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1.
ACS Chem Neurosci ; 9(10): 2448-2458, 2018 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-29847089

RESUMO

Archeological studies in the United States, Mexico, and Peru suggest that mescaline, as a cactus constituent, has been used for more than 6000 years. Although it is a widespread cactus alkaloid, it is present in high concentrations in few species, notably the North American peyote ( Lophophora williamsii) and the South American wachuma ( Trichocereus pachanoi, T. peruvianus, and T. bridgesii). Spanish 16th century chroniclers considered these cacti "diabolic", leading to their prohibition, but their use persisted to our days and has been spreading for the last 150 years. In the late 1800s, peyote attracted scientific attention; mescaline was isolated, and its role in the psychedelic effects of peyote tops or "mescal buttons" was demonstrated. Its structure was established by synthesis in 1929, and alternative routes were developed, providing larger amounts for pharmacological and biosynthetic research. Although its effects are attributed mainly to its action as a 5-HT2A serotonin receptor agonist, mescaline binds in a similar concentration range to 5-HT1A and α2A receptors. It is largely excreted unchanged in human urine, and its metabolic products are apparently unrelated to its psychedelic properties. Its low potency is probably responsible for its relative neglect by recreational substance users, as the successful search for structure-activity relationships in the hallucinogen field focused largely on finding more potent analogues. Renewed interest in the possible therapeutic applications of psychedelic drugs may hopefully lead to novel insights regarding the commonalities and differences between the actions of individual classic hallucinogens.


Assuntos
Alucinógenos/química , Alucinógenos/farmacologia , Mescalina/química , Mescalina/farmacologia , Alucinógenos/história , Alucinógenos/uso terapêutico , História do Século XVI , História do Século XIX , História do Século XX , História do Século XXI , História Antiga , Humanos , Mescalina/história , Mescalina/uso terapêutico , Relação Estrutura-Atividade
2.
Drug Test Anal ; 10(1): 72-80, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28851034

RESUMO

This article describes the context in which 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and other mescaline-like compounds were explored as hallucinogens for military and intelligence purposes from the 1940s to the 1960s. Germans first tested mescaline as a "truth drug" in a military context. In the 1940s, the United States military started testing hallucinogenic substances as truth drugs for interrogation and behavior manipulation. After tests carried out using mescaline and other drugs in 1950, some derivatives of mescaline were synthesized by the Army for the exploration of possible "speech-inducing" effects. After insufficient animal testing, the substances were given to patients at the New York State Psychiatric Institute (NYSPI). 3,4-Methylenedioxy-N-ethylamphetamine (MDE), a compound almost identical to MDMA, was among the compounds delivered for testing at the NYSPI. During tests with other derivatives (3,4-dimethoxyphenethylamine (DMA), 3,4-methylenedioxyphenethylamine (MDPEA), MDA) in 1952-53, an unwitting patient died in these tests, which was kept secret from the public. Research was interrupted and toxicological animal testing procedures were initiated. The secret animal studies run in 1953/1954 revealed that some of the "mescaline derivatives" tested (e.g. MDA, MDE, DMA, 3,4,5-trimethoxyamphetamine (TMA), MDMA) were considered for further testing in humans. In 1955, the military changed focus to lysergic acid diethylamide (LSD), but some interest in mescaline-like compounds remained for their ability to change mood and habit without interfering with cognition and sensory perception. Based on the known documents, it remains unclear (but probable) whether any of the mescaline derivatives tested were being used operationally.


