypy, but 4MM was found to elicit minimal dopaminergic toxicity only at the highest dose. By contrast, MeCa caused significant reductions in all markers of DA nerve-ending damage over a range of doses. These results lead to the conclusion that ring substitution at the 4-position profoundly reduces the neurotoxicity of METH, whereas the b-keto group has much less influence on this property. Although the mechanism(s) by which the 4-methyl substituent reduces METH-induced neurotoxicity remains unclear, it is speculated that this effect is mediated by a loss of DA-releasing action in MEPH and 4MM at the synaptic vesicle monoamine transporter, an effect that is thought to be critical for METH-induced neurotoxicity.

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Section: Methodsmentioning

confidence: 99%

Dissecting the Influence of Two Structural Substituents on the Differential Neurotoxic Effects of Acute Methamphetamine and Mephedrone Treatment on Dopamine Nerve Endings with the Use of 4-Methylmethamphetamine and Methcathinone

Anneken

Angoa‐Pérez

Sati

et al. 2016

J Pharmacol Exp Ther

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“…These pathways indicate that the regioisomers 2-and 3-methylamphetamine present the same mass spectral fragments. Davis et al studied the mass spectrum of 2-, 3-and 4-methylamphetamine and their N-acetyl derivatives and concluded that other analytical techniques are needed to identify the correct regioisomer of a methyl ringsubstituted amphetamines [3]. This is a drawback when identification of the specific regioisomers is a legislative requirement.…”

Section: Discussionmentioning

confidence: 99%

“…The Correspondence: Jan Cordonnier, jan.cordonnier@chemiphar.com structure elucidation by gas chromatography mass spectrometry (GC/MS) and nuclear nuclear magnetic resonance spectroscopy (NMR) was described by Westphal et al [2]. The GC/MS analysis and gas chromatography-infrared detection of 2-, 3-and 4-methylmethamphetamine and 2-, 3-and 4-methylamphetamine was reported by Davis et al [3].…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic characterization of 4-methylamphetamine: formaldehyde adduct formation hindered the identification by mass spectrometry

Coopman¹,

Delbeke²,

Ingelgem³

et al. 2012

Ann Toxicol Anal

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-A powder was submitted to the author's laboratory for analysis on the presence of illegal drugs. Based on the structure elucidation performed by nuclear nuclear magnetic resonance spectroscopy and analysis of the trimethylsilyl and trifluoroacetyl derivatives with gas chromatography mass spectrometry, the powder was found to contain the designer drugs 4-methylamphetamine, besides amphetamine and caffeine. The electron impact mass spectrum of 4-methylamphetamine obtained from the analysis of a methanolic sample solution showed a base ion of m/z 56 rather than the expected m/z 44, therefore no hit was found with an electron impact mass spectrum present in the mass spectral library and literature. The increase of 12 atomic mass units was explained by formaldehyde-adduct formation.Key words: 4-methylamphetamine, formaldehyde, mass spectrometry Résumé -Une poudre a été soumise au laboratoire de l'auteur pour analyse quant à la présence de drogues illégales. Sur base de l'explication de structure exécutée par la spectroscopie de résonance magnétique nucléaire et l'analyse du trimethylsilyl et les dérivés du trifluoroacétyle par la chromatographie en phaze gazeuse avec la spectrométrie de masse comme détection, il a été découvert que la poudre contenait de la drogue synthétique 4-methylamphétamine, en plus de l'amphétamine et de la caféine. Le spectre de masse d'impact électronique de 4-methylamphétamine obtenu par l'analyse d'une solution d'échantillon méthanolique a démontré un ion de base de m/z 56 plutôt que le m/z 44 attendu. Par conséquent, aucun résultat n'a été trouvé contenant un spectre de masse d'impact électronique présent dans la bibliothèque spectrale de masse et littérature. L'augmentation de 12 unités atomiques de masse a été expliquée par la formation d'adduit de formaldéhyde.

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“…Racemic 4-methlymethamphetamine HCl was synthesized as described by Davis et al (2012) from methylamine HCl and 4-methylphenylacetone purchased from Alfa Aesar (Ward Hill, MA, USA). (+)- Methamphetamine HCl, pargyline HCl, L-3,4-dihydroxyphenylalanine (L-DOPA), S-(−)-carbidopa, DA, polyclonal antibodies against glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and all buffers and HPLC reagents were purchased from Sigma-Aldrich (St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Assessing the role of dopamine in the differential neurotoxicity patterns of methamphetamine, mephedrone, methcathinone and 4-methylmethamphetamine

et al. 2018

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Methamphetamine and mephedrone are designer drugs with high abuse liability and they share extensive similarities in their chemical structures and neuropharmacological effects. However, these drugs differ in one significant regard: methamphetamine elicits dopamine neurotoxicity and mephedrone does not. From a structural perspective, mephedrone has a β-keto group and a 4-methyl ring addition, both of which are lacking in methamphetamine. Our previous studies found that methcathinone, which contains only the β-keto substituent, is neurotoxic, while 4-methylmethamphetamine, which contains only the 4-methyl ring substituent, elicits minimal neurotoxicity. In the present study, it was hypothesized that the varying neurotoxic potential associated with these compounds is mediated by the drug-releasable pool of dopamine, which may be accessed by methamphetamine more readily than mephedrone, methcathinone, and 4-methylmethamphetamine. To test this hypothesis, L-DOPA and pargyline, compounds known to increase both the releasable pool of dopamine and methamphetamine neurotoxicity, were combined with mephedrone, 4-methylmethamphetamine and methcathinone. Methamphetamine was also tested because of its ability to increase releasable dopamine. All three regimens significantly enhanced striatal neurotoxicity and glial reactivity for 4-methylmethamphetamine. Methcathinone neurotoxicity and glial reactivity were enhanced only by L-DOPA. Mephedrone remained non-neurotoxic when combined with either L-DOPA or pargyline. Body temperature effects of each designer drug were not altered by the combined treatments. These results support the conclusion that the neurotoxicity of 4-methylmethamphetamine, methcathinone and methamphetamine may be differentially regulated by the drug-releasable pool of dopamine due to β-keto and 4-methyl substituents, but that mephedrone remains non-neurotoxic despite large increases in this pool of dopamine.

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GC–MS and GC–IRD analysis of 2-, 3- and 4-methylmethamphetamine and 2-, 3- and 4-methylamphetamine

Cited by 18 publications

References 19 publications

Dissecting the Influence of Two Structural Substituents on the Differential Neurotoxic Effects of Acute Methamphetamine and Mephedrone Treatment on Dopamine Nerve Endings with the Use of 4-Methylmethamphetamine and Methcathinone

Dissecting the Influence of Two Structural Substituents on the Differential Neurotoxic Effects of Acute Methamphetamine and Mephedrone Treatment on Dopamine Nerve Endings with the Use of 4-Methylmethamphetamine and Methcathinone

Spectroscopic characterization of 4-methylamphetamine: formaldehyde adduct formation hindered the identification by mass spectrometry

Assessing the role of dopamine in the differential neurotoxicity patterns of methamphetamine, mephedrone, methcathinone and 4-methylmethamphetamine

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