Molecular Connectivity Analysis of Hallucinogenic Mescaline Analogs

Glennon, Richard A.; Kier, Lemont B.; Shulgin, Alexander T.

doi:10.1002/jps.2600680733

Cited by 26 publications

(13 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…He synthesized many representatives and described their action on the body in the book PIHKAL, Phenethylamines I Have Known And Loved . Typically, a 2C‐series member carries a lipophilic substituent in the para position relative to the side chain, which further enhances the 5‐HT 2A affinity and partial agonistic activity . The most active compounds identified to date possess an ether, alkylthio, alkyl, or halogen group at this position and potency increases in the aforementioned sequence .…”

Section: Introductionmentioning

confidence: 99%

“…[15] Typically, a 2C-series member carries a lipophilic substituent in the para position relative to the side chain, which further enhances the 5-HT 2A affinity and partial agonistic activity. [16][17][18][19][20][21][22] The most active compounds identified to date possess an ether, alkylthio, alkyl, or halogen group at this position and potency increases in the aforementioned sequence. [22][23][24] The popular representatives were: 2C-B (4-bromo-2,5-dimethoxy-b-phenethylamine), 2C-I (4-iodo-2,5-dimethoxy-b-phenethylamine), 2C-T-2 (4-ethylthio-2,5-dimethoxy-b-phenethylamine) and 2C-T-7 (2,5-dimethoxy-4-propylthio-b-phenethylamine).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Analytical characterization of three hallucinogenic N‐(2‐methoxy)benzyl derivatives of the 2C‐series of phenethylamine drugs

Zuba

Sekuła

2012

Drug Testing and Analysis

View full text Add to dashboard Cite

This publication reports analytical properties of three new hallucinogenic substances identified in blotter papers seized from the drug market, namely 25D-NBOMe [2-(2,5-dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine], 25E-NBOMe [2-(4-ethyl-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine] and 25G-NBOMe [2-(2,5-dimethoxy-3,4-dimethylphenyl)-N-(2-methoxybenzyl)ethanamine]. These substances are N-(2-methoxy)benzyl derivatives of the 2C-series of phenethylamine drugs. The applied procedure covered a variety of analytical methods, including gas chromatography with electron impact mass spectrometry (GC-EI-MS; without derivatization and after derivatization with trifluoroacetic anhydride (TFAA)), liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry (LC-ESI-QTOF-MS), Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR), which made it possible to identify the active components unequivocally. The GC-MS spectra of analyzed compounds were very similar, with dominant ions observed at m/z = 150, 121, and 91. The remaining ions were analogous to those observed for parent substances, namely 2C-D, 2C-E, 2C-G, but their intensities were low. Derivatization allowed determination of molecular masses of the investigated substances. Their exact masses and chemical formulas were confirmed by LC-QTOF-MS experiments and the fragmentation patterns of these compounds following ESI were determined. The tandem mass spectrometry (MS/MS) experiments confirmed that the studied substances were N-(2-methoxy)benzyl derivatives of the 2C-series compounds. Final elucidation of the structures was performed by NMR spectroscopy. The substances were also characterized by FTIR spectroscopy to corroborate the identity of the compounds.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analytical characterization of three hallucinogenic N‐(2‐methoxy)benzyl derivatives of the 2C‐series of phenethylamine drugs

Zuba

Sekuła

2012

Drug Testing and Analysis

View full text Add to dashboard Cite

show abstract

“…Activation of the 5‐HT2A (serotonin‐2A) receptors has been established as the key pharmacological action of these drugs . Structure‐activity relationship (SAR) studies have demonstrated that substituents in the para‐position relative to the side chain exert a marked effect on hallucinogenic activity . The most active compounds identified to date possess an alkyl, alkylthio or halogen group at position 4.…”

Section: Introductionmentioning

confidence: 99%

“…[20] Structure-activity relationship (SAR) studies have demonstrated that substituents in the para-position relative to the side chain exert a marked effect on hallucinogenic activity. [21][22][23][24][25][26][27] The most active compounds identified to date possess an alkyl, alkylthio or halogen group at position 4. Potency increases in the substituent sequence: H < OR < SR < R < halogen.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of 2,5‐dimethoxy‐3,4‐dimethyl‐β‐phenethylamine (2C‐G) – A new designer drug