Assuntos
3,4-Metilenodioxianfetamina/administração & dosagem , Drogas Desenhadas/administração & dosagem , Alucinógenos/administração & dosagem , Mescalina/administração & dosagem , Militares/psicologia , N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem , Animais , Drogas Desenhadas/química , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/tendências , Alucinógenos/química , Humanos , Mescalina/química , N-Metil-3,4-Metilenodioxianfetamina/química , Estados Unidos , II Guerra Mundial
3.
J Forensic Sci ; 61 Suppl 1: S226-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27405021

RESUMO

Lophophora williamsii (peyote) is a small, spineless, greenish-blue cactus found in Mexico and the southwestern United States. Ingestion of the cactus can result in hallucinations due to its content of mescaline. In the United States, L. williamsii is classified as a Schedule I controlled substance. In this study, we use DNA analysis of the chloroplast trnL/trnF region and chloroplast rbcL gene to identify the individuals of Lophophora. Using the rbcL gene, Lophophora specimens could be distinguished from outgroups, but species within the genus could not be distinguished. The trnL/trnF region split the Lophophora genus into several groups based on the length and substructure of an AT-rich segment of the sequence. Our results indicate that the genetic variability at the trnL/trnF locus is greater than previously recognized. Although DNA structures at the trnL/trnF region and rbcL gene do not align with the classification of Lophophora species, they can be used to aid in forensic analysis.


Assuntos
DNA de Cloroplastos , Mescalina/química , Análise de Sequência de DNA , Ciências Forenses , Humanos , México , Filogenia
4.
BMC Genomics ; 16: 657, 2015 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-26330142

RESUMO

BACKGROUND: Lophophora williamsii (commonly named peyote) is a small, spineless cactus with psychoactive alkaloids, particularly mescaline. Peyote utilizes crassulacean acid metabolism (CAM), an alternative form of photosynthesis that exists in succulents such as cacti and other desert plants. Therefore, its transcriptome can be considered an important resource for future research focused on understanding how these plants make more efficient use of water in marginal environments and also for research focused on better understanding of the overall mechanisms leading to production of plant natural products and secondary metabolites. RESULTS: In this study, two cDNA libraries were generated from L. williamsii. These libraries, representing buttons (tops of stems) and roots were sequenced using different sequencing platforms (GS-FLX, GS-Junior and PGM, respectively). A total of 5,541,550 raw reads were generated, which were assembled into 63,704 unigenes with an average length of 564.04 bp. A total of 25,149 unigenes (62.19 %) was annotated using public databases. 681 unigenes were found to be differentially expressed when comparing the two libraries, where 400 were preferentially expressed in buttons and 281 in roots. Some of the major alkaloids, including mescaline, were identified by GC-MS and relevant metabolic pathways were reconstructed using the Kyoto encyclopedia of genes and genomes database (KEGG). Subsequently, the expression patterns of preferentially expressed genes putatively involved in mescaline production were examined and validated by qRT-PCR. CONCLUSIONS: High throughput transcriptome sequencing (RNA-seq) analysis allowed us to efficiently identify candidate genes involved in mescaline biosynthetic pathway in L. williamsii; these included tyrosine/DOPA decarboxylase, hydroxylases, and O-methyltransferases. This study sets the theoretical foundation for bioassay design directed at confirming the participation of these genes in mescaline production.


Assuntos
Genes de Plantas , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mescalina/biossíntese , Sophora/genética , Transcriptoma/genética , Vias Biossintéticas/genética , Descarboxilação , Di-Hidroxifenilalanina/metabolismo , Hidroxilação , Funções Verossimilhança , Mescalina/química , Metiltransferases/metabolismo , Anotação de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Sophora/enzimologia , Tirosina/metabolismo
5.
J Nat Med ; 65(1): 103-10, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20890669

RESUMO

Genus Lophophora (Cactaceae) has two species: Lophophora williamsii Coulter, which is called peyote, and L. diffusa Bravo. Although it was reported that L. williamsii contained mescaline and L. diffusa did not, we found L. williamsii specimens that did not contain mescaline. This finding indicated that the two species could not be differentiated in terms of mescaline content. Moreover, the relationship between mescaline content and morphology of the two species is also unknown. In this study, we attempted to clarify the difference in morphology, mescaline content, and DNA alignment of the chloroplast trnL/trnF region between L. williamsii and L. diffusa. As a result, L. williamsii specimens were classified into two groups. Group 1 had small protuberances on the epidermis, contained mescaline, and the analyzed region on the trnL/trnF sequence was 881 base pairs (bp) long in all except one (877 bp). Group 2 had large protuberances on the epidermis, did not contain mescaline, and the analyzed region was 893 bp long. On the other hand, L. diffusa had medium-sized protuberances on the epidermis, did not contain mescaline, and the analyzed region was 903 bp long. Also investigated was the potential application of the PCR-restriction fragment length polymorphism (RFLP) method as a means of identification based on the trnL/trnF sequence. By applying the PCR-RFLP method, the two species could be distinguished and L. williamsii specimens could be differentiated into group 1 and group 2.


