2018 |
Cassels, B K; Saez-Briones, P Dark Classics in Chemical Neuroscience: Mescaline Artículo de revista Acs Chemical Neuroscience, 9 (10), pp. 2448-2458, 2018, ISSN: 1948-7193. Resumen | Enlaces | BibTeX | Etiquetas: analogs, biosynthesis, cancer, derivatives, diethylamide, hallucinogen, hallucinogenic life-threatening lysergic-acid mescaline, metabolism, pedro, peyote, pharmacology, phenethylamine, phenyl-aethylamine, properties, relationships, san serotonin stimulus structure-activity synthesis, wachuma @article{RN389, title = {Dark Classics in Chemical Neuroscience: Mescaline}, author = { B.K. Cassels and P. Saez-Briones}, url = {/brokenurl#<Go to ISI>://WOS:000447954300015}, doi = {10.1021/acschemneuro.8b00215}, issn = {1948-7193}, year = {2018}, date = {2018-01-01}, journal = {Acs Chemical Neuroscience}, volume = {9}, number = {10}, pages = {2448-2458}, abstract = {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 alpha(2A) 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.}, keywords = {analogs, biosynthesis, cancer, derivatives, diethylamide, hallucinogen, hallucinogenic life-threatening lysergic-acid mescaline, metabolism, pedro, peyote, pharmacology, phenethylamine, phenyl-aethylamine, properties, relationships, san serotonin stimulus structure-activity synthesis, wachuma}, pubstate = {published}, tppubtype = {article} } 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 alpha(2A) 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. |
2013 |
Faundez-Parraguez, M; Farias-Rabelo, N; González-Gutierrez, J P; Etcheverry-Berrios, A; Alzate-Morales, J; Adasme-Carreno, F; Varas, R; Bermudez, I; Iturriaga-Vasquez, P Neonicotinic Analogues: Selective Antagonists for Alpha 4 Beta 2 Nicotinic Acetylcholine Receptors Artículo de revista Bioorganic & Medicinal Chemistry, 21 (10), pp. 2687-2694, 2013, ISSN: 0968-0896. Resumen | Enlaces | BibTeX | Etiquetas: agonists, and antagonism, beta-2 binding, cytisine, docking functional modulators, nicotinic receptors, relationships, sensitivity, structure-activity subunit @article{RN130, title = {Neonicotinic Analogues: Selective Antagonists for Alpha 4 Beta 2 Nicotinic Acetylcholine Receptors}, author = { M. Faundez-Parraguez and N. Farias-Rabelo and J.P. Gonz\'{a}lez-Gutierrez and A. Etcheverry-Berrios and J. Alzate-Morales and F. Adasme-Carreno and R. Varas and I. Bermudez and P. Iturriaga-Vasquez}, url = {/brokenurl#<Go to ISI>://WOS:000318318700003}, doi = {10.1016/j.bmc.2013.03.024}, issn = {0968-0896}, year = {2013}, date = {2013-01-01}, journal = {Bioorganic & Medicinal Chemistry}, volume = {21}, number = {10}, pages = {2687-2694}, publisher = {2013 Elsevier Ltd.}, abstract = {Nicotine is an agonist of nicotinic acetylcholine receptors (nAChRs) that has been extensively used as a template for the synthesis of alpha 4 beta 2-preferring nAChRs. Here, we used the N-methyl-pyrrolidine moiety of nicotine to design and synthesise novel alpha 4 beta 2-preferring neonicotinic ligands. We increased the distance between the basic nitrogen and aromatic group of nicotine by introducing an ester functionality that also mimics acetylcholine (Fig. 2). Additionally, we introduced a benzyloxy group linked to the benzoyl moiety. Although the neonicotinic compounds fully inhibited binding of both [alpha-I-125]bungarotoxin to human alpha 7 nAChRs and [H-3]cytisine to human alpha 4 beta 2 nAChRs, they were markedly more potent at displacing radioligand binding to human alpha 4 beta 2 nAChRs than to alpha 7 nAChRs. Functional assays showed that the neonicotinic compounds behave as antagonists at alpha 4 beta 2 and alpha 4 beta 2 alpha 5 nAChRs. Substitutions on the aromatic ring of the compounds produced compounds that displayed marked selectivity for alpha 4 beta 2 or alpha 4 beta 2 alpha 5 nAChRs. Docking of the compounds on homology models of the agonist binding site at the alpha 4/beta 2 subunit interfaces of alpha 4 beta 2 nAChRs suggested the compounds inhibit function of this nAChR type by binding the agonist binding site.}, keywords = {agonists, and antagonism, beta-2 binding, cytisine, docking functional modulators, nicotinic receptors, relationships, sensitivity, structure-activity subunit}, pubstate = {published}, tppubtype = {article} } Nicotine is an agonist of nicotinic acetylcholine receptors (nAChRs) that has been extensively used as a template for the synthesis of alpha 4 beta 2-preferring nAChRs. Here, we used the N-methyl-pyrrolidine moiety of nicotine to design and synthesise novel alpha 4 beta 2-preferring neonicotinic ligands. We increased the distance between the basic nitrogen and aromatic group of nicotine by introducing an ester functionality that also mimics acetylcholine (Fig. 2). Additionally, we introduced a benzyloxy group linked to the benzoyl moiety. Although the neonicotinic compounds fully inhibited binding of both [alpha-I-125]bungarotoxin to human alpha 7 nAChRs and [H-3]cytisine to human alpha 4 beta 2 nAChRs, they were markedly more potent at displacing radioligand binding to human alpha 4 beta 2 nAChRs than to alpha 7 nAChRs. Functional assays showed that the neonicotinic compounds behave as antagonists at alpha 4 beta 2 and alpha 4 beta 2 alpha 5 nAChRs. Substitutions on the aromatic ring of the compounds produced compounds that displayed marked selectivity for alpha 4 beta 2 or alpha 4 beta 2 alpha 5 nAChRs. Docking of the compounds on homology models of the agonist binding site at the alpha 4/beta 2 subunit interfaces of alpha 4 beta 2 nAChRs suggested the compounds inhibit function of this nAChR type by binding the agonist binding site. |
2018 |
Dark Classics in Chemical Neuroscience: Mescaline Artículo de revista Acs Chemical Neuroscience, 9 (10), pp. 2448-2458, 2018, ISSN: 1948-7193. |
2013 |
Neonicotinic Analogues: Selective Antagonists for Alpha 4 Beta 2 Nicotinic Acetylcholine Receptors Artículo de revista Bioorganic & Medicinal Chemistry, 21 (10), pp. 2687-2694, 2013, ISSN: 0968-0896. |