Zuba

Sekuła

2012

Drug Testing and Analysis

View full text Add to dashboard Cite

This study presents and discusses the mass spectrometric, infrared spectroscopic and nuclear magnetic resonance spectroscopic data of 2,5-dimethoxy-3,4-dimethyl-β-phenethylamine (2C-G), a new designer drug. A powder sample containing 2C-G was seized in Poland in 2011. The paper focuses on a comparison of the analytical features of 2C-G and other members of the 2C-series, in order to assess the possibility of unequivocal identification. The occurrence of intense peak at m/z = 178 and different intensities of the ions at m/z = 165 and 180 in the gas chromatography-electron impact-mass spectrometry (GC-EI/MS) spectrum of 2C-G made it possible to distinguish it from 2C-E. Differences in relative intensities of the ions at m/z = 192, 179 and 177 were observed for GC-EI/MS spectra of TFAA derivatives of 2C-G and 2C-E. An identical set of ions was recorded for these substances using the liquid chromatography-electrospray ionization/quadrupole time of flight mass spectrometry (LC-ESI/QTOFMS) method in both MS and tandem mass spectrometry (MS/MS) mode, but the distinction was possible based on differences in the ion intensities at m/z = 193.1223 and 178.0988. The Fourier transform infrared (FTIR) spectrum of 2C-G was significantly different from other members of the 2C-series, with a characteristic doublets at 993-1014 cm(-1) and 1099-1124 cm(-1) , and the ratio of bands at higher wavenumbers. Final elucidation of the structure of 2C-G was carried out by (1) H and (13) C NMR spectroscopy. The study indicated that the marketing of analogues of controlled substances poses a real analytical challenge for forensic laboratories, and the application of sophisticated methods is often required for unequivocal identification of a new substance.

show abstract

“…Moreover, the homologation of any of the currently known phenylethylamines to their corresponding amphetamine analogues was found to increase dramatically the in vivo potency [121]. For this reason, the pharmacological characterization of mescaline analogues (mescalinoids) has not been extensively attempted and has remained rather restricted to their hallucinogenic action [152-154] or to the differences between hallucinogens and entactogens in vivo , where mescaline is included in the hallucinogenic category [155]. Moreover, none of the already characterized mescaline analogues has been included in the Designer Drugs Directory [156], so they are not considered “street drugs” and their individual subjective effects have not been investigated systematically.…”

Section: Mescalinoidsmentioning

confidence: 99%

MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology

Sáez-Briones

Hernández

2013

View full text Add to dashboard Cite

Besides stimulants and hallucinogens, whose psychotropic effects are shared by many structurally related molecules exhibiting different efficacies and potencies in humans, the phenylisopropylamine MDMA (3,4-methylenedioxymethamphetamine, XTC, “Ecstasy”) is the prototypical representative of a separate class of psychotropic substance, able to elicit the so-called entactogenic syndrome in healthy humans. This reversible altered state of consciousness, usually described as an “open mind state”, may have relevant therapeutic applications, both in psychotherapy and as a pharmacological support in many neuropsychiatric disorders with a high rate of treatment failure. Nevertheless, a comprehensive and systematic exploration of the structure-activity relationships associated with entactogenic activity has remained incomplete and controversial, highlighting the possibility that MDMA might represent a pharmacological rarity in the field of psychotropics. As the latter is still an open question, the pharmacological characterization of MDMA analogues remains the logical strategy to attempt the elucidation of the structural requirements needed to elicit typical MDMA-like effects. Intriguingly, almost no experimental evidence supports the existence of actual MDMA analogues that truly resemble the whole pharmacological profile of MDMA, probably due to its complex (and partially not fully understood) mechanism of action that includes a disruption of monoaminergic neurotransmission. The present review presents a brief summary of the pharmacology of MDMA, followed by the evidence accumulated over the years regarding the characterization of classical structurally related MDMA analogues in different models and how this state of the art highlights the need to develop new and better MDMA analogues.

show abstract

Molecular Connectivity Analysis of Hallucinogenic Mescaline Analogs

Cited by 26 publications

References 7 publications

Analytical characterization of three hallucinogenic N‐(2‐methoxy)benzyl derivatives of the 2C‐series of phenethylamine drugs

Analytical characterization of three hallucinogenic N‐(2‐methoxy)benzyl derivatives of the 2C‐series of phenethylamine drugs

Identification and characterization of 2,5‐dimethoxy‐3,4‐dimethyl‐β‐phenethylamine (2C‐G) – A new designer drug

MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology

Contact Info

Product

Resources

About