Assuntos
Cactaceae/química , Cactaceae/genética , Mescalina/química , Cactaceae/ultraestrutura , Microscopia Eletrônica de Varredura , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição
6.
Analyst ; 135(6): 1449-55, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20407681

RESUMO

Electrochemical discrimination between dopamine and psychotropic drugs which have in common a skeletal structure of phenethylamine, can be obtained using acyclic receptors L(1) and L(2), containing two terminal 3-alkoxy-5-nitroindazole rings. Upon attachment to graphite electrodes, L(1) and L(2) exhibit a well-defined, essentially reversible solid state electrochemistry in contact with aqueous media, based on electrolyte-assisted reduction processes involving successive cation and anion insertion/binding. As a result, a distinctive, essentially Nernstian electrochemical response is obtained for phenethylammonium ions of methamphetamine (METH), p-methoxyamphetamine (PMA), amphetamine (AMPH), mescaline (MES), homoveratrylamine (HOM), phenethylamine (PEA) and dopamine (DA) in aqueous media.


Assuntos
Dopamina/química , Técnicas Eletroquímicas/métodos , Indazóis/química , Fenetilaminas/química , Psicotrópicos/química , Anfetamina/química , Anfetaminas/química , Carbono/química , Eletrodos , Mescalina/química , Metanfetamina/química
7.
Oxid Med Cell Longev ; 2(4): 181-90, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20716904

RESUMO

A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone counterpart. Electron transfer may play a role in electrical effects involving the nervous system in the brain. This approach is in accord with structure activity relationships involving mescaline, abused drugs, catecholamines, and etoposide. Inefficient demethylation is in keeping with the various drug properties, such as requirement for high dosage and slow acting. There is a discussion of receptor binding, electrical effects, cell signaling and other modes of action. Mescaline is a nonselective, seretonin receptor agonist. 5-HTP receptors are involved in the stimulus properties. Research addresses the aspect of stereochemical requirements. Receptor binding may involve the proposed quinone metabolite and/or the amino sidechain via protonation. Electroencephalographic studies were performed on the effects of mescaline on men. Spikes are elicited by stimulation of a cortical area. The potentials likely originate in nonsynaptic dendritic membranes. Receptor-mediated signaling pathways were examined which affect mescaline behavior. The hallucinogen belongs to the class of 2AR agonists which regulate pathways in cortical neurons. The research identifies neural and signaling mechanisms responsible for the biological effects. Recently, another hallucinogen, psilocybin, has been included within the unifying mechanistic framework. This mushroom constituent is hydrolyzed to the phenol psilocin, also active, which is subsequently oxidized to an ET o-quinone or iminoquinone.


Assuntos
Catecóis/química , Sistema Nervoso Central/efeitos dos fármacos , Mescalina/química , Agonistas do Receptor de Serotonina/química , Catecóis/metabolismo , Sistema Nervoso Central/metabolismo , Transporte de Elétrons , Mescalina/síntese química , Mescalina/farmacologia , Oxirredução , Ligação Proteica , Quinonas/química , Quinonas/metabolismo , Receptores de Serotonina/química , Receptores de Serotonina/metabolismo , Agonistas do Receptor de Serotonina/síntese química , Agonistas do Receptor de Serotonina/farmacologia , Transdução de Sinais , Relação Estrutura-Atividade
8.
Rev. neurol. (Ed. impr.) ; 42(8): 489-498, 16 abr., 2006. ilus
Artigo em Espanhol | IBECS | ID: ibc-045448

RESUMO

Introducción. El cactus de san Pedro contiene el alcaloidemescalina y otros derivados de la feniletilamina con propiedades alucinógenas. Este cactus fue usado a lo largo de la historia por diversas culturas y civilizaciones precolombinas que se asentaron en el norte del Perú. En este artículo se revisan las evidencias etnoarqueológicas y etnohistóricas sobre el uso ritual del cactus de san Pedro en las culturas precolombinas, y se comparan estos hallazgos con la información proporcionada por la etnografía actual. Desarrollo. Cuanto más tiempo haya estado almacenado un cactus, más potente y mayor contenido en alcaloides derivados dela mescalina tendrá. Se han encontrado evidencias arqueológicas del uso del san Pedro con propósitos mágico religiosos en las culturas precolombinas Cupisni que (1500 a. C.), Chavín (1000 a. C.), Moche (100-750 d. C.) y Lambayeque (750-1350 d. C.). Los maestros curanderos actuales emplean el san Pedro en mesas rituales de curación con la finalidad de tratar el hechizo y la mala suerte. La mesa tiene un sofisticado ritual: 'levantar' o esnifar tabaco con alcohol, ingerir san Pedro, adivinar las enfermedades, limpiar el mal y ‘florecer’ al enfermo. La mesa ritual se lleva a cabo de madrugada, en martes y viernes, días sagrados para la religiosidad andina. En ocasiones se sustituye el san Pedro por una infusión de plantas y semillas con componentes alucinógenos, como la ayahuasca y las mishas (Brugmansia sp.). Conclusiones. La tradición milenaria del uso curativo y alucinógeno del cactus de san Pedro ha mantenido una continuidad cultural con el curanderismo andino contemporáneo (AU)


Introduction. The San Pedro cactus contains the alkaloid mescaline and other derivates of phenethylamine with hallucinogenic properties. This cactus was used throughout history by a number of different pre-Columbine cultures and civilisations that settled in northern Peru. In this article we review the ethno-archaeological and ethno-historical evidence of the ritual use of the San Pedro cactus in the pre-Columbine cultures, and these findings are compared with the information provided by current ethnographical studies. Development. The longer a cactus has been stored, the stronger and the higher its content in mescaline-derived alkaloids will be. Archaeological evidence has been found of the use of San Pedro for magical religious purposes in the following pre-Columbine cultures: Cupisnique (1500 BC), Chavín (1000 BC), Moche (100-750 AD) and Lambayeque (750-1350 AD). Today’s master shamans use San Pedro on altars (‘mesas’) erected for healing rites in order to treat enchantment and bad luck. The mesa follows a sophisticated ritual: 'levantr' (raise) or sniff tobacco with alcohol, ingest San Pedro, pinpoint the diseases, cleanse the evil and 'florecer' (flourish) the sick person. The mesa rite is performed in the early hours of Tuesdays and Fridays, which are sacred days in the Andean religions. San Pedro is sometimes replaced by an infusion of plants and seeds that contain hallucinogenic components, such as ayahuasca and the 'mishas' (Brugmansia sp.).Conclusions. The ancient tradition of using the San Pedro cactus for healing and hallucinogenic purposes has remained part of the culture in Andean shamanism up to the present day (AU)


Assuntos
Humanos , Alucinógenos/química , Mescalina/química , Cactaceae/química , Medicina Tradicional , Etnobotânica , Antropologia Cultural
9.
Yakugaku Zasshi ; 122(4): 291-4, 2002 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-11968842

RESUMO

Four known compounds have been isolated from the aerial parts of the Brazilian medicinal plant Pariparoba (Pothomorphe umbellata). They were an alkaloid, a flavone, a dihydrocalcone, and a steroid. The chemical structures were established to be N-benzoylmescaline, wogonin, uvangoletin, and beta-sitosterol glucoside using spectral methods. Among these compounds, the main component N-benzoylmescaline showed significant antibacterial activity against Helicobacter pylori.


Assuntos
Mescalina/isolamento & purificação , Plantas Medicinais/química , Farmacorresistência Bacteriana , Helicobacter pylori/efeitos dos fármacos , Mescalina/análogos & derivados , Mescalina/química , Mescalina/farmacologia , Relação Estrutura-Atividade
10.
J Med Chem ; 40(19): 2997-3008, 1997 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-9301661

RESUMO

Dihydrobenzofuran and tetrahydrobenzodifuran functionalities were employed as conformationally restricted bioisosteres of the aromatic methoxy groups in the prototypical hallucinogen, mescaline (1). Thus, 4-(2-aminoethyl)-6,7-dimethoxy-2,3-dihydrobenzofuran hydrochloride (8) and 1-(8-methoxy-2,3,5,6-tetrahydrobenzo[1,2-b:5,4-b']difuran-4-yl)-2- aminoethane hydrochloride (9) were prepared and evaluated along with 1 for activity in the two-lever drug discrimination (DD) paradigm in rats trained to discriminate saline from LSD tartrate (0.08 mg/kg). Also, 1, 8, and 9 were assayed for their ability to displace [3H]ketanserin from rat cortical homogenate 5-HT2A receptors and [3H]8-OH-DPAT from rat hippocampal homogenate 5-HT1A receptors. In addition, these compounds were evaluated for their ability to compete for agonist and antagonist binding to cells expressing cloned human 5-HT2A, 5-HT2B, and 5-HT2C receptors. Finally, agonist efficacy was assessed by measurement of phosphoinositide hydrolysis in NIH 3T3 cells expressing the rat 5-HT2A or 5-HT2C receptors. Although 1 fully substituted for LSD in the DD assays (ED50 = 33.5 mumol/kg), neither 8 nor 9 substituted for LSD, with just 50% of the rats administered 8 selecting the drug lever, and only 29% of the rats administered 9 selecting the drug lever. All of the test compounds had micromolar affinity for the 5-HT1A and 5-HT2A receptors in rat brain homogenate. Curiously, the rank order of affinities of the compounds at 5-HT2A sites was opposite their order of potency in the behavioral assay. An evaluation for ability to stimulate phosphoinositide turnover as a measure of functional efficacy revealed that all the compounds were of approximately equal efficacy to serotonin in 5-HT2C receptors. At 5-HT2A receptors, however, 8 and 9 were significantly less efficacious, eliciting only 61 and 45%, respectively, of the maximal response. These results are consistent with the proposed mechanism of action for phenethylamine hallucinogens, that such compounds must be full agonists at the 5-HT2A receptor subtype. In contrast to the 2,5-dimethoxy-substituted phenethylamines, where rigidification of the methoxy groups had no deleterious effect on activity, the loss of activity in the 3,4,5-trioxygenated mescaline analogues may suggest that the 3 and 5 methoxy groups must remain conformationally mobile to enable receptor activation.


Assuntos
Benzofuranos/síntese química , Alucinógenos/síntese química , Mescalina/análogos & derivados , Mescalina/síntese química , Células 3T3 , Animais , Benzofuranos/química , Benzofuranos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Alucinógenos/química , Alucinógenos/farmacologia , Humanos , Indicadores e Reagentes , Dose Letal Mediana , Dietilamida do Ácido Lisérgico/análogos & derivados , Dietilamida do Ácido Lisérgico/síntese química , Dietilamida do Ácido Lisérgico/química , Dietilamida do Ácido Lisérgico/farmacologia , Mescalina/química , Mescalina/farmacologia , Camundongos , Estrutura Molecular , Fosfatidilinositóis/metabolismo , Ensaio Radioligante , Ratos , Receptor 5-HT2A de Serotonina , Receptor 5-HT2C de Serotonina , Receptores de Serotonina/efeitos dos fármacos , Receptores de Serotonina/fisiologia , Proteínas Recombinantes/efeitos dos fármacos , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade , Transfecção
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